s-1743 and Gastroesophageal-Reflux

Gastro-oesophageal reflux (GOR) is characterised by the regurgitation of gastric contents into the oesophagus. GOR is a common presentation in infancy, both in primary and secondary care, affecting approximately 50% of infants under three months old. The natural history of GOR in infancy is generally of a self-limiting condition that improves with age, but older children and children with co-existing medical conditions can have more protracted symptoms. The distinction between gastro-oesophageal reflux disease (GORD) and GOR is debated. Current National Institute of Health and Care Excellence (NICE) guidelines define GORD as GOR causing symptoms severe enough to merit treatment. This is an update of a review first published in 2014.. To assess the effects of pharmacological treatments for GOR in infants and children.. For this update, we searched CENTRAL, MEDLINE, Embase, and Web of Science up to 17 September 2022. We also searched for ongoing trials in clinical trials registries, contacted experts in the field, and searched the reference lists of trials and reviews for any additional trials.. We included randomised controlled trials (RCTs) that compared any currently-available pharmacological treatment for GOR in children with placebo or another medication. We excluded studies assessing dietary management of GORD and studies of thickened feeds. We included studies in infants and children up to 16 years old.. We used standard methodology expected by Cochrane.. We included 36 RCTs involving 2251 children and infants. We were able to extract summary data from 14 RCTs; the remaining trials had insufficient data for extraction. We were unable to pool results in a meta-analysis due to methodological differences in the included studies (including heterogeneous outcomes, study populations, and study design). We present the results in two groups by age: infants up to 12 months old, and children aged 12 months to 16 years old. Infants Omeprazole versus placebo: there is no clear effect on symptoms from omeprazole. One study (30 infants; very low-certainty evidence) showed cry/fuss time in infants aged three to 12 months had altered from 246 ± 105 minutes/day at baseline (mean +/- standard deviation (SD)) to 191 ± 120 minutes/day in the omeprazole group and from 287 ± 132 minutes/day to 201 ± 100 minutes/day in the placebo group (mean difference (MD) 10 minutes/day lower (95% confidence interval (CI) -89.1 to 69.1)). The reflux index changed in the omeprazole group from 9.9 ± 5.8% in 24 hours to 1.0 ± 1.3% and in the placebo group from 7.2 ± 6.0% to 5.3 ± 4.9% in 24 hours (MD 7% lower, 95% CI -4.7 to -9.3). Omeprazole versus ranitidine: one study (76 infants; very low-certainty evidence) showed omeprazole may or may not provide symptomatic benefit equivalent to ranitidine. Symptom scores in the omeprazole group changed from 51.9 ± 5.4 to 2.4 ± 1.2, and in the ranitidine group from 47 ± 5.6 to 2.5 ± 0.6 after two weeks: MD -4.97 (95% CI -7.33 to -2.61). Esomeprazole versus placebo: esomeprazole appeared to show no additional reduction in the number of GORD symptoms compared to placebo (1 study, 52 neonates; very low-certainty evidence): both the esomeprazole group (184.7 ± 78.5 to 156.7 ± 75.1) and placebo group (183.1 ± 77.5 to 158.3 ± 75.9) improved: MD -3.2 (95% CI -4.6 to -1.8). Children Proton pump inhibitors (PPIs) at different doses may provide little to no symptomatic and endoscopic benefit. Rabeprazole given at different doses (0.5 mg/kg and 1 mg/kg) may provide similar symptom improvement (127 children in total; very low-certainty evidence). In the lower-dose group (0.5 mg/kg), symptom scores improved in both a low-weight group of children (< 15 kg) (mean -10.6 ± SD 11.13) and a high-weight group of children (> 15 kg) (mean -13.6 ± 13.1). In the higher-dose groups (1 mg/kg), scores improved in the low-weight (-9 ± 11.2) and higher-weight groups (-8.3 ± 9.2). For the higher-weight group, symptom score mean differ. There is very low-certainty evidence about symptom improvements and changes in pH indices for infants. There are no summary data for endoscopic changes. Medications may or may not provide a benefit (based on very low-certainty evidence) for infants whose symptoms remain bothersome, despite nonmedical interventions or parental reassurance. If a medication is required, there is no clear evidence based on summary data for omeprazole, esomeprazole (in neonates), H₂antagonists, and alginates for symptom improvements (very low-certainty evidence). Further studies with longer follow-up are needed. In older children with GORD, in studies with summary data extracted, there is very low-certainty evidence that PPIs (rabeprazole and pantoprazole) may or may not improve GORD outcomes. No robust data exist for other medications. Further RCT evidence is required in all areas, including subgroups (preterm babies and children with neurodisabilities).

Topics: Adolescent; Child; Esomeprazole; Gastroesophageal Reflux; Humans; Infant; Infant, Newborn; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Ranitidine

The introduction of acid inhibition in clinical practice has revolutionized the management of acid-related diseases, leading to the virtual abolition of elective surgery for ulcer disease and relegating antireflux surgery to patients with gastroesophageal reflux disease (GERD) not adequately managed by medical therapy. Proton pump inhibitors (PPIs) are the antisecretory drugs of choice for the treatment of reflux disease. However, these drugs still leave some unmet clinical needs in GERD. PPI-refractoriness is common, and persistent symptoms are observed in up to 40-55% of daily PPI users. Potassium-competitive acid blockers (P-CABs) clearly overcome many of the drawbacks and limitations of PPIs, achieving rapid, potent, and prolonged acid suppression, offering the opportunity to address many of the unmet needs. In recent years, it has been increasingly recognized that impaired mucosal integrity is involved in the pathogenesis of GERD. As a consequence, esophageal mucosal protection has emerged as a new, promising therapeutic avenue. When P-CABS are used as add-on medications to standard treatment, a growing body of evidence suggests a significant additional benefit, especially in the relief of symptoms not responding to PPI therapy. On the contrary, reflux inhibitors are considered a promise unfulfilled, and prokinetic agents should only be used on a case-by-case basis.

Topics: Cimetidine; Esomeprazole; Esophageal Mucosa; Gastroesophageal Reflux; Humans; Lansoprazole; Omeprazole; Proton Pump Inhibitors; Pyrroles; Sulfonamides

Proton pump inhibitors (PPIs) are one of the most frequently prescribed medications across the globe. Esomeprazole is the S-isomer of omeprazole, and it is currently the most widely prescribed PPI. The safety profile of esomeprazole is extremely favorable with only minor side effects, like headache and diarrhea, that are encountered in day to day practice. We report a case of a young female with symptoms of gastroesophageal reflux disease who developed galactorrhea after starting esomeprazole therapy. Resolution of galactorrhea after stopping the drug and self-rechallenge by the patient herself with reappearance of galactorrhea confirmed the culprit to be esomeprazole only. We postulate that esomeprazole may have a mild inhibitory effect on CYP3A4, which leads to decreased metabolism of estrogen, thereby increasing serum estrogen levels. Estrogen causes stimulation and production of prolactin release, which results in development of galactorrhea. This is the first case of esomeprazole induced galactorrhea, to the best of our knowledge.

Topics: Adult; Amenorrhea; Esomeprazole; Female; Galactorrhea; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors

To compare the cost-effectiveness of therapy of gastroesophageal reflux disease with esomeprazole and other proton pump inhibitors (PPIs) in Poland.. Studies comparing esomeprazole with other PPIs in the treatment of erosive esophagitis, non-erosive reflux disease and gastroesophageal reflux disease maintenance therapy were systematically reviewed. 9 randomized clinical trials were selected, meta-analyses were conducted. Cost data derived from Polish Ministry of Health and Pharmacies in Wroclaw.. In the treatment of erosive esophagitis esomeprazole was significantly more effective than other PPIs. Both for 4- and 8-week therapy respective incremental cost-effectiveness ratio values were acceptably low. Differences in effectiveness of non-erosive reflux disease therapy were not significant. The replacement of pantoprazole 20 mg with more effective esomeprazole 20 mg in the 6-month maintenance therapy was associated with a substantially high incremental cost-effectiveness ratio.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Cost-Benefit Analysis; Esomeprazole; Gastroesophageal Reflux; Humans; Pantoprazole; Poland; Proton Pump Inhibitors; Treatment Outcome

Dose selection is one of the key decisions made during drug development in pediatrics. There are regulatory initiatives that promote the use of model-based drug development in pediatrics. Pharmacometrics or quantitative clinical pharmacology enables development of models that can describe factors affecting pharmacokinetics and/or pharmacodynamics in pediatric patients. This manuscript describes some examples in which pharmacometric analysis was used to support approval and labeling in pediatrics. In particular, the role of pharmacokinetic (PK) comparison of pediatric PK to adults and utilization of dose/exposure-response analysis for dose selection are highlighted. Dose selection for esomeprazole in pediatrics was based on PK matching to adults, whereas for adalimumab, exposure-response, PK, efficacy, and safety data together were useful to recommend doses for pediatric Crohn's disease. For vigabatrin, demonstration of similar dose-response between pediatrics and adults allowed for selection of a pediatric dose. Based on model-based pharmacokinetic simulations and safety data from darunavir pediatric clinical studies with a twice-daily regimen, different once-daily dosing regimens for treatment-naïve human immunodeficiency virus 1-infected pediatric subjects 3 to <12 years of age were evaluated. The role of physiologically based pharmacokinetic modeling (PBPK) in predicting pediatric PK is rapidly evolving. However, regulatory review experiences and an understanding of the state of science indicate that there is a lack of established predictive performance of PBPK in pediatric PK prediction. Moving forward, pharmacometrics will continue to play a key role in pediatric drug development contributing toward decisions pertaining to dose selection, trial designs, and assessing disease similarity to adults to support extrapolation of efficacy.

Topics: Adalimumab; Adolescent; Adolescent Development; Adult; Age Factors; Anti-HIV Agents; Anti-Inflammatory Agents; Anticonvulsants; Child; Child Development; Child, Preschool; Crohn Disease; Dose-Response Relationship, Drug; Drug Approval; Drug Dosage Calculations; Drug Labeling; Esomeprazole; Gastroesophageal Reflux; HIV Infections; Humans; Infant; Infant, Newborn; Models, Biological; Pharmaceutical Preparations; Pharmacokinetics; Proton Pump Inhibitors; Seizures; Vigabatrin

Here we aimed to evaluate the effectiveness of esomeprazole treatment strategies comparing with other proton pump inhibitors (PPI) in clinical practice for six months in the management of patients with symptomatic gastroesophageal reflux disease (GERD). An extensive search of the literature focusing on PPI therapeutic evaluation was performed up to December 2014. Risk ratio (RR) with its corresponding 95% confidence intervals (CIs) in each study was chosen as the effect size. Cochrane's Q statistic and I2 test were both conducted to evaluate heterogeneity across individual studies. Meta-regression was conducted to explore the source of heterogeneity and sensitive analysis was performed to assess the risk bias for the meta-analysis. Totally, eleven trials with high quality enrolled in the meta-analysis. Esomeprazole therapy (20 mg daily) had lower relapse rates than other drugs during six months maintenance treatment (RR = 0.67; 95% CI: 0.55-0.83). Heartburn (RR = 0.72; 95% CI: 0.57-0.92) and epigastric pain (RR = 0.82, 95% Cl: 0.70-0.96) were less likely to happen after esomeprazole treatment, and no significant advantage was found on acid regurgitation and dysphagia. Moreover, lower risk for serious adverse events was observed after esomeprazole therapy (RR = 1.40, 95% CI: 1.04-1.88). Blind method or difference controlled drugs did not influence heterogeneity across studies. Moreover, the conclusion on acid regurgitation, abdominal pain and dysphagia might be unstable. In GERD patients, esomeprazole 20 mg daily is more effective than other PPIs regarding relapse rates, symptoms of epigastric pain and heartburn, and serious adverse events.

Topics: Abdominal Pain; Deglutition Disorders; Esomeprazole; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Recurrence; Regression Analysis

Proton pump inhibitors (PPIs) are one of the most widely used classes of drugs. However, the quantum clinical benefit of newer and more expensive PPIs over the older generation PPIs remains uncertain. This meta-analysis sought to assess the clinical and safety profiles of esomeprazole versus omeprazole at pharmacologically equivalent doses in healing gastroesophageal reflux disease (GERD), peptic ulcer disease and eradicating Helicobacter pylori (H. pylori) infection.. PubMed and the Cochrane Library were searched for randomized controlled trials comparing esomeprazole with omeprazole at all doses up to February 2015. Trials were assessed by two reviewers for eligibility according to predefined study inclusion criteria. Meta-analysis was conducted using a random effects model, and heterogeneity in the estimated effects was investigated using meta-regression. Sensitivity analysis was performed to test the robustness of the findings.. Fifteen trials were included and none of which compared esomeprazole with omeprazole in peptic ulcer disease. The included studies had not evaluated esomeprazole 20 mg versus omeprazole 40 mg. In GERD, esomeprazole 40 mg (relative risk (RR) = 1·07; 95% confidence interval (CI) 1·02 to 1·12) and 20 mg (RR=1·04; 95% CI 1·01 to 1·08) significantly improved esophagitis healing when compared with omeprazole 20 mg at week 8. The corresponding numbers needed to treat were 17 and 30, respectively. No significant difference was observed between esomeprazole 20 mg and omeprazole 20 mg at week 4. In H. pylori eradication, there was no difference in the treatment effects between esomeprazole 20 mg and omeprazole 20 mg (RR = 1·01;95% CI 0·96 to 1·05). Their safety profiles were comparable.. Esomeprazole demonstrated better esophagitis healing rate in patients with GERD than omeprazole at week 8. However, this clinical advantage diminished when both drugs were given at the same doses at week 4. Superiority of esomeprazole was not observed in the H. pylori eradication rates.

Topics: Esomeprazole; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole; Proton Pump Inhibitors; Randomized Controlled Trials as Topic

This study aims to evaluate the effectiveness and tolerability of esomeprazole and omeprazole in patients with gastroesophageal reflux disease (GERD). Electronic searches on PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov databases were carried out for reports up to February 28, 2015. Ten eligible studies from 8 articles were found that enrolled a total of 10,286 patients for meta-analysis. These results revealed a significant difference between esomeprazole vs. omeprazole (RR=1.06, 95% CI [1.01, 1.10], I2=72%, p=0.01) by subgroup according to dosage by random effects model, and a significant difference between esomeprazole 40 mg vs. omeprazole 20 mg (RR=1.07, 95% CI [1.004, 1.14], I2=78%, p=0.04) based on healing rate as determined by endoscopy, using a random effects model. A significant difference between esomeprazole 20 mg and omeprazole 40 mg (RR=0.68, 95% CI [0.47, 0.97], I2=not applicable, p=0.03) was also found in comparing relief of symptoms by random effects model. There were no significant differences in outcomes between other subgroups, including tolerability. Based on these results, a high dose of esomeprazole is recommended for GERD treatment and control in adults.

Topics: Esomeprazole; Gastroesophageal Reflux; Humans; Omeprazole; Proton Pump Inhibitors; Publication Bias

The prevalence of gastroesophageal reflux disease continues to increase with the aging population and the obesity epidemic. Therapeutic failures can have significant detrimental effects in patients. Recently, dexlansoprazole MR and esomeprazole strontium were introduced to the class of proton pump inhibitors (PPIs).. This article will review the pharmacodynamics and pharmacokinetics of dexlansoprazole MR and esomeprazole strontium. Using the keywords 'dexlansoprazole MR' and 'esomeprazole strontium' in the search engines of PubMed, Cochrane Reviews and Google, we were able to identify peer-reviewed publications, abstracts and presentations at national society educations meetings and present a balanced view of the available data.. Dexlansoprazole MR and esomeprazole strontium offer an innovative delivery mechanism compared to conventional PPIs. Further trials are necessary in order to establish superiority.

Topics: Administration, Oral; Animals; Clinical Trials as Topic; Dexlansoprazole; Drug Evaluation, Preclinical; Esomeprazole; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Treatment Outcome

Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related diseases such as gastroesophageal reflux disease (GERD). They are recommended by the American College of Gastroenterology for healing erosive esophagitis (EO) and as long-term treatment in patients with healed EO. The available PPIs differ somewhat in their pharmacokinetics and clinical properties, but whether these differences are of clinical relevance is a matter of debate. Some safety concerns have been raised with the use of PPIs, mostly an increased incidence of infectious diseases such as community-acquired pneumonia or Clostridium difficile diarrhea.. This article explores the results of clinical studies on the pharmacokinetics and pharmacodynamics of esomeprazole , as well as on its clinical efficacy to manage patients with GERD.. GERD is a public health concern as its worldwide incidence and associated complications are increasing alongside the exponentially increasing problem of obesity. PPIs are the first pharmacological option because of their efficacy and overall positive risk-to-benefit ratio. Improved efficacy with the use of stereospecific isomers of PPIs, such as esomeprazole, has not yet been convincingly demonstrated. Nevertheless, because of individual experience with former treatment, some patients may report better symptom control when treated with a specific PPI rather than with others.

Topics: Esomeprazole; Esophagitis; Gastroesophageal Reflux; Humans; Incidence; Proton Pump Inhibitors; Stereoisomerism

Topics: Anti-Ulcer Agents; Combined Modality Therapy; Diagnosis, Differential; Dietary Carbohydrates; Dumping Syndrome; Esomeprazole; Female; Fundoplication; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Hormones; Humans; Hypoglycemia; Insulinoma; Postprandial Period; Young Adult

Peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD) are not uncommon in elderly patients. Clinical presentations of these acid-related disorders may be atypical in the geriatric population. Older individuals are at increased risk for poor outcomes in complicated PUD and for development of GERD complications. Multiple risk factors (eg, Helicobacter pylori [HP], use of nonsteroidal anti-inflammatory drugs [NSAIDs], aspirin) contribute to the development of PUD. Recent data has shown that HP-negative, NSAID-negative idiopathic peptic ulcers are on the rise and carry a higher risk of recurrent ulcer bleeding and mortality. Effective management of PUD in the geriatric population relies on identification and modification of treatable risk factors. Elderly patients with GERD often require long-term acid suppressive therapy. Proton pump inhibitors (PPI) including esomeprazole are effective in the treatment of reflux esophagitis, maintenance of GERD symptomatic control, and management of PUD as well as its complications. Potential safety concerns of long-term PPI use have been reported in the literature. Clinicians should balance the risks and benefits before committing elderly patients to long-term PPI therapy.

Topics: Aged; Anti-Ulcer Agents; China; Esomeprazole; Female; Gastroesophageal Reflux; Hong Kong; Humans; Male; Peptic Ulcer

Proton pump inhibitors (PPIs) are the most potent inhibitors of gastric acid secretion available, and they are effective for treating all acid-related disorders. Esomeprazole is one of several most recent PPIs that became available to the market in 2001. Esomeprazole is indicated for the treatment of gastroesophageal reflux disease in adults and children, risk reduction of NSAIDs-associated gastric ulcer, Helicobacter pylori eradication and control of pathological hypersecretory conditions associated with Zollinger-Ellison syndrome. Esomeprazole is available in both oral and intravenous formulations. A number of studies have compared esomeprazole with other PPIs. While differences supporting esomeprazole have been reported, the magnitude of differences has been variable and of uncertain clinical importance. Cost plays a major role in prescribing patterns of PPIs.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Drug Costs; Esomeprazole; Gastroesophageal Reflux; Helicobacter Infections; Humans; Proton Pump Inhibitors; Stomach Ulcer

Esomeprazole (Nexium); S-omeprazole) is a single optical isomer proton-pump inhibitor (PPI) approved for the management of reflux oesophagitis, the symptomatic treatment of gastro-oesophageal reflux disease (GORD), the prevention and healing of NSAID-associated gastric ulcer disease (and the prevention of NSAID-associated duodenal ulcers in the UK), the treatment of Helicobacter pylori infection and associated duodenal ulcer disease (and prevention of relapse of H. pylori-associated peptic ulcers in the UK), and the treatment of Zollinger-Ellison syndrome (and other hypersecretory syndromes in the US).Once-daily oral esomeprazole 40 mg demonstrates greater antisecretory activity than other PPIs. Overall, in well designed clinical studies of 4 weeks' to 6 months' duration in patients with GORD, esomeprazole had similar or better efficacy than other agents. In patients requiring ongoing treatment with NSAIDs, co-therapy with once-daily esomeprazole 20 or 40 mg achieved relief of gastrointestinal symptoms or prevented ulcer occurrence, more effectively than placebo. Esomeprazole was also better than ranitidine 150 mg twice daily in healing NSAID-associated gastric ulcers. In addition, the drug has demonstrated efficacy as part of a triple-therapy regimen for the eradication of H. pylori infection, the healing of H. pylori associated duodenal ulcers and the prevention of relapse of gastric ulcers. Esomeprazole also effectively treated patients with Zollinger-Ellison syndrome. Esomeprazole is generally well tolerated with an adverse-event profile similar to that of other PPIs. Thus, the efficacy and tolerability of esomeprazole for the management of GORD and H. pylori eradication remains undisputed, and the data support its use for the first-line treatment of NSAID-associated gastric ulcer disease and Zollinger-Ellison syndrome.

Topics: Adult; Anti-Ulcer Agents; Duodenal Ulcer; Esomeprazole; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole; Proton Pump Inhibitors; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Adolescent; Anti-Ulcer Agents; Child; Child, Preschool; Drug Interactions; Esomeprazole; Gastroesophageal Reflux; Humans; Infant; Intestinal Absorption; Treatment Outcome

The use of non-steroidal anti-inflammatory drugs (NSAIDs) is often associated with upper gastrointestinal symptoms such as heartburn and acid regurgitation.. To assess the efficacy of esomeprazole 20 and 40 mg for resolution of heartburn and acid regurgitation in continuous NSAIDs.. A post hoc analysis of five clinical trials was performed. Two identically designed, placebo-controlled, 4-week studies (NASA1, SPACE1) enrolled non-ulcer, NSAIDs-treated patients with upper abdominal pain, discomfort or burning. PLUTO and VENUS were identically designed, placebo-controlled, 6-month studies that enrolled patients at risk of NSAIDs-induced ulcers. Study 285 was an 8-week comparative study with ranitidine (300 mg/day) in patients with NSAIDs-induced gastric ulcers. Resolution of investigator-assessed heartburn and acid regurgitation was defined as symptom severity of 'none' in the last 7 days.. In NASA1/SPACE1, heartburn resolved in 61% and 62% of patients taking esomeprazole 20 and 40 mg, respectively (vs. 36% on placebo, P < 0.001), and acid regurgitation resolved in 65% and 67% (vs. 48%, P < 0.001). Resolution of both symptoms was greater with esomeprazole than with placebo in PLUTO/VENUS (P

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Esomeprazole; Female; Gastroesophageal Reflux; Heartburn; Humans; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Treatment Outcome

Proton pump inhibitors (PPI) are characterized by high effectiveness, selectivity and few adverse events. Development of PPI was an important issue in aspect of acid-related diseases treatment. Nowadays following PPI are available on the market: omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole. In children these drugs are the most frequently use in gastritis and duodenitis, ulcer disease with coexistence of Helicobacter pylori infection and gastroesophageal reflux disease. Pharmacokinetics of PPI is slightly different in children than in adults and so far there is a lack of randomised studies assessing the efficacy of PPI i developmental period medicine on numerous groups of patients. In our study literature review of PPI use in children and youth was presented.

Topics: Adult; Age Factors; Anti-Ulcer Agents; Child; Drug Interactions; Duodenitis; Enzyme Inhibitors; Esomeprazole; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Humans; Omeprazole; Peptic Ulcer; Proton Pump Inhibitors

Gastro-oesophageal reflux disease (GORD) is associated with a broad array of symptoms that may be typical or atypical of the disease and that may be accompanied by erosive oesophagitis. Symptom scales that have historically been employed to assess response to treatment in GORD clinical trials do not typically account for the heterogeneous, episodic nature of GORD and the poor correlation between patients' and physicians' assessment of symptoms. The ReQuest questionnaire permits self-assessment of changes on a broad range of GORD-related symptoms on a daily basis and in combination with the Los Angeles (LA)-classification (ReQuest/LA-classification) to assess complete remission of GORD. Pantoprazole and esomeprazole are two of the newer proton pump inhibitors and are the first to be systematically reviewed using the ReQuest(trade mark) questionnaire. Results from recent head-to-head trials have shown pantoprazole and esomeprazole to be highly and equally effective treatments for (i) rapid and sustained relief of ReQuest-assessed GORD-related symptoms in patients with non-erosive GORD or endoscopically confirmed erosive GORD, and (ii) achieving a combined outcome comprising endoscopically confirmed healing and ReQuest-assessed symptom relief in patients with erosive GORD. There is some preliminary evidence to suggest that pantoprazole may be the better choice of treatment in terms of its potential to maintain control of symptoms in patients for whom night-time symptoms are a concern and if taken as on-demand rather than continuous maintenance therapy.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Databases, Factual; Esomeprazole; Gastroesophageal Reflux; Humans; Pantoprazole; Proton Pump Inhibitors; Psychometrics; Reproducibility of Results; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Proton pump inhibitors (PPIs) are antisecretory agents that are widely used in the short- and long-term management of gastroesophageal reflux disease (GERD) to relieve symptoms, heal esophagitis, and prevent complications, such as strictures and Barrett's esophagus. The total healthcare costs of GERD are high, especially for maintenance treatment. Therefore, the choice of cost-effective therapeutic options is an ineluctable challenge for public health authorities, third-party payers, and patients. In some European Union countries, a recent trend of public health authorities is to promote the choice of less expensive PPIs, regardless of their antisecretory potency--this in spite of the evidence that newer PPIs provide superior symptom relief and esophageal erosion healing compared to earlier drugs. Several large clinical trials have demonstrated the superiority of esomeprazole over other PPIs at standard doses for both initial and continuous maintenance therapy in patients with moderate/severe erosive esophagitis. The non-erosive GERD poses a major challenge as this condition appears more frequently to be less responsive to PPIs. The use of PPIs with the strongest antisecretory properties might reveal to be more adequate and cost-effective, particularly for this indication.

Topics: Esomeprazole; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Randomized Controlled Trials as Topic

Chirality is a ubiquitous natural phenomenon resulting because of a differential spatial orientation of molecules around its chiral centre. This leads to the existence of two or more spatially dissimilar forms, known as stereoisomers or enantiomers, which are non-superimposable images of each other and may significantly differ from each other with respect to pharmacokinetic and pharmacodynamic properties and molecular interaction. Thus one isomer may offer significant pharmacokinetic and therapeutic advantages as compared to the other isomer or the racemic mixture (mixture containing both enantiomers). Proton pump inhibitors are a class of drugs which have been very effective in the management of acid-related disorders. The proton pumps currently available in the market including omeprazole, pantoprazole, rabeprazole and lansoprazole are racemic mixtures of the S and R isomers. Chirally pure forms of proton pump inhibitors show a superior metabolic and pharmacokinetic profile as compared to their racemates. The therapeutic efficacy is also superior to the parent racemate. This has been clearly demonstrated with the development of esomeprazole- the S-isomer of omeprazole. S-pantoprazole and dexrabeprazole also offer therapeutic advantages as compared to racemic pantoprazole and racemic rabeprazole respectively. This article reviews the chiral developments in the proton pump inhibitors and their clinical applications.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Esomeprazole; Gastroesophageal Reflux; Humans; Isomerism; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole

Patients who complain of symptoms of gastro-oesophageal reflux disease (GORD) that occur at night require special attention. Night-time GORD can profoundly impair quality of life by causing pain, disturbing sleep, and interfering with next-day mental and physical functioning. Sleep impairs oesophageal acid clearance resulting in a prolongation of acid mucosal contact, and nocturnal reflux portends a greater risk of erosive oesophagitis and other significant complications of gastro-oesophageal reflux. Lifestyle changes such as elevating the head of the bed and adjusting the sleeping position can relieve night-time heartburn, and instituting some dietary changes along with occasional use of histamine H2 blockers can also be helpful. Relief of night-time reflux and its attendant symptoms usually requires a medication with acid-suppressing properties that extend into the sleeping interval. In most instances, more powerful acid suppression in the form of proton-pump inhibitors will be required. Clinical studies have shown that 40 mg esomeprazole provides better control of night-time GORD symptoms than 20 mg omeprazole or 30 mg lansoprazole. Furthermore, 40 mg pantoprazole offers even faster relief than 40 mg esomeprazole for night-time GORD symptoms. Of the several proton-pump inhibitors available on the market, esomeprazole and pantoprazole appear to have some advantages, which have been documented in recent studies. Esomeprazole has been shown to be more effective than lansoprazole in relieving GORD symptoms, and esomeprazole and pantoprazole appear to be equally effective in resolving GORD symptoms in a comparative study. Pantoprazole has pharmacokinetic properties that document a longer half-life compared with the other proton-pump inhibitors, and pantoprazole has the slowest inhibition recovery rate. These properties lend credence to pantoprazole as an effective treatment for associated symptoms of night-time reflux.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Circadian Rhythm; Esomeprazole; Gastroesophageal Reflux; Humans; Omeprazole; Pantoprazole; Prevalence; Proton Pump Inhibitors; Sulfoxides

Lansoprazole is an H+, K+-adenosine triphosphatase proton pump inhibitor (PPI) used for management of acid-related disorders. Lansoprazole has been reformulated as an oro-dispersible tablet (LODT) that quickly dissolves in the mouth without water. In healthy adults the safety and bioavailability of LODT 15-30 mg, taken without water or dispersed in water, were found to be comparable with those of lansoprazole 15-30 mg capsules. Moreover, the bioavailability of LODT administered without water has been found to be similar to that of water-dispersed LODT given via a nasogastric tube. In a clinical study, the vast majority of patients found the mouth feel of LODT acceptable and almost all found it easy to take. A comparison of LODT with esomeprazole in a small group of patients with non-erosive reflux disease showed similar decreases in symptoms from baseline and no significant difference between groups. In conclusion, LODT is effective, bioequivalent to the capsule formulation and acceptable to patients. LODT offers an alternative dose administration method to all patients requiring a PPI, especially those who have difficulty swallowing, and may increase patient convenience and compliance.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Esomeprazole; Gastroesophageal Reflux; Humans; Lansoprazole; Proton Pump Inhibitors; Tablets; Technology, Pharmaceutical; Treatment Outcome

Proton pump inhibitors (PPIs), such as omeprazole, lansoprazole, rabeprazole, esomeprazole, and pantoprazole, are mainly metabolized by CYP2C19 in the liver. There are genetically determined differences in the activity of this enzyme. The genotypes of CYP2C19 are classified into the three groups, rapid extensive metabolizer (RM), intermediate metabolizer (IM), and poor metabolizer (PM). The pharmacokinetics and pharmacodynamics of PPIs depend on CYP2C19 genotype status. Plasma PPI levels and intragastric pHs during PPI treatment in the RM group are lowest, those in the IM group come next, and those in the PM group are highest of the three groups. These CYP2C19 genotype-dependent differences in pharmacokinetics and pharmacodynamics of PPIs influence the cure rates for the gastro-esophageal reflux disease and H. pylori infection by PPI-based therapies. For the better PPI-based treatment, doses and dosing schemes of PPIs should be optimized based on CYP2C19 genotype status.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Amoxicillin; Aryl Hydrocarbon Hydroxylases; Benzimidazoles; Clarithromycin; Cytochrome P-450 CYP2C19; Drug Interactions; Drug Therapy, Combination; Enzyme Inhibitors; Esomeprazole; Gastroesophageal Reflux; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Mixed Function Oxygenases; Omeprazole; Polymorphism, Genetic; Proton Pump Inhibitors; Rabeprazole

Chirality is one of the main features of biology, and many of the processes essential for life are stereospecific, meaning that one out of two or more isomers may work best in a particular physiological situation. Could this be used in drug development and result in any clinical relevance and true therapeutic advance? There are occasions when the development of one of the isomers might be expected to be advantageous: for example, only one of the isomers may be active, only one of the isomers may cause adverse effects, or one of the isomers may have more advantageous pharmacological properties. As an example of the last, the successful development of esomeprazole will be described. Before the introduction of esomeprazole, the proton pump inhibitor omeprazole was the standard treatment for gastric acid-related diseases, such as gastro-oesophageal reflux disease. A serious type of gastro-oesophageal reflux disease is erosive oesophagitis, an increasingly common condition that may lead to life-threatening complications. Doubling the standard dose of omeprazole from 20 to 40 mg did not improve healing rates (74% versus 75%), and thus a substantial proportion of patients remained unhealed with standard treatment. The (S)-isomer of omeprazole, esomeprazole, was shown to heal more patients than omeprazole as a result of unique metabolic properties that clearly differentiates esomeprazole from omeprazole, the racemate. At comparable doses, these properties lead to several clinical advantages: higher bioavailability in extensive metabolisers (the majority of patients), lower exposure in poor metabolisers, less interindividual variation and a steeper dose-response curve at steady state resulting in a more pronounced inhibition of gastric acid secretion. Esomeprazole has been studied clinically for a variety of acid-related conditions, showing that the compound is as well tolerated and more effective with regard to healing and symptom relief than the recommended treatment with omeprazole. Thus, from this example it is clear that the exploration and development of single-isomer drugs may bring significant advances in treatment options.

Topics: Enzyme Inhibitors; Esomeprazole; Gastroesophageal Reflux; Humans; Omeprazole; Proton Pump Inhibitors; Stereoisomerism; Structure-Activity Relationship

Most new drugs are marketed as single enantiomers but many older agents are still available in racemic form. As these drugs reach the end of their patent life manufacturers become interested in marketing single enantiomer equivalents. This is called 'chiral switching' and it has been claimed that it will bring clinical benefits in terms of improved efficacy, more predictable pharmacokinetics or reduced toxicity. We reviewed the clinical evidence and prices for three recently marketed single enantiomer versions of widely used racemic drugs: escitalopram, esomeprazole and levosalbutamol. Claims of increased efficacy were based on comparisons of non-equivalent doses and any advantages seemed small and clinically unimportant. Prices of esomeprazole and levosalbutamol were higher than their racemic alternatives and we predict that these prices will remain high despite the market presence of generic versions of the racemates. Patent protection and a perception of superiority based on promotion rather than evidence will maintain price premiums for single enantiomer drugs that are not justified on the basis of clinical performance.

Topics: Albuterol; Anti-Asthmatic Agents; Anti-Ulcer Agents; Antidepressive Agents, Second-Generation; Citalopram; Cost-Benefit Analysis; Esomeprazole; Gastroesophageal Reflux; Humans; Stereoisomerism

As the relative efficacy of therapeutic agents in the treatment of gastro-oesophageal reflux disease is related to how consistently and completely gastric acid secretion is suppressed, intragastric pH monitoring is a useful tool in stratifying therapies. If there is no acid in the stomach, there can be none to reflux into the oesophagus. Comparative crossover studies have shown consistently that once-daily esomeprazole (40 mg) provides more effective and longer lasting intragastric acid control than any other proton pump inhibitor currently available in healthy subjects and patients with gastro-oesophageal reflux disease. However, esomeprazole maintained intragastric pH > 4 for > or = 16 h in only about 55% of individuals tested. Thus, if more complete acid suppression is desirable, twice-daily proton pump inhibitor therapy may be advantageous. One such scenario is in patients with Barrett's metaplasia. Data from the ProGERD study suggest that, for each Los Angeles grade of oesophagitis, the healing rate for patients with Barrett's metaplasia is 10-30% less than that for non-Barrett's patients, being as low as 53% in patients with Los Angeles grade D oesophagitis. Also relevant to the Barrett's metaplasia population are studies on the oesophageal mucosa, which show that effective acid suppression favours differentiation and decreases epithelial cell proliferation. Both considerations argue for more intensive gastric acid inhibition than can be achieved with once-daily therapy, leading to experimentation with twice-daily proton pump inhibitor regimens. A randomized, double-blind, three-way crossover study compared esomeprazole 40 mg once daily with esomeprazole 20 mg and 40 mg twice daily and found that both twice-daily regimens were superior, maintaining intragastric pH > 4 for 73%[95% confidence interval (CI), 67-79%] and 80% (95% CI, 75-86%) of the day, respectively, compared with 59% (95% CI, 54-65%) of the day with esomeprazole 40 mg once daily, arguing that a twice-daily regimen may be the preferred strategy for patients with Barrett's metaplasia.

Topics: Anti-Ulcer Agents; Barrett Esophagus; Esomeprazole; Esophagus; Gastric Acid; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Metaplasia; Proton Pump Inhibitors; Randomized Controlled Trials as Topic

Gastroesophageal reflux disease (GERD) is among the most common disorders of the gastrointestinal tract, with symptoms affecting a substantial proportion of the US population on a daily basis. Heartburn and related symptoms arise from a number of pathophysiologic mechanisms, including dilated intercellular spaces, increased duration of acid reflux, greater proximal extent of reflux, and esophageal sensitivity. Chronic reflux may result in serious complications, such as esophageal erosions or ulceration, stricture, and Barrett esophagus. The goals of GERD therapy are to relieve patients' symptoms and prevent complications. Proton pump inhibitors (PPIs) represent the most effective treatment option for GERD, relieving symptoms, healing erosions, and maintaining a healed mucosa. Differences in the pharmacokinetics and pharmacodynamics among the PPIs may result in differences in intragastric pH holding time as well as the onset of symptom relief. Lansoprazole and esomeprazole produce similar degrees and onset of symptom relief, with both providing greater symptom relief as compared with omeprazole. Although manufactured as capsules containing enteric-coated granules, lansoprazole, omeprazole, and esomeprazole maintain their high level of pharmacologic efficacy when the capsule contents are emptied into soft foods or various liquids. Lansoprazole and pantoprazole also are manufactured as intravenous formulations, and lansoprazole is available as strawberry-flavored granules for oral suspension and as an orally disintegrating tablet. These alternative routes of administration are particularly beneficial in the management of acid-related disorders in infants, children, the elderly, and patients of all ages who have difficulty swallowing or are unable to swallow intact capsules or tablets and those in the critical care setting.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Biological Availability; Dose-Response Relationship, Drug; Drug Administration Schedule; Enzyme Inhibitors; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Middle Aged; Omeprazole; Patient Satisfaction; Prognosis; Proton Pump Inhibitors; Risk Assessment; Severity of Illness Index; Treatment Outcome

Control of gastric acid secretion by antisecretory agents has been the cornerstone of therapy in the successful management of all acid-related disorders, including gastro-oesophageal reflux disease (GERD), and duodenal and gastric ulcer. Treatment efficacy has been strongly correlated with degree and duration of acid suppression within the 24-h period and with total duration of therapy. All proton pump inhibitors are highly effective for the healing of ulcers and erosive oesophagitis. All have closely similar mechanisms of action, yet important pharmacological differences exist, which can significantly impact certain aspects of their clinical efficacy. Rabeprazole's rapid activation over a wide pH range may be the explanation for its early onset of effective acid inhibition compared with other proton pump inhibitors such as omeprazole, lansoprazole and pantoprazole. Like rabeprazole, esomeprazole is also a potent inhibitor of gastric acid at steady state, although it is thought that rabeprazole may provide enhanced first-day acid suppression compared with esomeprazole. First-day antisecretory efficacy should produce faster symptom relief, a hypothesis supported by clinical data. Moreover, drugs with pharmacological profiles that include both rapid onset and potent antisecretory effects should help control healthcare costs by reducing the need for otherwise commonly used twice-daily proton pump inhibitor administration.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Esomeprazole; Gastric Acid; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Omeprazole; Proton Pump Inhibitors; Rabeprazole; Wound Healing

Pantoprazole (Protonix) is an irreversible proton pump inhibitor (PPI) that reduces gastric acid secretion. In combination with two antimicrobial agents (most commonly metronidazole, clarithromycin or amoxicillin) for 6-14 days, pantoprazole 40 mg twice daily produced Helicobacter pylori eradication rates of 71-93.8% (intent-to-treat [ITT] or modified ITT analysis) in patients without known antibacterial resistance. Pantoprazole-containing triple therapy was at least as effective as omeprazole- and similar in efficacy to lansoprazole-containing triple therapy in large trials. In the treatment of moderate to severe gastro-oesophageal reflux disease (GORD), oral pantoprazole 40 mg/day was as effective as other PPIs (omeprazole, omeprazole multiple unit pellet system, lansoprazole and esomeprazole) and significantly more effective than histamine H(2)-antagonists. Pantoprazole 20 mg/day provided effective mucosal healing in patients with GORD and mild oesophagitis. Intravenous pantoprazole 40 mg/day can be used in patients who are unable to take oral medication. Oral pantoprazole 20-40 mg/day for up to 24 months prevented relapse in most patients with healed GORD. According to preliminary data, oral pantoprazole 20 or 40 mg/day was effective at healing and preventing non-steroidal anti-inflammatory drug (NSAID)-related ulcers, and intravenous pantoprazole was at least as effective as intravenous ranitidine in preventing ulcer rebleeding after endoscopic haemostasis. Oral or intravenous pantoprazole up to 240 mg/day maintained target acid output levels in most patients with hypersecretory conditions, including Zollinger-Ellison syndrome. Oral and intravenous pantoprazole appear to be well tolerated in patients with acid-related disorders in short- and long-term trials. Tolerability with oral pantoprazole was similar to that with other PPIs or histamine H(2)-antagonists in short-term trials. Formal drug interaction studies have not revealed any clinically significant interactions between pantoprazole and other agents. In conclusion, pantoprazole is an effective agent in the management of acid-related disorders. As a component of triple therapy for H. pylori eradication and as monotherapy for the healing of oesophagitis and maintenance of GORD, pantoprazole has shown similar efficacy to other PPIs and greater efficacy than histamine H(2)-antagonists. Limited data suggest that it is also effective in Zollinger-Ellison syndrome and in preventing ulcer rebleeding.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Benzimidazoles; Clinical Trials as Topic; Dose-Response Relationship, Drug; Esomeprazole; Gastroesophageal Reflux; Helicobacter Infections; Humans; Omeprazole; Pantoprazole; Peptic Ulcer; Sulfoxides; Zollinger-Ellison Syndrome

Esomeprazole (Nexium, AstraZeneca) is the (S)-isomer of omeprazole and the first proton pump inhibitor to be developed as an optical isomer. Esomeprazole has an improved pharmacokinetic profile, resulting in increased systemic exposure and less interindividual variability compared with omeprazole, and more effective suppression of gastric acid production compared with other proton pump inhibitors. In several large, double-blind, randomised trials, significantly higher rates of endoscopically-confirmed healing of erosive oesophagitis and resolution of heartburn have been achieved in patients with gastro-oesophageal reflux disease receiving 8 weeks of esomeprazole 40 mg o.d. compared with those receiving omeprazole 20 mg o.d. or lansoprazole 30 mg o.d. In the maintenance of healed erosive oesophagitis, esomeprazole 10, 20 or 40 mg o.d. was significantly more effective than placebo in two 6-month, randomised, double-blind trials. Additionally, esomeprazole 20 mg o.d. was more effective than lansoprazole 15 mg in the maintenance of healed erosive oesophagitis in another 6-month, randomised, double-blind trial. Healing of oesophagitis was also effectively maintained by esomeprazole 40 mg o.d. in a 12-month non-comparative trial. Esomeprazole 20 or 40 mg o.d. effectively relieved heartburn in patients with gastro-oesophageal reflux disease without oesophagitis in two 4-week, placebo-controlled trials. Clinical trials have shown that triple therapy with esomeprazole 40 mg o.d. in combination with amoxicillin and clarithromycin produced Helicobacter pylori eradication rates similar to those obtained using triple therapy involving twice-daily dosing with other proton pump inhibitors. Esomeprazole is well-tolerated, with a spectrum and incidence of adverse events similar to those associated with omeprazole.

Topics: Anti-Ulcer Agents; Dose-Response Relationship, Drug; Esomeprazole; Esophagitis, Peptic; Gastric Acid; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole; Proton Pump Inhibitors; Randomized Controlled Trials as Topic

To compare the efficacy of esomeprazole, 20 mg once daily, vs. lansoprazole, 15 mg once daily, for the maintenance treatment of patients with healed reflux oesophagitis.. During the initial open healing phase, 1391 patients with endoscopically verified reflux oesophagitis and a history of heartburn, with or without acid regurgitation, received esomeprazole 40 mg for 4-8 weeks. Patients who were healed (identified by endoscopy at 4 or 8 weeks) and symptom free were then randomized to receive 6 months of treatment with esomeprazole, 20 mg once daily, or lansoprazole, 15 mg once daily.. Esomeprazole, 20 mg once daily, maintained a significantly higher proportion of patients in remission than lansoprazole, 15 mg once daily, over 6 months [83% (95% CI, 80-86%) of esomeprazole recipients compared with 74% (95% CI, 70-78%) of lansoprazole recipients; P < 0.0001; life table estimates]. When data were analysed according to baseline Los Angeles grade classification, esomeprazole, 20 mg once daily, achieved consistently higher remission rates across all grades of disease severity, whereas the efficacy of lansoprazole decreased to a greater extent with increasing severity of reflux oesophagitis.. Esomeprazole, 20 mg once daily, is more effective than lansoprazole, 15 mg once daily, in maintaining remission in patients with healed reflux oesophagitis.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Double-Blind Method; Esomeprazole; Esophagitis; Female; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Recurrence; Survival Analysis; Treatment Outcome

Gastric acid suppression is the most effective medical therapy to control acidic gastro-oesophageal reflux: individuals in whom therapy fails usually have inadequate acid suppression. Twenty-four-hour intragastric pH-metry measures the percentage of time that gastric pH is above 4 or 3, the critical thresholds for tissue damage and symptom generation in the distal oesophagus. Effective medical therapy must control gastric acidity throughout the daytime, including the postprandial period. It is therefore useful to report the percentage of patients in whom gastric acidity is controlled above pH 4 for at least 16 out of 24 h. Esomeprazole was compared with standard-dose proton pump inhibitors in healthy volunteers and patients with gastro-oesophageal reflux disease. Esomeprazole, 40 mg daily, was significantly more effective at controlling gastric acidity above pH 4 for more than 16 h than lansoprazole, 30 mg daily (38% of individuals vs. 5%, respectively). Esomeprazole, 40 mg daily, also suppressed gastric acidity more effectively and in more individuals than pantoprazole, 40 mg daily, and rabeprazole, 20 mg daily. Esomeprazole, 20 mg daily, was significantly more effective at controlling gastric acidity than lansoprazole, 15 mg daily. The improved acid control with esomeprazole compared with other proton pump inhibitors is likely to result in superior healing rates and improved symptom relief, with fewer therapy-resistant patients.

Topics: Anti-Ulcer Agents; Esomeprazole; Gastric Acid; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Proton Pump Inhibitors

Plasma concentration measurements have confirmed that the advantageous hepatic metabolism of esomeprazole results in a greater delivery of acid suppressant to the systemic circulation, compared with an equal dose of omeprazole. Also, this superior delivery has been shown to cause a more consistent and greater suppression of pentagastrin-stimulated gastric acid secretion by esomeprazole, 20 mg, compared with omeprazole, 20 mg. The superior acid-suppressant properties of esomeprazole have been revealed by extensive 24-h intragastric pH-monitoring studies. Compared with omeprazole, 20 mg, esomeprazole, 20 mg and 40 mg, has been shown to give superior outcomes on three key measures of antisecretory effect: (1) consistency amongst individuals; (2) duration over the 24-h cycle; (3) overall impact on pH. As there is a substantial increment of acid control from esomeprazole, 20 mg, to esomeprazole, 40 mg, this latter dose is the most appropriate to investigate for modern initial therapy of reflux disease, with the aim of achieving the highest possible response rates in the shortest possible time.

Topics: Anti-Ulcer Agents; Esomeprazole; Gastric Acid; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Omeprazole; Pentagastrin; Proton Pump Inhibitors

Large clinical trials in patients with reflux oesophagitis have shown esomeprazole, 40 mg once daily, to be convincingly superior in the healing of oesophagitis when compared with both omeprazole, 20 mg once daily, and lansoprazole, 30 mg once daily. The greatest advantage for esomeprazole is with healing of the more severe grades of oesophagitis. Esomeprazole, 40 mg once daily, has also been shown to be significantly superior in the treatment of heartburn. Studies in endoscopy-negative patients, or in both oesophagitis and endoscopy-negative patients, have demonstrated good efficacy for esomeprazole, with high levels of symptom control achieved in the first 7 days of therapy.

Topics: Anti-Ulcer Agents; Double-Blind Method; Esomeprazole; Gastroesophageal Reflux; Gastroscopy; Humans; Omeprazole; Randomized Controlled Trials as Topic

Proton pump inhibitors (PPIs) are today used at different recommended doses for treatment of acid-related gastro-esophageal, gastric and gastro-duodenal diseases. We reviewed the literature regarding inhibition of acid secretion and healing rates for the different PPIs. Acid secretion in vitro and in vivo as well as healing and relapse rates were similar on a milligram basis for omeprazole, lansoprazole, rabeprazole, and pantoprazole. Rabeprazole had a somewhat faster onset of inhibition of acid secretion; the clinical value of this however seems limited. Esomeprazole had a somewhat stronger inhibitory effect on acid secretion in vivo compared with other PPIs. Studies demonstrating an important clinical advantage of esomeprazole compared to other PPIs are however lacking.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Dose-Response Relationship, Drug; Enzyme Inhibitors; Esomeprazole; Gastric Acid; Gastroesophageal Reflux; Humans; Lansoprazole; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Sulfoxides

The primary therapeutic endpoint for patients with gastroesophageal reflux disease is complete relief of symptoms and improvement in quality of life. The withdrawal of cisapride has created a vacuum in the prokinetic market, with few promising drugs in the pipeline. Reflux inhibitors are being considered for clinical trials, but as of yet are unavailable. Proton pump inhibitors (PPIs) continue to be the backbone of therapy for acid suppression, providing excellent relief of symptoms and healing of erosive esophagitis. Isomeric technology with esomeprazole as the prototype represents an advance in PPI pharmacology. Antireflux surgery is now more patient-friendly, with shorter hospitalization and less major morbidity compared to open fundoplication, but surgery is at best equal to medical therapy when optimal doses of antisecretory therapy are used. Two endoscopic procedures were recently approved by the U.S. Food and Drug Administration for treatment of gastroesophageal reflux disease: radiofrequency energy delivery to the gastroesophageal junction, and transoral flexible endoscopic suturing. These techniques should be used selectively until we have more data and until results are compared to the safe and highly effective medical therapies.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Endoscopy, Gastrointestinal; Esomeprazole; Esophagitis; Gastroesophageal Reflux; Humans; Lansoprazole; Length of Stay; Proton Pump Inhibitors; Treatment Outcome

The U.S. Food and Drug Administration's Nonprescription Drugs Advisory Committee and Gastroenterological Drugs Advisory Committee recommended approval of omeprazole as an over-the-counter treatment of heartburn in patients who have at least two episodes of heartburn each week. The consumer studies that have been conducted indicate that the majority of patients understand the proposed labeling and could use the proposed label to determine if the omeprazole therapy was appropriate for them. Esomeprazole is an effective agent in the treatment of gastroesophageal reflux disease (GERD) and erosive esophagitis. Newer studies continue to support its efficacy and safety in the treatment of these conditions. Several of the most recent studies have included comparisons with other proton pump inhibitors. The results of these studies indicate that all the proton pump inhibitors are effective in treating GERD and erosive esophagitis and that some patients would benefit from esomeprazole therapy.

Topics: Anti-Ulcer Agents; Clinical Trials as Topic; Drug Labeling; Enzyme Inhibitors; Esomeprazole; Esophagitis; Gastroesophageal Reflux; Humans; Omeprazole; Proton Pump Inhibitors

On-demand therapy is an established modality in long-term therapy with histamine-2-receptor antagonists, in cases of mild non-erosive gastro-oesophageal reflux disease. In the literature, only a few studies have specifically addressed the problem of proton pump inhibitors on-demand treatment. The evidence, so far, available suggests that this might be an effective modality of long-term treatment in the majority of patients with non-erosive gastro-oesophageal reflux disease. This treatment modality appears to be the most cost-effective and the best tolerated medical regimen for gastro-oesophageal reflux disease. It also seems to be able to restore the impairment of health-related quality of life due to gastro-oesophageal reflux disease symptoms. Although the current standard of care for patients with non-erosive gastro-oesophageal reflux disease is maintenance therapy with daily administration of a proton pump inhibitor agent, on-demand therapy, with the same drug, may be a reasonable long-term choice. The ideal proton pump inhibitors for such treatment will be those with a more rapid onset of action, more profound acid inhibition, more predictable therapeutic effect and less drug-drug interactions. Newer proton pump inhibitors, like esomeprazole, the S-chiral isomer of omeprazole, are promising drugs for on-demand treatment of gastro-oesophageal reflux disease.

Topics: Esomeprazole; Gastroesophageal Reflux; Humans; Omeprazole; Proton Pump Inhibitors; Ranitidine

The burden of gastroesophageal reflux disease (GERD) results from its widespread prevalence and the unfavorable impact of its symptoms on well-being and quality of life. Whereas abnormalities of the antireflux barrier (lower esophageal sphincter) are important in the pathophysiology of GERD, pharmacologic therapy for GERD is based on suppression of acid, which is responsible for the majority of the symptoms and for epithelial damage. Proton pump inhibitors (PPIs) are the agents of choice for achieving the goals of medical therapy in GERD, which include symptom relief, improvement in quality of life, and healing and prevention of mucosal injury. As a class, these drugs are extremely safe. The newest PPI, esomeprazole, brings a statistically significant increase in healing of mucosal injury and symptom relief in patients with erosive esophagitis, compared with omeprazole and lansoprazole. This article reviews the role of medical therapy in the short- and long-term management of symptomatic patients with or without erosive esophagitis, including extraesophageal presentations, GERD during pregnancy, and Barrett's esophagus. Management of refractory patients is addressed.

Topics: Barrett Esophagus; Esomeprazole; Esophagitis; Female; Gastroesophageal Reflux; Humans; Omeprazole; Pregnancy; Pregnancy Complications; Proton Pump Inhibitors; Treatment Outcome

Esomeprazole (S-isomer of omeprazole), the first single optical isomer proton pump inhibitor, generally provides better acid control than current racemic proton pump inhibitors and has a favourable pharmacokinetic profile relative to omeprazole. In a large well designed 8-week trial in patients (n >5000) with erosive oesophagitis, esomeprazole recipients achieved significantly higher rates of endoscopically confirmed healed oesophagitis than those receiving lansoprazole. Respective healed oesophagitis rates with once-daily esomeprazole 40mg or lansoprazole 30mg were 92.6 and 88.8%. Overall, esomeprazole was also better than omeprazole, although these differences were not always statistically significance. Ninety-two to 94% of esomeprazole recipients (40mg once daily) achieved healed oesophagitis versus 84 to 90% of omeprazole recipients (20mg once daily). Esomeprazole was effective across all baseline grades of oesophagitis; notably, relative to lansoprazole, as baseline severity of disease increased, the difference in rates of healed oesophagitis also increased in favour of esomeprazole. Resolution of heartburn was also significantly better with esomeprazole 40mg than with these racemic proton pump inhibitors. Long-term (up to 12 months) therapy with esomeprazole effectively maintained healing in these patients. Once-daily esomeprazole 20 or 40mg for 4 weeks resolved symptoms in patients with symptomatic gastro-oesophageal reflux disease (GORD) without oesophagitis. Symptoms were effectively managed in the long-term with symptom-driven on-demand esomeprazole (20 or 40mg once daily). Eradicating Helicobacter pylori infection is considered pivotal to successfully managing duodenal ulcer disease. Seven days' treatment (twice-daily esomeprazole 20mg plus amoxicillin 1g and clarithromycin 500mg) eradicated H. pylori in >/=86% of patients (intention-to-treat), a rate that was similar to equivalent omeprazole-based regimens. Esomeprazole is generally well tolerated, both as monotherapy and in combination with antimicrobial agents, with a tolerability profile similar to that of other proton pump inhibitors. Few patients discontinued therapy because of treatment-emergent adverse events (<3% of patients), with very few (<1%) drug-related serious adverse events reported.. Esomeprazole is an effective, well tolerated treatment for managing GORD and for eradicating H. pylori infection in patients with duodenal ulcer disease. In 8-week double-blind trials, esomeprazole healed oesophagitis and resolved symptoms in patients with endoscopically confirmed erosive oesophagitis and overall, provided better efficacy than omeprazole. Notably, in a large (n >5000 patients) double-blind trial, esomeprazole 40mg provided significantly better efficacy than lansoprazole in terms of healing rates and resolution of symptoms. Long-term therapy with esomeprazole maintained healed oesophagitis in these patients. Esomeprazole also proved beneficial in patients with symptomatic GORD without oesophagitis. Thus, esomeprazole has emerged as an option for first-line therapy in the management of acid-related disorders.

Topics: Databases, Bibliographic; Enzyme Inhibitors; Esomeprazole; Gastroesophageal Reflux; Humans; Omeprazole; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome

Esomeprazole, the S-isomer of omeprazole, is a new proton pump inhibitor. Esomeprazole provides better control of intragastric pH than omeprazole. It is more effective in treating erosive esophagitis in patients with GERD than omeprazole. Esomeprazole can maintain the healing of erosive esophagitis when used daily or on demand. It is also effective for the eradication of Helicobacter pylori infections. The incidence and type of adverse events associated with esomeprazole therapy are infrequent and likely to be similar to omeprazole.

Topics: Anti-Ulcer Agents; Esomeprazole; Esophagitis; Gastroesophageal Reflux; Helicobacter Infections; Humans; Omeprazole; Treatment Outcome

Proton pump inhibitors (PPIs) are now generally considered the drugs of choice for treatment of patients with serious or refractory acid-related diseases. However, despite some popular notions to the contrary, these agents are not equivalent in their pharmacokinetic, pharmacodynamic and efficacy profiles. When the two newest PPIs, rabeprazole and esomeprazole, are compared with the older drugs in this class (omeprazole, lansoprazole and pantoprazole), the newer PPIs offer several key advantages over older agents, particularly in terms of the management of gastro-oesophageal reflux disease. Rabeprazole and esomeprazole achieve more rapid and profound inhibition of acid secretion than do older agents, and they sustain this suppression to provide acid control and symptom relief over 24 h. The balanced hepatic metabolism of rabeprazole, involving both cytochrome P450 (CYP)-mediated reactions in the liver and nonenzymatic reactions, appears to confer an advantage over older PPIs in that genetic polymorphisms for CYP 2C19 do not significantly influence rabeprazole clearance and, potentially, clinical efficacy. The metabolism of esomeprazole also involves CYP 2C19, but the pharmacokinetic effects of genetic differences in the expression of this enzyme are not known. However, esomeprazole is also intended to minimize pharmacological variability. Unlike esomeprazole, the use of rabeprazole is not complicated by clinically significant drug-drug interactions of the type that have been reported for omeprazole and the wide range of medications metabolized by CYP 2C19.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Aryl Hydrocarbon Hydroxylases; Benzimidazoles; Cytochrome P-450 CYP2C19; Cytochrome P-450 Enzyme System; Enzyme Inhibitors; Esomeprazole; Gastric Acid; Gastroesophageal Reflux; Genotype; Humans; Mixed Function Oxygenases; Omeprazole; Proton Pump Inhibitors; Rabeprazole

The recent introduction of proton pump inhibitors has extraordinarily improved the therapeutic approach to gastro-oesophageal reflux disease. The concept of decreasing gastric acid secretion and increasing the pH in the lower oesophagus has been demonstrated to be therapeutically effective and the higher the level of pH achieved, the better the results. In spite of the evident efficacy of these molecules, there are still many patients who will continue to have symptoms despite medical treatment. Proton pump inhibitors suppress gastric acidity, but this effect shows a remarkable interindividual variation depending on different reasons. Thus, it is still possible to optimise medical therapy for gastro-oesophageal reflux disease. Esomeprazole, the S-isomer of omeprazole, has an advantageous metabolism and this particular feature translates into superior clinical efficacy. Clinical trials for initial and long-term treatment across the gastro-oesophageal reflux disease spectrum, have clearly demonstrated the superiority of esomeprazole over omeprazole, even if tolerability and safety are very similar.

Topics: Anti-Ulcer Agents; Biological Availability; Esomeprazole; Esophagitis; Gastric Mucosa; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Isomerism; Omeprazole; Proton Pump Inhibitors; Treatment Outcome

Esomeprazole, a new proton pump inhibitor, is the S-isomer of omeprazole and is the first such inhibitor to be developed as a single isomer. Esomeprazole provided better control of intragastric pH than omeprazole, lansoprazole and pantoprazole in trials conducted in patients with gastro-oesophageal reflux disease (GORD) or healthy volunteers (n = 20 to 115). In 2 large randomised, double-blind multicentre trials esomeprazole 20 and/or 40mg for 8 weeks produced higher healing rates of erosive oesophagitis and better symptom control than omeprazole 20 mg in patients with GORD. Esomeprazole 10, 20 or 40mg once daily for 6 months maintained healing versus placebo (p < 0.001) in patients with endoscopically confirmed healed erosive oesophagitis in 2 large randomised, double-blind multicentre trials. Similarly, symptom-driven on-demand use of esomeprazole effectively controlled symptoms of GORD (heartburn) for 6 months in 2 large placebo-controlled trials. Esomeprazole-based triple therapy for 7 days was as effective for eradication of Helicobacter pylori as longer omeprazole-based therapy in 2 randomised double-blind trials including about 450 patients each. Endoscopically confirmed ulcer healing 4 weeks after treatment initiation was reported in about 90% of patients with active duodenal ulcer in both treatment groups. Esomeprazole-based triple therapy for 10 days was more effective than esomeprazole plus clarithromycin for eradication of H. pylori in 233 patients.

Topics: Animals; Anti-Ulcer Agents; Clinical Trials as Topic; Duodenal Ulcer; Enzyme Inhibitors; Esomeprazole; Gastroesophageal Reflux; Helicobacter pylori; Humans; Omeprazole; Stereoisomerism

Efficacy of proton pump inhibitors is limited in patients with nonerosive reflux disease (NERD). The aim of this study was to comparatively evaluate the efficacy and safety of esomeprazole with sodium bicarbonate and esomeprazole alone.. This was a multicenter, randomized, double-blind, active-controlled, noninferiority comparative study. A total of 379 patients with NERD were randomly allocated to receive either Esoduo. A total of 355 patients completed the study (180 in the Esoduo. Esoduo

Topics: Double-Blind Method; Esomeprazole; Gastroesophageal Reflux; Heartburn; Humans; Proton Pump Inhibitors; Sodium Bicarbonate; Treatment Outcome

Proton-pump inhibitors (PPIs) are cornerstone treatments for gastro-esophageal reflux disease (GERD); however, evidence suggests that most patients exhibit partial response to PPIs, suggesting the need for novel therapies that can provide an improved and sustained increase in gastric pH.. This study aimed to determine the effect of vonoprazan, a novel, orally active small-molecule potassium-competitive acid blocker, versus esomeprazole, a PPI, in preventing heartburn symptoms over a 4-week treatment period in patients with GERD and a partial response to esomeprazole treatment.. This randomized, double-blind, proof-of-concept, phase 2 clinical trial was conducted between 2016 and 2018 at 39 sites across Europe and designed to evaluate the efficacy and safety of vonoprazan 20 mg once daily (q.d.) and 40 mg q.d. versus esomeprazole 40 mg q.d. after 1:1:1 randomization of symptomatic patients with GERD and a partial response to a healing dose of esomeprazole.. No statistically significant difference in efficacy and safety was observed among treatment groups, and vonoprazan was well tolerated. The trial is registered with the National Board of Health (EudraCT: 2015-001154-14) database.

Topics: Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Heartburn; Humans; Middle Aged; Proton Pump Inhibitors; Treatment Outcome

A national survey in the general population showed that gastroesophageal reflux disease (GERD) is highly prevalent in Mexico.. To compare the efficacy and safety of two isomers, dexrabeprazole (10 mg) vs. esomeprazole (20 mg), in the treatment of GERD for four weeks.. Randomized, multicenter, prospective, double-blind phase III clinical trial in two groups that included 230 patients.. A statistically significant decrease in the severity of GERD symptoms (heartburn, regurgitation, epigastric pain and dysphagia), evaluated using a visual analogue scale, was observed with both treatments. Mean score for dexrabeprazole on Carlsson-Dent questionnaire at 28 days was 2.12, and for esomeprazole, 3.02. Both treatments were effective, with no statistically significant difference being recorded (p < 0.05). On SF-36 health questionnaire, both were observed to improve the quality-of-life score, with no significant difference being identified. Both drugs were well tolerated, and the adverse event incidence profile was low.. In the treatment of non-erosive GERD, the use of dexrabeprazole at 10 mg/day is as effective as esomeprazole 20 mg/day, with the advantage that the dose is lower with an appropriate safety profile.. Una encuesta nacional en población abierta mostró que la enfermedad por reflujo gastroesofágico (ERGE) tiene alta prevalencia en México.. Comparar la eficacia y seguridad de dos isómeros, dexrabeprazol (10 mg) versus esomeprazol (20 mg), en el tratamiento de la ERGE durante cuatro semanas.. Ensayo clínico fase III, aleatorizado, multicéntrico, prospectivo, doble ciego, en dos grupos que incluyeron 230 pacientes.. Con ambos tratamientos se observó disminución estadísticamente significativa en la severidad de los síntomas de ERGE (pirosis, regurgitación, dolor epigástrico y disfagia), evaluados mediante una escala visual análoga. La puntuación promedio de dexrabeprazol en el Cuestionario de Carlsson-Dent a los 28 días fue de 2.12 y la de esomeprazol de 3.02. Ambos tratamientos fueron efectivos, sin diferencia estadísticamente significativa (p < 0.05). En el Cuestionario de Salud SF-36 se observó que ambos mejoraron la puntuación en la calidad de vida, sin diferencia significativa. Ambos medicamentos fueron bien tolerados y el perfil de incidencia de eventos adversos fue bajo.. En el tratamiento de ERGE no erosiva, el uso de 10 mg/día de dexrabeprazol es tan efectivo como 20 mg/día de esomeprazol, con la ventaja de que la dosis es menor con un adecuado perfil de seguridad.

Topics: Esomeprazole; Gastroesophageal Reflux; Humans; Prospective Studies; Rabeprazole; Treatment Outcome

Non-cardiac chest pain (NCCP) is defined as recurrent angina pectoris-like pain without evidence of coronary heart disease, and is usually related to esophageal diseases, such as gastroesophageal reflux disease (GERD). Proton pump inhibitors (PPIs) are important for diagnosis and treatment. Many studies have been conducted on the use of PPIs in patients with GERD-related NCCP. In contrast to standard-dose esomeprazole, the efficacy of half-dose esomeprazole twice daily (BD) has not been established. This study compared the efficacies of the two esomeprazole regimens in GERD-related NCCP.. In this prospective, open-label study, 37 participants with GERD-related NCCP were randomized to receive either 20 mg of esomeprazole BD (n=21) (esomeprazole BD group) or 40 mg once daily (n=16) (esomeprazole once daily [OD] group) for 4 weeks. In both groups, the chest pain score, which was calculated based on the frequency and severity, was evaluated before and 2 and 4 weeks after administering the medication.. The chest pain score significantly improved in both groups (p<0.001). The proportion of patients with chest pain score improvement >50% was 7.7% higher in the esomeprazole BD group than in the esomeprazole OD group (95.2% vs. 87.5%), but the difference was not significant.. Esomeprazole BD was as effective as esomeprazole OD in improving GERD-related NCCP. Although statistically insignificant, the percentage of patients with >50% reduction in the chest pain score was higher in the esomeprazole BD group than in the esomeprazole OD group. Large-scale studies will be needed to assess these findings further.

Topics: Adult; Aged; Chest Pain; Dose-Response Relationship, Drug; Drug Administration Schedule; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pilot Projects; Proton Pump Inhibitors; Treatment Outcome; Young Adult

Non-erosive reflux disease (NERD) pathogenesis has not been thoroughly evaluated. Here, we assessed the response of patients with NERD to proton pump inhibitor (PPI) therapy; changes in the microbiome and biologic marker expression in the esophageal mucosa were also evaluated. Patients with NERD (n = 55) received esomeprazole (20 mg) for eight weeks. The treatment response was evaluated at baseline, week four, and week eight. Esophageal mucosal markers and oropharyngeal and esophageal microbiomes were analyzed in patients who underwent upper gastrointestinal endoscopy at screening (n = 18). Complete and partial response rates at week eight were 60.0% and 32.7% for heartburn, and 61.8% and 29.1% for regurgitation, respectively. The expressions of several inflammatory cytokines, including IL-6, IL-8, and NF-κB, were decreased at week eight. Streptococcus, Haemophilus, Prevotella, Veillonella, Neisseria, and Granulicatella were prevalent regardless of the time-point (baseline vs. week eight) and organ (oropharynx vs. esophagus). The overall composition of oropharyngeal and esophageal microbiomes showed significant difference (P = 0.004), which disappeared after PPI therapy. In conclusion, half-dose PPI therapy for eight weeks could effectively control NERD symptoms. The expression of several inflammatory cytokines was reduced in the esophagus, and oropharyngeal and esophageal microbiomes in patients with NERD showed significant difference. However, the microbial compositions in the oropharynx and esophagus were not affected by PPI therapy in this study. Impact of PPI on the microbiome in patients with NERD should be more investigated in future studies.

Topics: Adult; Aged; Biomarkers; Cytokines; Esomeprazole; Esophageal Mucosa; Esophagus; Female; Gastroesophageal Reflux; Gastrointestinal Microbiome; Humans; Inflammation Mediators; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors

Gastroesophageal reflux disease (GERD) is the most frequent chronic gastrointestinal disorder. It is defined as a condition developed when the reflux of gastric contents causes troublesome symptoms (heartburn and regurgitation). This requires adequate treatment since it can lead to long-term complications including esophagus adenocarcinoma. Proton pump inhibitors (PPI) are generally used to treat GERD due to their high-security profile and efficiency on most patients. However, recurrent reflux despite initial treatment is frequent.. A single-patient trial, placebo-controlled, randomized, double-blind, was carried out from September 25th, 2012, to April 26th, 2013. It included one outpatient at the gastroenterology service in a fourth-level hospital, diagnosed with nonerosive reflux disease (NERD). Yet, his symptoms were heartburn and reflux, and his endoscopic results were normal esophageal mucosa, without hiatal hernia, though pathological pH values. A no-obese male without any tobacco or alcohol usage received esomeprazole 40 mg/day and 40 mg/bid for 24 weeks. A standardized gastroesophageal reflux disease questionnaire (GerdQ) was used weekly to evaluate symptom frequency and severity. The consumption of 90% of the capsules was considered as an adequate treatment adherence. D'agostino-Pearson and Wilcoxon test were used to determine normal or nonnormal distribution and compare both treatments, respectively, both with a significant statistical difference of. The patient completed the study with 96% of adherence. The double dosage of esomeprazole did not improve the control of symptoms compared with the standard dosage. Mean symptomatic score was 9.5±0.5 and 10.2±0.6 for each treatment, respectively (. There was no significant improvement in the patient GERD symptoms increasing the dose of oral esomeprazole during the 6 months of study.

Topics: Double-Blind Method; Esomeprazole; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Research Design; Treatment Outcome

Proton pump inhibitors and vonoprazan (a potassium-competitive acid blocker) are recommended as first-line treatments for gastroesophageal reflux disease (GERD). However, few reports have investigated the onset of action of these agents for GERD symptom relief. The present study compared the symptom relief of esomeprazole with that of vonoprazan via monitoring self-reported GERD symptoms after treatment initiation.. This was a prospective, multicenter, randomized, open-label, parallel group, comparative clinical study between esomeprazole (20 mg/day) and vonoprazan (20 mg/day) administered for 4 weeks to patients with GERD symptoms. Patients who had scores ≥ 8 on the Gastroesophageal Reflux Disease Questionnaire (GerdQ) were defined as having GERD and enrolled in this study. Sixty patients were randomly assigned to either the esomeprazole group (n = 30) or the vonoprazan group (n = 30). Treatment response rates in each drug group were evaluated according to the GerdQ. The Frequency Scale for the Symptoms of GERD (FSSG) scores from the 1st day after treatment initiation and the Global Overall Symptom (GOS) scale scores during treatment were also evaluated.. At 4 weeks, the treatment response rates for symptom relief according to the GerdQ were 88.0% in the esomeprazole group and 81.8% in the vonoprazan group. The GOS scales, which reflect the impact of GERD symptoms, were similar for both groups. The FSSG scores decreased from the 1st to the 14th day in both groups.. There were no substantial differences in the symptom relief between the two groups at any time point in this short-term study.

Topics: Adult; Aged; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Japan; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Pyrroles; Remission Induction; Self Report; Sulfonamides; Time Factors; Treatment Outcome

Proton pump inhibitors (PPI) are widely used for the treatment of gastric acid-related disease, but they are not approved for use in children in Japan. To assess the safety, pharmacokinetics, pharmacodynamics, and efficacy (gastrointestinal symptom improvement) of PPI in Japanese pediatric patients with gastric acid-related disease, we conducted an 8 week, open-label, parallel-group, multicenter, phase I/III study of once-daily oral esomeprazole use.. Japanese children, aged 1-14 years with gastric acid-related disease, were stratified by weight and age into five groups (10 patients/group) to receive esomeprazole as granules for suspension (10 mg) or capsules (10 mg or 20 mg) once daily.. Esomeprazole was absorbed and eliminated rapidly in all groups, with a median time to reach maximum plasma concentration of 1.47-1.75 h, an arithmetic mean terminal elimination half-life of 0.80-1.37 h, and a weight-correlated apparent total body clearance of 0.216-0.343 L/h/kg. Area under the plasma concentration-time curve during a dosage interval and maximum plasma drug concentration were generally higher in groups given a higher dose (20 mg) or with a lower age/weight, but also in patients identified as poor metabolizers on cytochrome P450 2C19 genotype. Most patients who had any upper gastrointestinal symptoms at baseline were asymptomatic at the end of the study. Thirty-three patients (66%) reported ≥1 adverse events, including three patients who reported serious adverse events not judged to be causally related to esomeprazole.. Oral esomeprazole, at 10 mg or 20 mg once daily, had a similar safety, efficacy, and pharmacokinetic profile in Japanese pediatric patients to that previously seen in adults and Caucasian children.

Topics: Administration, Oral; Adolescent; Child; Child, Preschool; Cytochrome P-450 CYP2C19; Endoscopy, Digestive System; Esomeprazole; Female; Gastric Acid; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Japan; Male; Proton Pump Inhibitors

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Dexlansoprazole; Dose-Response Relationship, Drug; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Severity of Illness Index; Structure-Activity Relationship; Time Factors; Young Adult

Esomeprazole is commonly administered with food; however, clinical data to support this practice are lacking. We aimed to determine the effect of postprandial ingestion of esomeprazole on reflux symptoms among patients with gastroesophageal reflux disease (GERD).. Consecutive patients with GERD adequately controlled with esomeprazole 40 mg daily, entered a 2-week lead-in period during which esomeprazole was administered 30 min before breakfast. Patients were then randomized to continue preprandial ingestion or to ingest esomeprazole following a standardized meal. Outcomes included GERD frequency and severity indices, GERD-health-related quality of life (GERD-HRQL) questionnaire and Short Form 36 (SF-36).. Thirty-two patients (17 [53.1%] men, aged 53.5 ± 17.2 years) were included, and 16 (50%) switched to postprandial ingestion of esomeprazole. GERD frequency and severity decreased in both groups (Δ9.0 ± 7.2 vs. Δ10.0 ± 8.1, p = 0.29; Δ6.6 ± 6.8 vs. Δ10.2 ± 7.4, p = 0.57 in postprandial group vs. controls, for frequency and severity, respectively). GERD-HRQL improved in both study groups to a similar degree (Δ10.7 ± 10.5 vs. Δ10.0 ± 13.8, p = 0.97). All SF-36 subscores increased in both groups to a similar degree. In a mixed linear model, there were no differences between the study groups in the changes observed in GERD frequency (p = 0.49), severity (p = 0.32), and GERD-HRQL (p = 0.98) during the study period.. Switching to postprandial administration of esomeprazole is not associated with deterioration in reflux symptoms among patients with GERD. Esomeprazole seems to remain efficacious when administered after meals.

Topics: Adult; Aged; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Linear Models; Male; Middle Aged; Postprandial Period; Proton Pump Inhibitors; Quality of Life; Surveys and Questionnaires; Treatment Outcome

Topics: Esomeprazole; Gastroesophageal Reflux; Humans; Laryngopharyngeal Reflux; Proton Pump Inhibitors

YH4808 is a potassium-competitive acid blocker, developed for the treatment of acid-related disorders. Two clinical studies in healthy male subjects were conducted to evaluate the effect of food on the pharmacokinetics of YH4808.. The first study, a randomized, three-treatment, three-period, crossover study, compared pharmacokinetics of YH4808 (300 mg) after a single dose at fed state with a standard or a high-fat meal to those at fasted state. The second study, a randomized, two-treatment, two-period, crossover study, investigated pharmacokinetics at fasted or fed state with a standard meal after twice daily dose of YH4808 (100 mg) for 7 days. Bloods for pharmacokinetic evaluation were sampled up to 48 h post-dose and 24 h post-dose at steady state, respectively. The pharmacokinetic parameters were estimated by non-compartmental method.. After single dosing, the geometric means of maximum plasma concentration increased by 1.2 and 2.1 times in the fed states with a standard meal and a high-fat meal, respectively, of that in fasted state. Corresponding values of area under the plasma concentration-time curve (AUC) from time 0 to the last measurable time point increased by 1.8 and 2.8 times, respectively. After multiple dosing, the geometric mean for 24-h AUC at steady state slightly increased in fed state by 1.1 times of that in fasted state.. As fat content of the food increased, the systemic exposure of YH4808 after single dosing increased. However, systemic exposures at steady state after multiple dosing between fasted and fed states were similar.. ClinicalTrials.gov registry no.: NCT01520012.

Topics: Administration, Oral; Adult; Antacids; Area Under Curve; Biological Availability; Dietary Fats; Dose-Response Relationship, Drug; Esomeprazole; Female; Food-Drug Interactions; Gastric Acid; Gastroesophageal Reflux; Healthy Volunteers; Humans; Male; Potassium

Reflux symptoms are frequently associated with esophageal acid exposure. However, other potential causes unrelated to acid secretion are possible, and the relationship between acid control and symptomatic improvement remains unclear. This study investigated the correlation between individual intragastric pH control and heartburn relief among subjects with frequent heartburn who are likely to self-treat with over-the-counter (OTC) medications. We hypothesized that improved acid control would provide greater symptomatic improvement among individuals representative of an OTC population.. This phase 4, single-center, randomized, double-blind, placebo-controlled study was conducted in subjects without diagnosed gastroesophageal reflux disease or other gastrointestinal conditions who were experiencing frequent heartburn (≥ 3 episodes/week; ≥ 2 nighttime episodes/week over past 30 days) that was responsive to treatment. Subjects entered a 7-day run-in phase, received placebo BID (before breakfast and dinner), and completed symptom diaries. During the treatment phase, subjects received esomeprazole 20 mg BID, esomeprazole 20 mg then placebo, or placebo BID. Subjects underwent 24-h intragastric pH monitoring at baseline and day 14 and completed daily symptom diaries.. In the per-protocol population (n = 39), mean (SD) change from baseline in percentage of time with intragastric pH > 4 was 58.7% (± 26.4%) versus 41.0% (± 30.4%) for those who did and did not achieve 24-h heartburn relief. Significant correlations were observed between change in percentage of time with intragastric pH > 4 and 24-h heartburn relief (OR 1.028; 95% CI 1.001, 1.055; P = 0.0442) and complete resolution (OR 1.034; 95% CI 1.003, 1.065; P = 0.0301).. Individuals with greater improvements in duration of intragastric acid suppression had an increased likelihood of achieving heartburn relief and resolution. These results indicate that individuals not adequately controlling their intragastric pH may require an escalation in dose of their acid-suppressive therapy, assessment with 24-h pH monitoring, or a change in treatment regimen to address non-reflux-related etiologies of their heartburn.. ClinicalTrials.gov identifier: NCT02708355.. Pfizer Consumer Healthcare, Madison, NJ, USA. Plain language summary available for this article.

Topics: Adult; Double-Blind Method; Drug Administration Schedule; Drug Monitoring; Esomeprazole; Female; Gastric Acidity Determination; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Nonprescription Drugs; Proton Pump Inhibitors; Treatment Outcome

No consensus has been established regarding optimal long-term maintenance therapy in symptomatic gastroesophageal reflux disease (GERD). The aim of this study was to compare the efficacies of on-demand and continuous therapy with esomeprazole as maintenance treatments for GERD.. Patients with upper gastrointestinal (GI) endoscopy-proven GERD who received initial proton pump inhibitor (PPI) therapy for 8 weeks were randomized to an on-demand group (esomeprazole 40 mg) or a continuous group (esomeprazole 20 mg). Intensities and frequencies of heartburn and acid regurgitation were assessed using a 6-point Likert scale (0 = no symptoms; 5 = very severe symptoms) and a 6-point frequency scale (0 = none; 5 = symptoms for > 5 days per week) at baseline (start of maintenance treatment) and after 12 weeks of treatment. Alleviation of symptoms was quantified using percentages of patients with a Likert scale or frequency scale of 0 or 1.. Of the 88 patients enrolled, 8 patients were excluded due to follow-up loss in early period of this study, and finally, 39 in the on-demand group and 41 in the continuous group were analyzed. No significant intergroup difference was found between Likert scale or frequency scale of heartburn or regurgitation at baseline. Percentages of symptom alleviations in the on-demand and continuous groups for intensity of heartburn were 56.4%/48.8% at baseline (P = .523) and 82.1%/87.8% at 12 weeks (P = .471), for frequency of heartburn were 61.5%/46.3% at baseline (P = .173) and 76.9%/87.8% at 12 weeks (P = .200), for intensity of regurgitation was 53.8%/43.9% at baseline (P = .374) and 82.1%/87.8% at 12 weeks (P = .471), and for frequency of regurgitation was 61.5%/56.1% at the baseline (P = .621) and 82.1%/82.9% at 12 weeks (P = .918), respectively. Furthermore, no significant intergroup difference was found for convenience of medication or subjective satisfaction.. Intensities and frequencies of heartburn and regurgitation responded well to maintenance treatment in patients in the on-demand and continuous groups. On-demand therapy with esomeprazole 40 mg appears to be sufficient for maintenance treatment in GERD patients.

Topics: Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Endoscopy, Gastrointestinal; Esomeprazole; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Proton Pump Inhibitors; Treatment Outcome

Proton pump inhibitors and laparoscopic anti-reflux surgery (LARS) offer long-term symptom control to patients with gastro-oesophageal reflux disease (GERD).. To evaluate the process of 'normalisation' of the squamous epithelium morphology of the distal oesophagus on these therapies.. In the LOTUS trial, 554 patients with chronic GERD were randomised to receive either esomeprazole (20-40 mg daily) or LARS. After 5 years, 372 patients remained in the study (esomeprazole, 192; LARS, 180). Biopsies were taken at the Z-line and 2 cm above, at baseline, 1, 3 and 5 years. A severity score was calculated based on: papillae elongation, basal cell hyperplasia, intercellular space dilatations and eosinophilic infiltration. The epithelial proliferative activity was assessed by Ki-67 immunohistochemistry.. A gradual improvement in all variables over 5 years was noted in both groups, at both the Z-line and 2 cm above. The severity score decreased from baseline at each subsequent time point in both groups (P < 0.001, all comparisons), attaining a normal level by 5 years. Corresponding decreases in Ki-67 expression were observed (P < 0.001, all comparisons). No significant differences were found between esomeprazole treatment and LARS. Neither baseline severity score nor Ki-67 expression predicted the risk of treatment failure.. Five years of treatment is generally required before squamous epithelial cell morphology and proliferation are 'normalised' in patients with chronic GERD, despite endoscopic and symptomatic disease control. Control of the acid component of the refluxate seems to play the predominant role in restoring tissue morphology.

Topics: Adult; Biopsy; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Laparoscopy; Male; Middle Aged; Mucous Membrane; Proton Pump Inhibitors; Time Factors; Treatment Outcome; Wound Healing

Proton pump inhibitors (PPIs) are the standard therapy for gastroesophageal reflux disease. In adults, PPI treatment is associated with

Topics: Clostridioides difficile; Clostridium Infections; Esomeprazole; Feces; Female; Gastroesophageal Reflux; Humans; Infant; Longitudinal Studies; Male; Microbiota; Prospective Studies; Proton Pump Inhibitors; Statistics, Nonparametric; Time Factors

To compare the one-week clinical effects of single doses of dexlansoprazole and esomeprazole on grades A and B erosive esophagitis.. We enrolled 175 adult patients with gastroesophageal reflux disease (GERD). The patients were randomized in a 1:1 ratio into two sequence groups to define the order in which they received single doses of dexlansoprazole (. Thirteen patients were lost to follow-up, resulting in 81 patients in each group for the per-protocol analysis. The CSRs for both groups were similar at days 1, 3 and 7. In the subgroup analysis, the female patients achieved higher CSRs in the dexlansoprazole group than in the esomeprazole group at day 3 (38.3%. The overall CSR for GERD patients was similar at days 1-7 for both the dexlansoprazole and esomeprazole groups, although a higher incidence of CSR was observed on day 3 in female patients who received a single dose of dexlansoprazole.

Topics: Adult; Dexlansoprazole; Esomeprazole; Esophagitis, Peptic; Feeding Behavior; Female; Gastroesophageal Reflux; Humans; Intention to Treat Analysis; Male; Middle Aged; Pilot Projects; Proton Pump Inhibitors; Sex Factors; Treatment Outcome

We compared the ability of laparoscopic antireflux surgery (LARS) and esomeprazole to control esophageal acid exposure, over a 5-year period, in patients with chronic gastroesophageal reflux disease (GERD). We also studied whether intraesophageal and intragastric pH parameters off and on therapy were associated with long-term outcomes.. We analyzed data from a prospective, randomized, open-label trial comparing the efficacy and safety of LARS vs esomeprazole (20 or 40 mg/d) over 5 years in patients with chronic GERD. Ambulatory intraesophageal and intragastric 24-hour pH monitoring data were compared between groups before LARS or the start of esomeprazole treatment, and 6 months and 5 years afterward. A secondary aim was to evaluate the association between baseline and 6-month pH parameters and esomeprazole dose escalation, reappearance of GERD symptoms, and treatment failure over 5 years in patients receiving LARS or esomeprazole.. In the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P < .001 vs baseline). In the esomeprazole group (n = 151), the median 24-hour esophageal acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P < .001, therapy vs baseline, and LARS vs esomeprazole). Gastric acidity was stable in both groups. Patients who required a dose increase to 40 mg/d had more severe supine reflux at baseline, and decreased esophageal acid exposure (P < .02) and gastric acidity after dose escalation. Esophageal and intragastric pH parameters, off and on therapy, did not predict long-term symptom breakthrough.. In a prospective study of patients with chronic GERD, esophageal acid reflux was reduced greatly by LARS or esomeprazole therapy. However, patients receiving LARS had significantly greater reductions in 24-hour esophageal acid exposure after 6 months and 5 years. Esophageal and gastric pH, off and on therapy, did not predict long-term outcomes of patients. Abnormal supine acid exposure predicted esomeprazole dose escalation. ClinicalTrials.Gov identifier: NCT00251927 (available: http://clinicaltrials.gov/ct2/show/NCT00251927).

Topics: Adolescent; Adult; Aged; Esomeprazole; Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Treatment Outcome; Young Adult

Sleep disturbances related to reflux symptoms have a significant impact on the daily lives of affected individuals. These analyses identified clinical factors related to resolution of reflux-related sleep disturbance in subjects treated with esomeprazole 20 mg for 14 days.. Data from the first 14 days of 2 similar randomized, double-blind studies were pooled for subjects experiencing frequent heartburn and related sleep disturbances receiving esomeprazole 20 mg (n = 357) or placebo (n = 346). A stepwise logistic regression analysis was performed with pooled and individual study data to evaluate relationships between clinical factors [treatment (esomeprazole vs. placebo), run-in sleep disturbance frequency, occurrence (yes/no) of 24-h, daytime, and nighttime heartburn (yes: ≥1 episode in 14-day treatment period)] and complete sleep disturbance resolution (no disturbances for 7 consecutive days).. Absence of daytime (p = 0.0018) or nighttime (p < 0.0001) heartburn during treatment was a significant predictor of complete sleep disturbance resolution at 14 days for the total population, while higher run-in sleep disturbance frequency (p < 0.0001) was associated with a lower likelihood of resolution. Esomeprazole treatment was an independent significant predictor of improvement across all endpoints (p < 0.0001). A significant treatment by run-in sleep disturbance interaction was observed for complete resolution (p = 0.0231), indicating greater therapeutic benefit with esomeprazole in subgroups with higher run-in symptom frequency.. Lower run-in sleep disturbance frequency, no occurrence of daytime or nighttime heartburn during therapy, and esomeprazole treatment predicted complete reflux-related sleep disturbance resolution. The magnitude of therapeutic benefit for esomeprazole 20 mg over placebo increased with increasing baseline sleep disturbance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Double-Blind Method; Endpoint Determination; Esomeprazole; Female; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Prognosis; Proton Pump Inhibitors; Sleep Wake Disorders; Treatment Outcome; Young Adult

Most patients with gastroesophageal reflux disease experience symptomatic relapse after stopping acid-suppressive medication. The aim of this study was to compare willingness to continue treatment with esomeprazole on-demand versus continuous maintenance therapy for symptom control in patients with non-erosive reflux disease (NERD) after 6 months.. This multicenter, open-label, randomized, parallel-group study enrolled adults with NERD who were heartburn-free after 4 weeks' treatment with esomeprazole 20 mg daily. Patients received esomeprazole 20 mg daily continuously or on-demand for 6 months. The primary variable was discontinuation due to unsatisfactory treatment. On-demand treatment was considered non-inferior if the upper limit of the one-sided 95 % confidence interval (CI) for the difference between treatments was <10 %.. Of 877 patients enrolled, 598 were randomized to maintenance treatment (continuous: n = 297; on-demand: n = 301). Discontinuation due to unsatisfactory treatment was 6.3 % for on-demand and 9.8 % for continuous treatment (difference -3.5 % [90 % CI: -7.1 %, 0.2 %]). In total, 82.1 and 86.2 % of patients taking on-demand and continuous therapy, respectively, were satisfied with the treatment of heartburn and regurgitation symptoms, a secondary variable (P = NS). Mean study drug consumption was 0.41 and 0.91 tablets/day, respectively. Overall, 5 % of the on-demand group developed reflux esophagitis versus none in the continuous group (P < 0.0001). The Gastrointestinal Symptom Rating Scale Reflux dimension was also improved for continuous versus on-demand treatment. Esomeprazole was well tolerated.. In terms of willingness to continue treatment, on-demand treatment with esomeprazole 20 mg was non-inferior to continuous maintenance treatment and reduced medication usage in patients with NERD who had achieved symptom control with initial esomeprazole treatment.. ClinicalTrials.gov identifier (NCT number): NCT02670642 ; Date of registration: December 2015.

Topics: Adult; Drug Administration Schedule; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Heartburn; Humans; Maintenance Chemotherapy; Male; Middle Aged; Patient Satisfaction; Proton Pump Inhibitors; Treatment Outcome

Studies on the therapeutic efficacy of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD) have been recently published. In most of these studies, comparison of only two PPIs have been made. There are few studies on the comparison of four or more PPIs. We aimed to compare the acid inhibitory effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on days 1 and 5 of treatment in patients with GERD, who were extensive metabolizers in regard to the CYP2C19 genotype.. Helicobacter pylori-negative with typical symptoms of GERD patients were randomly divided into four treatment groups. Efficacy analysis on days 1 and 5 were performed on the four groups which comprised 10 (esomeprazole), 11 (rabeprazole), 10 (lansoprazole), and 10 (pantoprazole) patients.. On day 1 of PPI treatment, the mean percentage of time with intragastric Ph>4 were 54%, 58%, 60%, and 35% for the groups, respectively, and on day 5, these values were 67%, 60%, 68%, and 59%, respectively. Esomeprazole, rabeprazole, and lansoprazole were found to be superior to pantoprazole on the first day of treatment.. Pantoprazole is a less potent proton pump inhibitor than the other PPIs tested on the first day of treatment. When the time needed to raise the intragatric pH to over 4 was evaluated, esomeprazole was found to have the most rapid action, followed by lansoprazole and rabeprazole.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Cross-Over Studies; Cytochrome P-450 CYP2C19; Double-Blind Method; Esomeprazole; Female; Gastric Acid; Gastroesophageal Reflux; Genotype; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Middle Aged; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Treatment Outcome

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Biomarkers; Breath Tests; Carbon Radioisotopes; Cytochrome P-450 CYP2C19; Esomeprazole; Female; Gastroesophageal Reflux; Genetic Association Studies; Humans; Male; Middle Aged; Omeprazole; Pantoprazole; Pharmacogenetics; Precision Medicine; Proton Pump Inhibitors; Young Adult

To assess the long-term effect on symptoms and quality of life of esomeprazole 20 mg once daily, a recommended dose for maintenance therapy of gastroesophageal reflux disease (GERD).. This is a post hoc analysis of 5 year data from patients in the LOTUS trial (ClinicalTrials.gov identifier: NCT00251927) who were randomized to esomeprazole 20 mg once daily. All participants had chronic, symptomatic GERD responsive to treatment. Gastrointestinal symptoms were assessed by physicians and by using patient-reported outcome instruments. Investigations included gastrointestinal endoscopy (with biopsy sampling), 24 hour esophageal pH monitoring and laboratory measurements.. In total, 157 of 256 patients randomized to esomeprazole 20 mg once daily remained on this dose until the end of follow-up or study discontinuation, whereas 99 patients had their dose increased because of inadequate symptom control (of these, 29 subsequently returned to the allocated dose). On logistic regression, a long objectively defined GERD history, smoking, female sex, absence of Helicobacter pylori infection and high supine baseline acid reflux into the esophagus were associated with an increased likelihood of requiring dose escalation to esomeprazole 40 mg daily (all p < 0.05). Symptoms were fairly stable and quality of life was normal throughout follow-up in patients remaining on esomeprazole 20 mg once daily, with no more than mild symptom severity, and mean (standard deviation) percentage time with intraesophageal pH <4 was reduced from 10.7 (10.7) pre-randomization to 6.3 (10.2) at 6 months and 4.9 (7.3) at 5 years. The number of serious adverse events was low (0.079 per patient per year).. Post hoc analysis with no control group.. Esomeprazole at a maintenance dose of 20 mg once daily offers effective long-term treatment for chronic GERD in patients initially responsive to the medication, with durable symptom control and sustained reductions in intraesophageal acid exposure.

Topics: Adult; Aged; Endoscopy, Gastrointestinal; Esomeprazole; Esophageal pH Monitoring; Female; Follow-Up Studies; Gastroesophageal Reflux; Health Status; Humans; Male; Middle Aged; Quality of Life; Time Factors; Treatment Outcome

To investigate the resolution of heartburn and gastroesophageal reflux disease (GERD)-related sleep disturbances during the first 14 days of treatment with esomeprazole 20 mg compared to placebo in subjects with frequent nighttime heartburn and GERD-related sleep disturbances.. This was a post hoc analysis of 2 week data from two previously published, similarly designed randomized, placebo-controlled trials of 4 weeks' duration comparing esomeprazole 20 mg, 40 mg (one study), and placebo. Inclusion and exclusion criteria for both trials were the same.. NCT00628342; NCT00660660.. The main outcome measures for this analysis were the resolution and/or relief of GERD-related sleep disturbances during 2 weeks of treatment with esomeprazole 20 mg or placebo. Resolution and/or relief of heartburn symptoms were also measured.. In trial 1, 455 subjects were randomized, with 225 and 229 receiving esomeprazole 20 mg and placebo, respectively. In trial 2, 276 subjects were randomized, with 142 and 132 receiving esomeprazole and placebo, respectively. After 2 weeks, significantly more subjects who received esomeprazole 20 mg (50.5% [95% confidence interval: 43.8%-57.1%] and 39.4% [31.2%-47.6%] in trials 1 and 2, respectively) had resolution of sleep disturbances compared to placebo (19.9% [14.6%-25.2%] and 16.0% [9.6%-22.4%], respectively; p < 0.0001 for both trials). The median time to resolution of sleep disturbances with esomeprazole 20 mg was 1 day in both trials. After 2 weeks, significantly more subjects receiving esomeprazole 20 mg (32.3% [26.1%-38.5%] and 26.3% [18.9%-33.6%] in trials 1 and 2, respectively) had resolution of nighttime heartburn symptoms compared to placebo (5.4% [2.4%-8.4%] and 4.8% [1.1%-8.5%], respectively; p < 0.0001 for both trials).. Esomeprazole 20 mg significantly and effectively reduced nighttime heartburn and GERD-related sleep disturbances in the first 2 weeks of treatment compared to placebo, with rapid resolution of sleep disturbances in the first days of treatment.

Topics: Adult; Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Proton Pump Inhibitors; Sleep Wake Disorders; Treatment Outcome

Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Although treatment with proton pump inhibitors (PPIs) helps to improve GERD symptoms and subjective sleep parameters, the effects of PPI therapy on objective sleep parameters are conflicting. The aim of this study was to examine the effects of esomeprazole treatment on GERD symptoms and sleep parameters assessed using actigraphs and questionnaires.. Thirteen patients with GERD received 20 mg of esomeprazole once daily for two weeks. The patients wore actigraphs from three days before the initiation of PPI treatment to the end of therapy. They were also asked to answer the following self-reported questionnaires: Frequency Scale for the Symptoms of GERD (FSSG), Pittsburg Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Objective sleep parameters were evaluated using actigraphy.. Treatment with esomeprazole significantly decreased the total FSSG score, including the scores for reflux and dysmotility, as well as the ESS score, although it had no effect on the PSQI score. After the second week of treatment, esomeprazole significantly decreased the wake time (from 47.5±39.6 min to 36.0±27.1 min) and sleep latency period (from 19.5±19.8 min to 9.9±10.2 min) and increased the percentage of sleep time (from 89.1±8.8% to 91.9±6.3%); however, improvements were not noted in all objective parameters.. Esomeprazole treatment significantly improves various objective sleep parameters in Japanese patients with GERD. Further placebo-controlled randomized trials are needed to obtain detailed results.

Topics: Actigraphy; Adult; Aged; Asian People; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Sleep; Sleep Wake Disorders; Surveys and Questionnaires; Treatment Outcome

Helicobacter pylori (H. pylori) frequently colonizes the stomach. Gastroesophageal reflux disease (GERD) is a common and costly disease. But the relationship of H. pylori and GERD is still unclear. This study aimed to explore the effect of H. pylori and its eradication on reflux esophagitis therapy.. Patients diagnosed with reflux esophagitis by endoscopy were enrolled; based on rapid urease test and Warth-Starry stain, they were divided into H. pylori positive and negative groups. H. pylori positive patients were randomly given H. pylori eradication treatment for 10 days, then esomeprazole 20 mg bid for 46 days. The other patients received esomeprazole 20 mg bid therapy for 8 weeks. After treatment, three patient groups were obtained: H. pylori positive eradicated, H. pylori positive uneradicated, and H. pylori negative. Before and after therapy, reflux symptoms were scored and compared. Healing rates were compared among groups. The χ2 test and t-test were used, respectively, for enumeration and measurement data.. There were 176 H. pylori positive (with 92 eradication cases) and 180 negative cases. Healing rates in the H. pylori positive eradicated and H. pylori positive uneradicated groups reached 80.4% and 79.8% (P = 0.911), with reflux symptom scores of 0.22 and 0.14 (P = 0.588). Healing rates of esophagitis in the H. pylori positive uneradicated and H. pylori negative groups were, respectively, 79.8% and 82.2% (P = 0.848); reflux symptom scores were 0.14 and 0.21 (P = 0.546).. Based on esomeprazole therapy, H. pylori infection and eradication have no significant effect on reflux esophagitis therapy.

Topics: Adolescent; Adult; Aged; Amoxicillin; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Tinidazole; Young Adult

When administered at a standard dose, proton pump inhibitors (PPIs) do not always provide sufficient acid inhibition for all subjects, particularly in extensive metabolizers (EMs) of CYP2C19. Whether esomeprazole at a dose of 20 mg four times daily dosing (q.i.d.) can attain sufficient acid inhibition throughout 24 h in EMs remains unclear. We therefore investigated the efficacy of esomeprazole q.i.d. for acid inhibition.. In a randomized cross-over design, 30 Helicobacter pylori-negative healthy young Japanese volunteers received esomeprazole at a dose of 20 mg two times a day (b.i.d.) or q.i.d. for 7 days. A pH monitoring was conducted before the trial as a control and on day 7 of both regimens.. Median pH values in the q.i.d. regimen were significantly higher than those with the b.i.d. regimen in EMs (b.i.d.: 5.3, q.i.d.: 6.6, p = 0.022), intermediate metabolizer (IM) (b.i.d.: 5.5, q.i.d.: 6.8, p = 0.005) and poor metabolizer (PM) (b.i.d.: 6.2, q.i.d.: 7.0, p = 0.047), respectively. Median pH with the b.i.d. regimen differed significantly by CYP2C19 genotypes (p = 0.004), but not the q.i.d. regimen (p = 0.384).. Esomeprazole q.i.d. achieved potent acid inhibition in all Helicobacter pylori-negative subjects, irrespective of CYP2C19 genotype, which might be one of the rescue regimens for patients' refractory to PPI treatment.

Topics: Adult; Cross-Over Studies; Cytochrome P-450 CYP2C19; Drug Administration Schedule; Esomeprazole; Female; Gastric Acid; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Japan; Male; Proton Pump Inhibitors; Young Adult

To compare symptom control with esomeprazole regimens for non-erosive reflux disease and chronic gastritis in patients with a negative endoscopy.. This randomized, open-label study was designed in line with clinical practice in China. Patients with typical reflux symptoms for ≥ 3 mo and a negative endoscopy who had a Gastroesophageal Reflux Disease Questionnaire score ≥ 8 were randomized to initial treatment with esomeprazole 20 mg once daily either for 8 wk or for 2 wk. Patients with symptom relief could enter another 24 wk of maintenance/on-demand treatment, where further courses of esomeprazole 20 mg once daily were given if symptoms recurred. The primary endpoint was the symptom control rate at week 24 of the maintenance/on-demand treatment period. Secondary endpoints were symptom relief rate, success rate (defined as patients who had symptom relief after initial treatment and after 24 wk of maintenance treatment), time-to-first-relapse and satisfaction rate.. Based on the data collected in the modified intention-to-treat population (MITT; patients in the ITT population with symptom relief after initial esomeprazole treatment, n = 262), the symptom control rate showed a small but statistically significant difference in favor of the 8-wk regimen (94.9% vs 87.3%, P = 0.0473). Among the secondary endpoints, based on the data collected in the ITT population (n = 305), the 8-wk group presented marginally better results in symptom relief after initial esomeprazole treatment (88.3% vs 83.4%, P = 0.2513) and success rate over the whole study (83.8% vs 72.8%, P = 0.0258). The 8-wk regimen was found to provide a 46% reduction in risk of relapse vs the 2-wk regimen (HR = 0.543; 95%CI: 0.388-0.761). In addition, fewer unscheduled visits and higher patient satisfaction supported the therapeutic benefits of the 8-wk regimen over the 2-wk regimen. Safety was comparable between the two groups, with both regimens being well tolerated.. Chinese patients diagnosed with chronic gastritis achieved marginally better control of reflux symptoms with an 8-wk vs a 2-wk esomeprazole regimen, with a similar safety profile.

Topics: Adult; Asian People; China; Chronic Disease; Drug Administration Schedule; Endoscopy, Gastrointestinal; Esomeprazole; Female; Gastritis; Gastroesophageal Reflux; Humans; Male; Middle Aged; Patient Satisfaction; Proton Pump Inhibitors; Remission Induction; Surveys and Questionnaires; Time Factors; Treatment Outcome

To evaluate safety, tolerability, and symptom improvement with once-daily esomeprazole in children with endoscopically proven gastroesophageal reflux disease (GERD).. In this 8-week, multicenter, randomized, uncontrolled, double-blind study, children ages 1 to 11 years were stratified by weight to receive esomeprazole 5 or 10 mg (children < 20 kg) or 10 or 20 mg (children ≥ 20 kg) once daily. Safety and tolerability was assessed by evaluating adverse events (AEs; both treatment- and non-treatment-related AEs) and changes from baseline in medical history, physical examinations, and clinical laboratory tests. Investigators scored symptom severity every 2 weeks using the Physician's Global Assessment (PGA). Patients' parents rated GERD symptoms of heartburn, acid regurgitation, and epigastric pain (none to severe, 0-3) at baseline (based on past 72 hours) and daily (from past 24 hours).. Of 109 patients randomized, 108 had safety data. AEs were experienced by 68.0% and 65.2% of children < 20 kg receiving esomeprazole 5 and 10 mg, respectively, and 83.9% and 82.8% of children ≥ 20 kg receiving esomeprazole 10 and 20 mg, respectively, regardless of causality. Overall, only 9.3% of patients reported 13 treatment-related AEs; the most common were diarrhea (2.8% [3/108]), headache (1.9% [2/108]), and somnolence (1.9% [2/108]). Vomiting, a serious AE in 2 patients, was not judged by the investigator to be related to treatment. At the final visit, PGA scores improved significantly from baseline (P < 0.001). Of 58 patients with moderate to severe baseline PGA symptom scores, 91.4% had lower scores by the final visit. GERD symptom scores were significantly improved from baseline to the final week of the study in all of the treatment groups (P < 0.01) CONCLUSIONS: In children ages 1 to 11 years with endoscopically proven GERD, esomeprazole (at daily doses of 5, 10, or 20 mg) was generally well tolerated. The frequency and severity of GERD-related symptoms were significantly reduced during the active treatment period.

Topics: Child; Child, Preschool; Double-Blind Method; Esomeprazole; Gastroesophageal Reflux; Humans; Infant; Proton Pump Inhibitors

Acid suppression with a proton pump inhibitor is standard treatment for gastroesophageal reflux disease and erosive esophagitis in adults and increasingly is becoming first-line therapy for children aged 1-17 years. We evaluated endoscopic healing of erosive esophagitis with esomeprazole in young children with gastroesophageal reflux disease and described esophageal histology.. Children aged 1-11 years with endoscopically or histologically confirmed gastroesophageal reflux disease were randomized to esomeprazole 5 or 10 mg daily (< 20 kg) or 10 or 20 mg daily (≥ 20 kg) for 8 weeks. Patients with erosive esophagitis underwent an endoscopy after 8 weeks to assess healing of erosions.. Of 109 patients, 49% had erosive esophagitis and 51% had histologic evidence of reflux esophagitis without erosive esophagitis. Of the 45 patients who had erosive esophagitis and underwent follow-up endoscopy, 89% experienced erosion resolution. Dilation of intercellular space was reported in 24% of patients with histologic examination.. Esomeprazole (0.2-1.0 mg/kg) effectively heals macroscopic and microscopic erosive esophagitis in this pediatric population with gastroesophageal reflux disease. Dilation of intercellular space may be an important histologic marker of erosive esophagitis in children.

Topics: Child; Child, Preschool; Double-Blind Method; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Infant; Male; Proton Pump Inhibitors; Treatment Outcome; Wound Healing

To evaluate the pharmacokinetics and acid-suppressive effects of esomeprazole in infants with gastroesophageal reflux disease (GERD).. In this single-blind, randomized, parallel-group study, 50 infants 1 to 24 months old with symptoms of GERD, and ≥ 5% of time with intraesophageal pH <4 during 24-hour dual pH monitoring, received oral esomeprazole 0.25 mg/kg (n = 26) or 1 mg/kg (n = 24) once daily for 1 week. Intraesophageal and intragastric pH were recorded at 1 week, and blood samples were taken for pharmacokinetic analysis.. At baseline, mean percentages of time with intragastric pH > 4 and intraesophageal pH < 4 were 30.5% and 11.6%, respectively, in the esomeprazole 0.25 mg/kg group and 28.6% and 12.5% in the esomeprazole 1 mg/kg group. After 1 week of treatment, times with intragastric pH >4 were 47.9% and 69.3% in the esomeprazole 0.25 mg/kg and 1 mg/kg groups, respectively (P < 0.001 vs baseline), and times with intraesophageal pH < 4 were 8.4% (P < 0.05 vs baseline) and 5.5% (P < 0.001 vs. baseline), respectively. The mean number of acid reflux episodes of > 5 minutes duration decreased from 6 at baseline to 3 and 2 with esomeprazole 0.25 mg/kg and 1 mg/kg, respectively. The geometric mean AUC0-t of esomeprazole were 0.24 and 1.79 μmol · h/L for the 0.25 mg/kg and 1 mg/kg dosages of esomeprazole, respectively. Both esomeprazole dosages were well tolerated.. Oral treatment with esomeprazole 0.25 mg/kg and 1 mg/kg was well tolerated and provided dose-related acid suppression, dose-related exposure to esomeprazole, and decreased esophageal acid exposure in infants 1-24 months old with GERD.

Topics: Administration, Oral; Child, Preschool; Esomeprazole; Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Male; Proton Pump Inhibitors; Single-Blind Method; Treatment Outcome

The aim of the study was to evaluate erosive esophagitis healing and symptom improvement with once-daily esomeprazole in children ages 12 to 36 months with endoscopically or histologically proven gastroesophageal reflux disease (GERD).. Data from children ages 12 to 36 months were included in a post-hoc analysis of an 8-week, multicenter, randomized, and double-blind by dose strata study of patients ages 1 to 11 years with endoscopically or histologically confirmed GERD. Children were randomized to receive esomeprazole 5 or 10 mg once daily. Patients underwent endoscopy and, if required, mucosal biopsy at baseline. Patients who had erosive esophagitis (graded using the Los Angeles classification system) at baseline underwent a follow-up endoscopy at final study visit to assess healing of erosive esophagitis. Investigators scored severity of GERD symptoms at baseline and every 2 weeks using the Physician Global Assessment.. Thirty-one of 109 primary study patients ages 12 to 36 months were included in the post hoc analysis. At baseline, 15 patients (48.4%) had erosive esophagitis, underwent follow-up endoscopy, and were healed after 8 weeks of esomeprazole treatment. Of the 19 patients with moderate-to-severe baseline Physician Global Assessment symptom scores, 84.2% had lower scores by the final visit. Following esomeprazole treatment, GERD symptoms were significantly improved from baseline to final visit (P ≤ 0.0018).. Esomeprazole 5 or 10 mg may be used to successfully treat erosive esophagitis and symptoms of GERD in children as young as 1 year. Moreover, although not yet validated in pediatric patients, the Los Angeles classification system was useful in grading erosive esophagitis in children ages 12 to 36 months.

Topics: Child, Preschool; Double-Blind Method; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Infant; Male; Proton Pump Inhibitors; Treatment Outcome; Wound Healing

Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/ or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD.. In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5-10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5-10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded.. Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated.. The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy.

Topics: Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Infant; Male; Proton Pump Inhibitors

To evaluate safety, tolerability, and symptom improvement with once-daily esomeprazole in children with endoscopically proven gastroesophageal reflux disease (GERD).. In this 8-week, multicenter, randomized, uncontrolled, double-blind study, children ages 1 to 11 years were stratified by weight to receive esomeprazole 5 or 10 mg (children < 20 kg) or 10 or 20 mg (children ≥ 20 kg) once daily. Safety and tolerability was assessed by evaluating adverse events (AEs; both treatment- and non-treatment-related AEs) and changes from baseline in medical history, physical examinations, and clinical laboratory tests. Investigators scored symptom severity every 2 weeks using the Physician's Global Assessment (PGA). Patients' parents rated GERD symptoms of heartburn, acid regurgitation, and epigastric pain (none to severe, 0-3) at baseline (based on past 72 hours) and daily (from past 24 hours).. Of 109 patients randomized, 108 had safety data. AEs were experienced by 68.0% and 65.2% of children <20 kg receiving esomeprazole 5 and 10 mg, respectively, and 83.9% and 82.8% of children ≥ 20 kg receiving esomeprazole 10 and 20 mg, respectively, regardless of causality. Overall, only 9.3% of patients reported 13 treatment-related AEs; the most common were diarrhea (2.8% [3/108]), headache (1.9% [2/108]), and somnolence (1.9% [2/108]). Vomiting, a serious AE in 2 patients, was not judged by the investigator to be related to treatment. At the final visit, PGA scores improved significantly from baseline (P < 0.001). Of 58 patients with moderate to severe baseline PGA symptom scores, 91.4% had lower scores by the final visit. GERD symptom scores were significantly improved from baseline to the final week of the study in all of the treatment groups (P < 0.01) CONCLUSIONS:: In children ages 1 to 11 years with endoscopically proven GERD, esomeprazole (at daily doses of 5, 10, or 20 mg) was generally well tolerated. The frequency and severity of GERD-related symptoms were significantly reduced during the active treatment period.

Topics: Child; Child, Preschool; Diarrhea; Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Headache; Humans; Infant; Male; Pediatrics; Proton Pump Inhibitors; Treatment Outcome

To evaluate the pharmacokinetics and acid-suppressive effects of esomeprazole in infants with gastroesophageal reflux disease (GERD).. In this single-blind, randomized, parallel-group study, 50 infants 1 to 24 months old with symptoms of GERD, and ≥ 5% of time with intraesophageal pH <4 during 24-hour dual pH monitoring, received oral esomeprazole 0.25 mg/kg (n = 26) or 1 mg/kg (n = 24) once daily for 1 week. Intraesophageal and intragastric pH were recorded at 1 week, and blood samples were taken for pharmacokinetic analysis.. At baseline, mean percentages of time with intragastric pH >4 and intraesophageal pH <4 were 30.5% and 11.6%, respectively, in the esomeprazole 0.25 mg/kg group and 28.6% and 12.5% in the esomeprazole 1 mg/kg group. After 1 week of treatment, times with intragastric pH >4 were 47.9% and 69.3% in the esomeprazole 0.25 mg/kg and 1 mg/kg groups, respectively (P < 0.001 vs baseline), and times with intraesophageal pH <4 were 8.4% (P < 0.05 vs baseline) and 5.5% (P < 0.001 vs. baseline), respectively. The mean number of acid reflux episodes of >5 minutes duration decreased from 6 at baseline to 3 and 2 with esomeprazole 0.25 mg/kg and 1 mg/kg, respectively. The geometric mean AUC0-t of esomeprazole were 0.24 and 1.79 μmol · h/L for the 0.25 mg/kg and 1 mg/kg dosages of esomeprazole, respectively. Both esomeprazole dosages were well tolerated.. Oral treatment with esomeprazole 0.25 mg/kg and 1 mg/kg was well tolerated and provided dose-related acid suppression, dose-related exposure to esomeprazole, and decreased esophageal acid exposure in infants 1-24 months old with GERD.

Topics: Administration, Oral; Child, Preschool; Esomeprazole; Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Male; Pediatrics; Proton Pump Inhibitors; Single-Blind Method; Treatment Outcome

Acid suppression with a proton pump inhibitor is standard treatment for gastroesophageal reflux disease and erosive esophagitis in adults and increasingly is becoming first-line therapy for children aged 1-17 years. We evaluated endoscopic healing of erosive esophagitis with esomeprazole in young children with gastroesophageal reflux disease and described esophageal histology.. Children aged 1-11 years with endoscopically or histologically confirmed gastroesophageal reflux disease were randomized to esomeprazole 5 or 10 mg daily (<20 kg) or 10 or 20 mg daily (≥ 20 kg) for 8 weeks. Patients with erosive esophagitis underwent an endoscopy after 8 weeks to assess healing of erosions.. Of 109 patients, 49% had erosive esophagitis and 51% had histologic evidence of reflux esophagitis without erosive esophagitis. Of the 45 patients who had erosive esophagitis and underwent follow-up endoscopy, 89% experienced erosion resolution. Dilation of intercellular space was reported in 24% of patients with histologic examination.. Esomeprazole (0.2-1.0 mg/kg) effectively heals macroscopic and microscopic erosive esophagitis in this pediatric population with gastroesophageal reflux disease. Dilation of intercellular space may be an important histologic marker of erosive esophagitis in children.

Topics: Anti-Ulcer Agents; Child; Child, Preschool; Double-Blind Method; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Infant; Male; Pediatrics; Peptic Ulcer; Proton Pump Inhibitors; Treatment Outcome; Wound Healing

The aim of the study was to evaluate erosive esophagitis healing and symptom improvement with once-daily esomeprazole in children ages 12 to 36 months with endoscopically or histologically proven gastroesophageal reflux disease (GERD).. Data from children ages 12 to 36 months were included in a post-hoc analysis of an 8-week, multicenter, randomized, and double-blind by dose strata study of patients ages 1 to 11 years with endoscopically or histologically confirmed GERD. Children were randomized to receive esomeprazole 5 or 10 mg once daily. Patients underwent endoscopy and, if required, mucosal biopsy at baseline. Patients who had erosive esophagitis (graded using the Los Angeles classification system) at baseline underwent a follow-up endoscopy at final study visit to assess healing of erosive esophagitis. Investigators scored severity of GERD symptoms at baseline and every 2 weeks using the Physician Global Assessment.. Thirty-one of 109 primary study patients ages 12 to 36 months were included in the post hoc analysis. At baseline, 15 patients (48.4%) had erosive esophagitis, underwent follow-up endoscopy, and were healed after 8 weeks of esomeprazole treatment. Of the 19 patients with moderate-to-severe baseline Physician Global Assessment symptom scores, 84.2% had lower scores by the final visit. Following esomeprazole treatment, GERD symptoms were significantly improved from baseline to final visit (P ≤ 0.0018).. Esomeprazole 5 or 10 mg may be used to successfully treat erosive esophagitis and symptoms of GERD in children as young as 1 year.Moreover, although not yet validated in pediatric patients, the Los Angeles classification system was useful in grading erosive esophagitis in children ages 12 to 36 months.

Topics: Anti-Ulcer Agents; Child, Preschool; Double-Blind Method; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Infant; Male; Pediatrics; Peptic Ulcer; Proton Pump Inhibitors; Treatment Outcome; Wound Healing

Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/ or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD.. In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5-10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5-10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded.. Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated.. The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy.

Topics: Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Infant; Male; Pediatrics; Proportional Hazards Models; Proton Pump Inhibitors; Treatment Outcome

BACKGROUND Refractory gastroesophageal reflux disease (GERD) may deteriorate patient quality of life (QOL) despite proton pump inhibitor (PPI) therapy. MATERIAL AND METHODS Nineteen Japanese institutions were surveyed to determine the clinical characteristics and QOL of patients with refractory GERD. Those patients treated with a conventional PPI were switched to 20 mg esomeprazole for 4 weeks. Symptoms and QOL were assessed using Global Overall Symptom and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires at baseline and at 2 and/or 4 weeks of esomeprazole treatment. RESULTS Of 120 patients who completed the survey, 58 (48.3%) had refractory GERD. Of these, 69.0% were aged ≥ 65 years, 79.3% were prescribed a PPI at a standard or high dose, and 22.4% were prescribed a PPI together with another drug. After switching to esomeprazole, patients reported significant improvements in heartburn, acid regurgitation, and excessive belching at 2 weeks using a symptom diary, as well as the total score, reflux, abdominal pain, and indigestion, which were assessed using the GSRS at 4 weeks. CONCLUSIONS About half of Japanese patients with GERD may be refractory to conventional PPIs. Their reflux-related symptoms are often severe and may impair QOL. Switching to esomeprazole could be used to improve their symptoms and QOL.

Topics: Adult; Aged; Aged, 80 and over; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Pantoprazole magnesium (pantoprazole-Mg) may display extended inhibition of the proton pump with the potential for improved clinical efficacy in gastro-oesophageal reflux disease (GERD).. To compare the efficacy of pantoprazole-Mg and esomeprazole in GERD.. Gastro-oesophageal reflux disease (Los Angeles grades A-D) patients were randomised to 4 weeks of treatment with pantoprazole-Mg (n = 290) or esomeprazole (n = 288), both 40 mg once daily, in this multicentre (14 Brazilian sites in 9 cities), double-blind study, with an additional 4 weeks' treatment in nonresponding patients. Severity of oesophagitis (at endoscopy) and GERD-related symptoms (ReQuest-GI) were assessed. The primary end point was the proportion of patients in complete remission (ReQuest-GI score <1.73 plus endoscopic healing) at week 4.. Complete remission occurred in 61% of patients in each treatment group at 4 weeks (primary endpoint) and in 81% and 79% of patients in the pantoprazole-Mg and esomeprazole groups at 8 weeks, with no significant differences. Mucosal healing rates were high and not significantly different. At 8 weeks, symptom relief with pantoprazole-Mg was significantly greater than that with esomeprazole (91.6% vs. 86.0%, P = 0.0370) because of continued improvement in symptoms with pantoprazole-Mg from week 4 to week 8 (P = 0.0206).. Pantoprazole-Mg 40 mg was at least as effective as esomeprazole 40 mg for complete remission and the mucosal healing rate was high. Symptom relief with pantoprazole-Mg continued to improve from 4 to 8 weeks and was greater than that with esomeprazole at week 8, suggesting an extended period of treatment effect (ClinicalTrials.gov identifier: NCT01132638).

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Anti-Ulcer Agents; Double-Blind Method; Endoscopy; Esomeprazole; Esophagitis; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pantoprazole; Proton Pump Inhibitors; Remission Induction; Treatment Outcome; Young Adult

To assess the performance of self-assessment gastroesophageal reflux disease questionnaire (GerdQ), 24-h impedance monitoring, proton pump inhibitor (PPI) test and intercellular space of esophageal mucosal epithelial cells in the diagnosis of gastroesophageal reflux disease (GERD).. Patients with symptoms suspected of GERD were administered the GerdQ and underwent endoscopy (measurement of intercellular space in the biopsy specimen sampling at 2 cm above the Z-line) and 24-h impedance pH monitoring, together with a 2-week experimental treatment with esomeprazole.. A total of 636 patients were included for the final analysis, including 352 with GERD. The sensitivity and specificity of GerdQ and 24-h impedance monitoring for diagnosing GERD were 57.7% and 48.9%, and 66.4% and 43.3%, respectively. The sensitivity of 24-h impedance pH monitoring increased to 93.7%. The sensitivity and specificity of dilated intercellular spaces (DIS) (≥0.9 μm) for diagnosing GERD were 61.2% and 56.1%, respectively, whereas those for PPI test were 70.5% and 44.4%.. GerdQ score or PPI test alone cannot accurately diagnose GERD in a Chinese population suspected of GERD. A definitive diagnosis of GERD still depends on endoscopy or 24-h pH monitoring. 24-h impedance pH monitoring may increase the sensitivity for diagnosing GERD by 20%; however, when used alone, it results in poor specificity in patients without acid suppressive therapy.

Topics: Adult; Anti-Ulcer Agents; Asian People; Biopsy; Electric Impedance; Endoscopes, Gastrointestinal; Esomeprazole; Esophageal pH Monitoring; Esophagus; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Mucous Membrane; Reproducibility of Results; Sensitivity and Specificity; Surveys and Questionnaires

Gastro esophageal reflux (GER) is common in cystic fibrosis (CF) and may contribute to lung disease. Approximately 50% of patients with cystic fibrosis are being treated with proton pump inhibitors (PPIs).. In a randomized controlled study in adults, we compared treatment with esomeprazole 40 mg twice daily versus placebo in patients with CF and frequent respiratory exacerbations over a thirty-six week treatment period to determine effect on time to first exacerbation and other health related outcomes.. 17 patients without symptoms of GER were randomized and 15 completed the study. 13 subjects underwent 24 hour ambulatory pH probe monitoring; 62% had pH probe evidence of GER. Forty one percent of subjects had a pulmonary exacerbation during the study. There was no significant difference in time to first pulmonary exacerbation (log rank test p = 0.3169). Five of nine subjects in the esomeprazole group compared with 2 of eight subjects in the placebo group experienced exacerbations (esomeprazole vs. placebo: odds ratio = 3.455, 95% CI = (0.337, 54.294), Fisher's exact test: p = 0.334). There was no change in Forced Expiratory Volume in one second, Gastroesophageal Symptom Assessment Score or CF Quality of Life score between the two treatment groups.. There was a trend to earlier exacerbation and more frequent exacerbations in subjects randomized to esomeprazole compared with placebo. The effect of proton pump inhibitors on pulmonary exacerbations in CF warrants further investigation.. Clinicaltrials.gov, NCT01983774.

Topics: Adult; Cystic Fibrosis; Disease Progression; Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Lung Diseases; Male; Proton Pump Inhibitors

This study was designed to demonstrate the safety and efficacy of esomeprazole combined with flupentixol/melitracen for the treatment of gastroesophageal reflux disease (GERD) patients with emotional disorders. METHODS Two hundred eighty-nine GERD patients with emotional disorders were divided randomly into two groups: group 1 received esomeprazole only (monotherapy) and group 2 received esomeprazole and flupentixol/melitracen (combination therapy). The patients' GERD questionnaire (GerdQ) and hospital anxiety and depression (HAD) scores were obtained before and after treatment. Changes in the scores, rates of symptom remission, and adverse effects were compared between the two groups.. After 2 weeks of treatment, the average decrease in GerdQ score in the combination group (4.04 ± 2.34) was significantly greater than that in the monotherapy group (3.34 ± 2.74; P < 0.05). Significant differences between the two groups were also found for changes in HAD anxiety scores (5.45 ± 2.41 vs 3.34 ± 2.43, P < 0.05), depression scores (5.47 ± 2.47 vs 3.00 ± 3.28, P < 0.05), and anxiety-depression scores (5.20 ± 2.71 vs 3.60 ± 2.56, P < 0.05). The remission of symptoms (eructation, abdominal pain, anorexia, and other accompanying symptoms) in the combination group was significantly better than that in the monotherapy group, and no significant difference in the incidence of adverse events was observed between the two groups.. The combination therapy has better efficacy than the monotherapy in improving the symptoms of gastroesophageal reflux in patients with emotional disorders. In addition, this combination treatment is safe, with a low incidence of adverse events.

Topics: Adult; Affective Symptoms; Anthracenes; Anxiety; Depression; Drug Combinations; Drug Therapy, Combination; Esomeprazole; Female; Flupenthixol; Gastroesophageal Reflux; Humans; Male; Middle Aged; Surveys and Questionnaires; Treatment Outcome

To assess the overall exposure after a single dose of esomeprazole in children with gastroesophageal reflux disease (GERD).. Oral esomeprazole administered as an intact capsule with 30 - 180 mL of water, or as an opened capsule mixed with as much as 1 tablespoon of applesauce followed by 30 - 180 mL of water.. In this randomized, open-label study of children aged 1 - 11 years with endoscopically proven GERD, patients weighing 8 - < 20 kg were randomized to a single 5- or 10-mg oral dose of esomeprazole, and patients weighing >= 20 kg were randomized to a single 10- or 20-mg oral dose of esomeprazole. Esomeprazole exposure (AUC(0-∞)), AUC from zero to last measurable concentration (AUC(0-t)), maximum plasma concentration (C(max)), time to C(max) (t(max)), terminal-phase half-life, apparent oral clearance, and apparent volume of distribution were determined.. 28 patients were randomized to receive esomeprazole: 14 patients weighing 8 to < 20 kg received esomeprazole 5 mg (n = 7) or 10 mg (n = 7), and 14 patients weighing ≥20 kg received esomeprazole 10 mg (n = 6) or 20 mg (n = 8). Children weighing 8 - < 20 kg had a 1.8-fold higher exposure with the 10-mg vs. 5-mg dose (AUC(0-∞), 1.32 vs. 0.73 μmol·h/L, respectively); children weighing ≥ 20 kg had a 4.4-fold higher exposure with the 20-mg vs. 10-mg dose (AUC(0-∞), 3.06 vs. 0.69 μmol·h/L). C(max) was 2.2-fold higher for the 10-mg vs. 5-mg dose (8 to < 20 kg) and 2.4-fold higher for the 20-mg vs.10-mg dose (>= 20 kg).. The pharmacokinetics of single-dose esomeprazole were dose-dependent in children weighing >= 20 kg but not in children weighing 8 to < 20 kg.

Topics: Anti-Ulcer Agents; Child; Child, Preschool; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Infant; Male

Functional dyspepsia (FD) is a gastroduodenal disorder that presents as postprandial fullness, early satiation, or epigastric burning despite no evidence of a structural disease. Proton pump inhibitors (PPIs) are often the first choice for treating FD. However, some patients need additional medication because of residual symptoms despite a certain level of benefit from the PPI. For these patients, a combination of PPI and other agents has a possibly more beneficial effect than changing their medication. This study aimed to evaluate the efficacy of an initial PPI followed by combination therapy with PPI and acotiamide in FD patients with residual symptoms after an initial PPI. We enrolled 105 patients who started an initial PPI (20 mg of esomeprazole once a day). Twenty-three patients with residual symptoms received 100 mg of acotiamide, a cholinesterase inhibitor, three times a day with esomeprazole as a combination therapy for 2 weeks. The symptoms were evaluated using the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (mFSSG). Eighteen of 23 patients (78%) achieved an overall improvement in symptoms. Almost all FD-related symptoms statistically improved after the combination therapy, with an improvement in the mFSSG score relevant to the postprandial distress syndrome and epigastric pain syndrome. The symptoms improved regardless of age, sex, and the pre-combination therapy score of the mFSSG. Our findings suggest that the combination therapy of acotiamide and PPI may be effective in selected FD patients with insufficient improvement with an initial PPI. However, well-designed trials are required to confirm the efficacy.

Topics: Benzamides; Drug Resistance; Drug Therapy, Combination; Dyspepsia; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Thiazoles; Treatment Outcome

Sleep disturbance is common in patients with GERD but there has been little evaluation of this problem in primary care in patients already taking therapy.. To evaluate the impact of administering a questionnaire (PASS test) to identify patients with sleep problems and evaluate the efficacy of esomeprazole to improve sleep disturbance in patients with GERD.. This was a primary care based cluster-randomised, open-label study where practices were assigned to intervention or control groups. PASS test failures continued current therapy (control) or were switched to 4 weeks' once-daily esomeprazole 20 or 40 mg (intervention). Patients were evaluated at the end of 4 weeks and the outcomes that were assessed were the sleep questions from the Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire and the presence or absence of sleep disturbance from the PASS test questionnaire.. A total of 1388 patients with evaluable data at 4 weeks were included in the analysis and 825 reported GERD-related sleep disturbance at baseline. At 4 weeks, 161 of 291 of control patients (55%) reported continued sleep disturbance compared to 120 of 534 (22.5%) of intervention patients [number needed to treat of 3: 95% confidence intervals (CI): 2.5-4]. There was a mean improvement in QOLRAD scores related to sleep in the intervention patients compared to control patients (mean improvement = 4.91; 95% CI: 3.73-6.09).. A PASS strategy identifies GERD patients with sleep disturbance in primary care that will benefit from a change in acid-suppressive therapy. ClinicalTrials.gov identifier: NCT00392002; study code: D9612L00096.

Topics: Adult; Aged; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Proton Pump Inhibitors; Quality of Life; Regression Analysis; Sleep Wake Disorders; Surveys and Questionnaires; Treatment Outcome

There are no prospective studies available on the behavior of extraesophageal and esophageal symptoms and treatment-related side effects in patients without effective antireflux medication, receiving the most effective antireflux medication, and after laparoscopic fundoplication.. Extraesophageal and esophageal reflux symptoms and treatment-related side effects were assessed in 60 patients while they were on no effective antireflux medication (three-week washout period), after three month of treatment with double-dose esomeprazole, and 3 months after laparoscopic Nissen fundoplication. Esophageal and extraesophageal reflux symptoms, rectal flatulence, and bloating were analyzed with the visual analog scale. In addition, dysphagia, rectal flatulence, and bloating were recorded as none, mild, moderate, or severe.. Both extraesophageal and esophageal reflux symptoms decreased after treatment with esomeprazole and were further reduced after fundoplication. Dysphagia and flatulence did not increase from baseline after surgery. Bloating decreased both after treatment with esomeprazole and after fundoplication. In contrast, dysphagia and increased flatus were found more often after surgery than during treatment with esomeprazole. Dysphagia and rectal flatulence were less common during treatment with esomeprazole than at baseline or after surgery.. Both extraesophageal and esophageal reflux symptoms decreased after treatment with esomeprazole and were reduced further after fundoplication. Any treatment-related side effect was not increased after surgery when compared to baseline. However, compared to esomeprazole there was more dysphagia and flatulence after fundoplication.

Topics: Esomeprazole; Female; Finland; Flatulence; Fundoplication; Gastroesophageal Reflux; Humans; Laparoscopy; Male; Proton Pump Inhibitors; Treatment Outcome

Combined with 24-h pH monitoring, the use of impedance is the most sensitive method available for detecting oesophageal reflux. Normal values for impedance have been previously established in healthy controls studied on and off proton pump inhibitors (PPI).. To determine the effects of PPIs on the total number of reflux episodes in the distal oesophagus measured by impedance in patients with and without gastro-oesophageal reflux disease (GERD).. In this prospective randomised double-blinded placebo controlled crossover study, all patients underwent two 24-h pH with impedance studies at least 2 weeks apart. Based on a randomisation scheme, patients received either 40 mg of esomeprazole twice daily for 1 week or identical capsule placebo for 1 week, then all patients were crossed over to the other treatment arm. GERD was defined by the validated Johnson-DeMeester score. Reflux by impedance was defined as a 50% decrease from baseline in retrograde movement of liquid between two impedance sites.. Sixty-three patients were enrolled and 41 patients completed the study [mean age 52 ± 12 years, 42% (17/41) men, 56% (23/41) Caucasian and 34% (14/41) African American]. Overall, there was no significant decrease in the total number of distal impedance episodes with esomeprazole compared with placebo (mean change 6.1 ± 22, P = 0.100). When analysed separately by GERD status, among GERD-positive patients, there was a significant decrease in distal impedance episodes while on esomeprazole compared with placebo (mean change -16 ± 22, P = 0.023), but not in GERD-negative patients (mean change -0.35 ± 20, P = 0.872).. Esomeprazole decreases significantly the number of reflux episodes detected by impedance, but only in patients with GERD.

Topics: Adult; Anti-Ulcer Agents; Cross-Over Studies; Double-Blind Method; Electric Impedance; Esomeprazole; Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Treatment Outcome

The aim of the study was to investigate whether hydrotalcite was comparable to esomeprazole, a proton pump inhibitor, in on-demand therapy for non-erosive reflux disease (NERD).. This was a multicenter, randomized, open-label clinical trial with initial and on-demand therapy. Patients who had complete symptom relief in the initial therapy were randomized to either hydrotalcite or esomeprazole in the on-demand therapy. The percentage of patients who quit on-demand therapy in the two groups and the cost-effectiveness of the treatment were evaluated as primary end points. The rate of symptom relief and the improvement of symptom score for initial therapy and the weekly average symptom score and weekly average number of days on treatment for on-demand therapy were evaluated as secondary end points.. In total, 398 patients were recruited in the initial therapy group, among whom 253 were included in on-demand therapy, with 127 patients in the hydrotalcite group and the remaining 126 in the esomeprazole group. 14 (11.0%) patients in the hydrotalcite group and six (4.8%) in the esomeprazole group quit the on-demand therapy due to unsatisfactory symptom control (P = 0.065). Cost-effectiveness calculated as the ratio of the cost of hydrotalcite to that of esomeprazole (per person/day) was 35.3% in the on-demand therapy. Similar number of patients achieved symptom relief in both groups.. Hydrotalcite is a good option of on-demand therapy for NERD patients due to its cost-effectiveness and speed of action.

Topics: Adolescent; Adult; Aged; Aluminum Hydroxide; Antacids; Anti-Ulcer Agents; Cost-Benefit Analysis; Drug Costs; Drug Therapy, Combination; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Magnesium Hydroxide; Male; Middle Aged; Proton Pump Inhibitors; Treatment Outcome; Young Adult

To evaluate the efficacy and safety of proton pump inhibitors in infants aged <1 year with gastroesophageal reflux disease (GERD).. In this randomized, double-blind, placebo-controlled multicenter study, neonates (premature to 1 month corrected age; n = 52) with signs and symptoms of GERD received esomeprazole 0.5 mg/kg or placebo once daily for up to 14 days. Change from baseline in the total number of GERD symptoms (from video monitoring) and GERD-related signs (from cardiorespiratory monitoring) was assessed with simultaneous esophageal pH, impedance, cardiorespiratory, and 8-hour video monitoring.. There were no significant differences between the esomeprazole and placebo groups in the percentage change from baseline in the total number of GERD-related signs and symptoms (-14.7% vs -14.1%, respectively). Mean change from baseline in total number of reflux episodes was not significantly different between esomeprazole and placebo (-7.43 vs -0.2, respectively); however, the percentage of time pH was <4.0 and the number of acidic reflux episodes >5 minutes in duration was significantly decreased with esomeprazole vs placebo (-10.7 vs 2.2 and -5.5 vs 1.0, respectively; P ≤ .0017). The number of patients with adverse events was similar between treatment groups.. Signs and symptoms of GERD traditionally attributed to acidic reflux in neonates were not significantly altered by esomeprazole treatment. Esomeprazole was well tolerated and reduced esophageal acid exposure and the number of acidic reflux events in neonates.

Topics: Administration, Oral; Analysis of Variance; Double-Blind Method; Drug Administration Schedule; Esomeprazole; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intention to Treat Analysis; Male; Monitoring, Physiologic; Proton Pump Inhibitors; Treatment Outcome

Gastro-oesophageal reflux disease (GORD) is suggested to cause or aggravate several respiratory conditions. Studies with proton pump inhibitors have resulted in only minor improvements in pulmonary outcomes in patients with GORD. It has been speculated that operative treatment of GORD might be more efficient as it also diminishes non-acidic reflux.. To compare the effects of esomeprazole 40 mg bid and fundoplication on airway responsiveness, forced expiratory volume in 1 s (FEV1), exhaled nitric oxide (NO) and respiratory symptoms in patients with moderate-to-severe GORD.. Sixty-nine GORD patients had methacholine inhalation challenge performed on them, and FEV1, exhaled NO and respiratory symptoms were measured at baseline, after a 3-month treatment with esomeprazole and 3 months after fundoplication. Primary outcome variable was dose-response slope (DRS), i.e. decline in FEV1 during methacholine challenge divided with the amount of methacholine administered (%/μmol). Pre-defined subgroup analysis was performed among those with concomitant asthma (n = 12).. There was no improvement in DRS, FEV1 or exhaled NO after esomeprazole treatment or fundoplication. Cough and dyspnoea measured with visual analog scale improved with esomeprazole treatment (P < 0.001), and further after fundoplication (P < 0.001). Among those with concomitant asthma, significant improvements in St George Respiratory Questionnaire (SGRQ) scores could be seen after fundoplication.. Neither esomeprazole treatment nor fundoplication diminishes airway responsiveness or exhaled NO, or improves FEV1 in patients with GORD. Improvements in respiratory symptoms and SGRQ scores after GORD treatments could be detected. However, as this was not a placebo-controlled study, the findings in these secondary endpoints should not be emphasised. ClinicalTrials.cov: NCT00994708.

Topics: Adult; Aged; Anti-Ulcer Agents; Asthma; Breath Tests; Bronchial Hyperreactivity; Esomeprazole; Female; Forced Expiratory Volume; Fundoplication; Gastroesophageal Reflux; Humans; Male; Middle Aged; Nitric Oxide; Treatment Outcome

Whether addition of prokinetics to proton pump inhibitors improves esophageal peristalsis and symptoms in patients with gastroesophageal reflux disease (GERD) remains unknown.. We evaluated the effect of mosapride, a 5-HT4 agonist, and PPI cotherapy in patients with GERD on esophageal motility using high-resolution manometry (HRM).. This study was designed as a double-blind, randomized, placebo-controlled trial. Patients with GERD were allocated to a group either taking 40 mg esomeprazole plus 30 mg mosapride or taking esomeprazole plus placebo. Symptom assessment and the HRM study were conducted before drug treatment and after 4 weeks.. Of 50 patients enrolled, 24 in the mosapride group (49 years old, 15 males) and 19 in the placebo group (43 years old, nine males) completed the study. Approximately 79 % of the patients had normal peristaltic function. Treatment response was not different between the two groups (79 vs. 68 %). Mosapride cotherapy tended to yield better response in patients with dyspepsia than those without dyspepsia (92 vs. 67 %). Lower esophageal sphincter pressure didn't change in both groups. Intrabolus pressure decreased in the mosapride group (3.4 ± 3.5 mmHg to 1.4 ± 4.1 mmHg, P < 0.05). Distal esophageal amplitude increased in the mosapride group and not in the placebo group (81 ± 34 to 89 ± 29 mmHg vs. 82 ± 32 to 83 ± 31 mmHg).. Adding mosapride on esomeprazole improved esophageal contractability and lowered intrabolus pressure in patients with GERD. Mosapride and esomeprazole cotherapy tended to yield better response in patients with concomitant dyspepsia.

Topics: Adult; Aged; Anti-Ulcer Agents; Benzamides; Double-Blind Method; Drug Therapy, Combination; Esomeprazole; Esophagus; Female; Gastroesophageal Reflux; Humans; Male; Manometry; Middle Aged; Morpholines; Peristalsis; Proton Pump Inhibitors; Serotonin Receptor Agonists

High-quality data regarding the efficacy of acid-suppressive treatment for unexplained chest pain are lacking. The aim of this study was to evaluate the efficacy of esomeprazole in primary-care treatment of patients with unexplained chest pain stratified for frequency of reflux/regurgitation symptoms.. Patients with a ≥ 2-week history of unexplained chest pain (unrelated to gastroesophageal reflux) who had at least moderate pain on ≥ 2 of the last 7 days were stratified by heartburn/regurgitation frequency (≤ 1 day/week (stratum 1) vs. ≥ 2 days/week (stratum 2)) and randomized to 4 weeks of double-blind treatment with twice-daily esomeprazole 40 mg or placebo. Chest pain relief during the last 7 days of treatment (≤ 1 day with minimal symptoms assessed daily using a 7-point scale) was analyzed by stratum in keeping with the predetermined analysis plan.. Overall, 599 patients (esomeprazole: 297, placebo: 302) were randomized. In stratum 1, more esomeprazole than placebo recipients achieved chest pain relief (38.7% vs. 25.5%; P=0.018); no between-treatment difference was observed in stratum 2 (27.2% vs. 24.2%; P=0.54). However, esomeprazole was superior to placebo in a post-hoc analysis of the whole study population (combined strata; 33.1% vs. 24.9%; P=0.035).. A 4-week course of high-dose esomeprazole provided statistically significant relief of unexplained chest pain in primary-care patients who experienced infrequent or no heartburn/regurgitation, but there was no such significant reduction in patients with more frequent reflux symptoms.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antacids; Chest Pain; Double-Blind Method; Drug Administration Schedule; Esomeprazole; Female; Gastroesophageal Reflux; Heartburn; Humans; Intention to Treat Analysis; Male; Middle Aged; Pain Measurement; Primary Health Care; Treatment Outcome; Young Adult

Although low-dose acetylsalicylic acid (ASA) is recommended for prevention of cardiovascular events in at-risk patients, its long-term use can be associated with the risk of peptic ulcer and upper gastrointestinal (GI) symptoms that may impact treatment compliance. This prespecified secondary analysis of the OBERON study (NCT00441727) determined the efficacy of esomeprazole for prevention/resolution of low-dose ASA-associated upper GI symptoms. A post hoc analysis of predictors of symptom prevention/resolution was also conducted. Helicobacter pylori-negative patients taking low-dose ASA (75-325 mg) for cardiovascular protection who had ≥1 upper GI risk factor were eligible. The patients were randomized to once-daily esomeprazole 40 mg, 20 mg, or placebo, for 26 weeks; 2303 patients (mean age 67.6 years; 36% aged >70 years) were evaluable for upper GI symptoms. The proportion of patients with dyspeptic or reflux symptoms (self-reported Reflux Disease Questionnaire) was significantly lower (P < 0.0001) in those treated with esomeprazole versus in those treated with placebo. Treatment with esomeprazole (P < 0.0001), age >70 years (P < 0.01), and the absence of upper GI symptoms at baseline (P < 0.0001) were all factors associated with prevention/resolution of upper GI symptoms. Together, these analyses demonstrate that esomeprazole is effective in preventing and resolving patient-reported upper GI symptoms in low-dose ASA users at increased GI risk.

Topics: Age Factors; Aged; Anti-Ulcer Agents; Aspirin; Cardiovascular Diseases; Dose-Response Relationship, Drug; Double-Blind Method; Dyspepsia; Esomeprazole; Female; Gastroesophageal Reflux; Gastrointestinal Diseases; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Secondary Prevention; Self Report; Upper Gastrointestinal Tract

Inadequate response to proton pump inhibitor (PPI) therapy in patients with gastroesophageal reflux disease (GERD) is reported in up to 40%. Patients with non erosive reflux disease (NERD) have lower response rates compared to patients with erosive reflux disease (ERD); pH metry contributes to GERD diagnosis and is critical for proper diagnosis of NERD. Aim of the study was to assess the need for doubling esomeprazole standard dose (40 mg) for 4 weeks in PPI naive patients with typical reflux symptoms and diagnosis of GERD based on endoscopy and 48 hours, wireless pH metry.. All patients underwent upper GI endoscopy. Symptoms were recorded with a structured questionnaire (RDQ) and acid exposure was determined by 48 hours, wireless pH monitoring (BRAVO). In case of abnormal acid exposure, patients received a short term treatment with esomeprazole 40 mg q.d. for 4 weeks. If symptoms persisted, patients underwent a second pH metry on PPI and the dose was increased to 40 mg b.i.d.. 31 consecutive patients with typical reflux symptoms underwent 48 hours pH monitoring. 22 patients (71%) had abnormal acid exposure, 9 patients had normal pH metry (29%). Of the 9 patients with normal pH metry, 2 were found with erosive esophagitis and 7 without endoscopic abnormalities. 24 patients with documented GERD received esomeprazole treatment. 21 patients achieved complete symptom resolution with 40 mg q.d. after 4 weeks (88%). Only 2 patients required doubling the dose of esomeprazole for complete symptom resolution, 1 patient remained with symptoms.. Patients with typical reflux symptoms and abnormal acid exposure have a high response rate to standard dose esomeprazole regardless of whether they have ERD or NERD.

Topics: Adolescent; Adult; Aged; Dose-Response Relationship, Drug; Esomeprazole; Esophageal pH Monitoring; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Proton Pump Inhibitors; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Treatment Outcome; Young Adult

The aim of this study was to assess whether the efficacy of proton pump inhibitors (PPI) therapy at a standard dose in esophageal acid control is affected by the presence of hiatus hernia in Chinese gastroesophageal reflux disease patients, and whether a higher dose of PPI is required for acid control.. Consecutive gastroesophageal reflux disease patients who had typical reflux symptoms and abnormal baseline 24-h esophageal pH and underwent upper endoscopy were enrolled to receive esomeprazole at 40 mg once daily for 4 weeks. Patients underwent the dual-channel 24-h pH test at the end of 4-week therapy. If the 24-h esophageal pH was still abnormal at the end of 4-week therapy, then esomeprazole at 40 mg twice daily was given for another 4 weeks after a washout interval of 1 week, and a 24-h pH test was repeated at the end of the therapy.. Overall, 76 patients were included, 13 with hiatus hernia. Of the 76 patients treated with a 40 mg of esomeprazole daily, esophageal acid exposure was normalized in 64 (84.2%). Normalization of acid exposure was achieved by standard PPI therapy in 53.2% (7/13) of patients with hiatus hernia and 90.5% (57/63) of those without (P = 0.004). A double dose of esomeprazole was successful in normalizing the esophageal pH in all 12 non-responders to the standard dose of esomeprazole, including the six patients with hiatus hernia and six patients without.. The standard-dose of esomeprazole fails to normalize the esophageal pH in almost 50% of patients with hiatus hernia, in whom the "double-dose" esomeprazole therapy is required.

Topics: Adult; Aged; Asian People; Chi-Square Distribution; China; Esomeprazole; Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Gastroscopy; Hernia, Hiatal; Humans; Male; Middle Aged; Proton Pump Inhibitors; Statistics, Nonparametric; Time Factors

Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD.. In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5-10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5-10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded.. Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated.. The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy.

Topics: Chi-Square Distribution; Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Infant; Kaplan-Meier Estimate; Male; Proportional Hazards Models; Proton Pump Inhibitors; Treatment Outcome

Several oral proton pump inhibitors (PPIs) are currently approved for use in pediatric patients in North America and Europe. However, when use of oral therapy is not possible or appropriate, intravenous formulations of PPIs may be helpful. Intravenous esomeprazole is approved in the United States for the short-term treatment of gastroesophageal reflux disease (GERD) with erosive esophagitis in adults and in pediatric patients 1 month to 17 years of age (inclusive) as an alternative to oral therapy. Four open-label, randomized, 2-way crossover studies in adults with GERD found no clinically relevant differences in acid suppression between repeated doses of oral and intravenous esomeprazole. However, the pharmacokinetics of intravenous esomeprazole has not been studied extensively in children.. The aim of this study was to evaluate steady-state pharmacokinetics and tolerability of repeated doses of intravenous esomeprazole in children.. In this multicenter, open-label study, hospitalized patients (0-17 years of age) considered for acid suppression therapy received once-daily intravenous esomeprazole sodium for injection at 0.5 mg/kg (0-1 month of age), 1.0 mg/kg (1-11 months of age), 10 mg (1-5 years of age), 10 or 20 mg (6-11 years of age), or 20 or 40 mg (12-17 years of age) for 4 days. Children 6 to 11 years of age (inclusive) were randomized in a 1:1 ratio to receive esomeprazole 10 or 20 mg, and adolescents 12 to 17 years of age (inclusive) were randomized in a 1:1 ratio to receive esomeprazole 20 or 40 mg. Blood samples were drawn pre- and post-dose. Plasma esomeprazole was measured using reversed-phase liquid chromatography and mass spectrometry. Pharmacokinetic variables were derived using mixed-effects modeling. Adverse events (AEs) were assessed.. Fifty-nine patients were randomized and 57 received the study drug. A majority of patients were white (44 white, 5 black/African American, 3 Asian, 5 other) and male (35/57). Fifty patients were eligible for pharmacokinetic analysis, including 6 to 8 patients in each age group. Esomeprazole pharmacokinetics was dose proportional and related to weight and age. Clearance increased with increasing weight and age. The mean AUC(τ) ranged from 6.9 μmol · h/L (10 mg, 6-11 years) to 17.6 μmol · h/L (40 mg, 12-17 years). The mean C(ss,max) ranged from 3.7 μmol/L (0.5 mg/kg, 0-1 month) to 10.5 μmol/L (40 mg, 12-17 years). Thirty-one patients experienced 1 or more AEs; 6 patients experienced 1 or more treatment-unrelated serious AEs.. Intravenous esomeprazole at doses resulting in targeted AUC(τ) and C(ss,max) similar to therapeutic exposure in adults appeared to be reasonably well tolerated in this small, select pediatric population. ClinicalTrials.gov identifier: NCT00474019.

Topics: Adolescent; Age Factors; Area Under Curve; Child; Child, Preschool; Chromatography, Liquid; Chromatography, Reverse-Phase; Dose-Response Relationship, Drug; Drug Administration Schedule; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Infant; Infant, Newborn; Injections, Intravenous; Male; Mass Spectrometry; Metabolic Clearance Rate; Proton Pump Inhibitors

Sustained acid inhibition with PPI stimulates gastrin secretion, exerting a proliferative drive on enterochromaffin-like cells (ECL cells) of the oxyntic mucosa. It may also accelerate development of gastric gland atrophy in Helicobacter pylori-infected individuals.. To evaluate gastric exocrine and endocrine cell changes in GERD patients randomised to laparoscopic antireflux surgery (LARS, n = 288) or long-term (5 years) esomeprazole (ESO) treatment (n = 266).. Antral and corpus biopsies were taken at endoscopy and serum gastrin and chromogranin A levels were assayed, at baseline and after 1, 3 and 5 years' therapy.. Biopsies were available at each time point for 158 LARS patients and 180 ESO patients. In H. pylori-infected subjects, antral mucosal inflammation and activity improved significantly (P < 0.001) and stabilised after 3 years on esomeprazole while no change in inflammation was observed after LARS. Oxyntic mucosal inflammation and activity remained stable on esomeprazole but decreased slightly over time after LARS. Neither intestinal metaplasia nor atrophy developed in the oxyntic mucosa. ECL cell density increased significantly after ESO (P < 0.001), corresponding with an increase in circulating gastrin and chromogranin A. After LARS, there was a significant decrease in ECL cell density (P < 0.05), accompanied by a marginal decrease in gastrin and chromogranin.. Antral gastritis improved in H. pylori-infected GERD patients after 5 years on esomeprazole, with little change in laparoscopic antireflux surgery patients, who acted as a control. Despite a continued proliferative drive on enterochromaffin-like cells during esomeprazole treatment, no dysplastic or neoplastic lesions were found and no safety concerns were raised. NCT 00251927.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Chromogranin A; Enterochromaffin-like Cells; Esomeprazole; Female; Follow-Up Studies; Gastric Acid; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Laparoscopy; Male; Middle Aged; Proton Pump Inhibitors; Time Factors; Treatment Outcome; Young Adult

Cough may be a manifestation of gastro-oesophageal reflux disease (GERD). The utility of acid suppression in GERD-related cough is uncertain.. To assess the impact of high-dose acid suppression with proton pump inhibitors (PPI) on chronic cough in subjects with rare or no heartburn.. Subjects were nonsmokers without history of asthma, with chronic cough for >8 weeks. All subjects underwent a baseline 24-h pH/impedance study, methacholine challenge test and laryngoscopy. Subjects were randomised to either 40 mg of esomeprazole twice daily or placebo for 12 weeks. The primary outcome measure was the Cough-Specific Quality of Life Questionnaire (CQLQ). Secondary outcomes were response on Fisman Cough Severity/Frequency scores and change in laryngeal findings.. Forty subjects were randomised (22 PPI, 18 placebo) and completed the study. There was no difference between PPI and placebo in CQLQ (mean improvement 9.8 vs. 5.9 respectively, P = 0.3), or Fisman Cough Severity/Frequency scores. Proportion of patients who improved by >1 s.d. on the CQLQ was 27.8% (five of 18) and 31.8% (seven of 22) in the placebo and PPI groups respectively.. In subjects with chronic cough and rare or no heartburn, high-dose proton pump inhibitor does not improve cough-related quality of life or symptoms.

Topics: Adolescent; Adult; Aged; Chronic Disease; Cough; Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Severity of Illness Index; Statistics as Topic; Treatment Outcome; Young Adult

Generic omeprazole has been approved in many countries for the treatment of acid-related gastrointestinal disorders. However, clinical studies comparing generic to original proton pump inhibitors are limited.. To compare the effect of generic omeprazole 20 mg/day with esomeprazole 20 mg/day on intragastric acidity and to investigate the influence of the CYP2C19 metabolizer status.. In this randomised, single-blinded, two-way crossover study, 24 healthy Helicobacter pylori-negative subjects, received generic omeprazole (Omep; Hexal AG, Holzkirchen, Germany) 20 mg once daily or esomeprazole 20 mg once daily for five consecutive days. Twenty-four-hour intragastric pH was recorded on day 5 of each treatment. CYP2C19 status was determined by polymerase chain reaction-restriction fragment length polymorphism.. Over all, there were no statistically significant differences between generic omeprazole and esomeprazole with respect to median intragastric pH (3.5 and 3.9, P = 0.07), the total hours with intragastric pH >4 (10.4 and 11.3, P = 0.29), and during upright (9.6 and 9.1, P = 0.77) or supine (2.2 and 2.2, P = 0.94) position. However, in CYP2C19 rapid metabolizers, esomeprazole was superior to omeprazole, with the percentage of time with intragastric pH >3.0 and pH >3.5 being higher with esomeprazole than with generic omeprazole [Δ = 9% (P = 0.026) and Δ = 8% (P = 0.046), respectively].. Overall, generic omeprazole 20 mg appears to provide a similar intragastric acid control when compared with esomeprazole 20 mg. However, esomeprazole might be advantageous in subjects with a rapid CYP2C19 metabolizer status.

Topics: Adolescent; Adult; Anti-Ulcer Agents; Aryl Hydrocarbon Hydroxylases; Cross-Over Studies; Cytochrome P-450 CYP2C19; Drugs, Generic; Enzyme Inhibitors; Esomeprazole; Female; Gastric Acid; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Omeprazole; Statistics as Topic; White People; Young Adult

Despite the high prevalence of gastro-oesophageal reflux disease (GORD) and the documented impact of GORD symptoms on individual health-related quality of life (HR-QOL) and on socioeconomic factors, structured management of GORD has had a low priority in Swedish routine primary health care.. The primary objective of this study (IMPROVE) was to evaluate the effects of a structured follow-up and management regimen for primary-care GORD patients with symptomatic breakthrough despite standard proton pump inhibitor (PPI) treatment. Patients received either an increased dose of current PPI treatment or were switched to the more effective acid inhibitor esomeprazole.. GORD patients with symptomatic breakthrough despite standard PPI treatment were identified through medical records and by a postal survey using the GERD Impact Scale (GIS) questionnaire. Patients rated the severity and frequency of GORD symptoms, general health status (EuroQol Group 5-Dimension Self-Report Questionnaire) and the impact of GORD symptoms on work productivity (Work Productivity and Activity Impairment) before and 4 weeks following randomization to open-label treatment with either increased acid suppressive therapy or an adjusted, higher dosage of the PPI previously used. The patients' valuation, in monetary terms, of the treatment they received pre-study versus the treatment given during the study was documented through willingness-to-pay (WTP) questions.. Following more effective acid suppression, 66.3% of the study population experienced complete relief of heartburn, with no difference between the groups; HR-QOL was restored to a level comparable to that of a normal Swedish population and ability to work efficiently was significantly improved. Access to a better acid suppressive treatment was highly valuable to the patients in terms of WTP.. An improved GORD management strategy including structured follow-up of treatment given and initiation of more effective acid inhibitor therapy when symptoms persist will be of great benefit to GORD patients. [ClinicalTrials.gov Identifier: NCT00272701].

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Efficiency; Esomeprazole; Female; Follow-Up Studies; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Primary Health Care; Proton Pump Inhibitors; Quality of Life; Surveys and Questionnaires; Sweden; Young Adult

Acute stress exacerbates heartburn in gastroesophageal reflux disease (GERD) patients by enhancing the perceptual responses to intraesophageal acid. The aim of the study was to determine if antireflux treatment can still alter stimulus response functions to acid in patients undergoing acute stress as compared with placebo.. Symptomatic GERD patients with erosive esophagitis (EE) or an abnormal pH test were included. Patients underwent stimulus response functions to intraesophageal acid perfusion using the mental arithmetic stressor test. Thereafter, patients were randomized (2 : 1 ratio) to either esomeprazole 40 mg once daily or placebo for 8 weeks. On the last day of treatment, subjects underwent stimulus response functions to intraesophageal acid perfusion using a similar stressor as baseline.. A total of 31 patients were randomized into the treatment arm (mean age 48.6 ± 2.8, M/F 21/10) and 16 into the placebo arm (mean age 52.3 ± 4.3, M/F 12/4). In the esomeprazole group, there was a significant increase in lag time to symptom perception (P = 0.02) and decreased in intensity rating (P = 0.01) as well as acid perfusion sensitivity score (P = 0.01). There was no significant difference in any of the stimulus response functions to acid in the placebo group between baseline and treatment. Interpersonal sensitivity was the only independent clinical predictor factor for response to antireflux treatment.. Long-term antireflux treatment with a proton pump inhibitor is effective in reducing esophageal perception responses to acid during acute stress.

Topics: Anti-Ulcer Agents; Esomeprazole; Esophageal pH Monitoring; Esophagus; Gastroesophageal Reflux; Humans; Hydrochloric Acid; Placebos; Quality of Life; Stress, Psychological; Surveys and Questionnaires

Evidence suggests that rates of gastroesophageal reflux disease are increasing in the Asia-Pacific region, where patients tend to have predominantly non-erosive reflux disease as opposed to erosive (reflux) esophagitis. At present, data for the responsiveness of non-erosive reflux disease to proton pump inhibition are scant. We aimed to study esomeprazole for the treatment of non-erosive reflux disease in Chinese patients.. Patients with a clinical diagnosis of gastroesophageal reflux, and a locally validated reflux index, the Chinese GerdQ, of equal to or greater than 12 were recruited and randomized to receive esomeprazole 20 mg daily or placebo for 8 weeks. Reflux index scores, quality of life (SF-36), and the hospital anxiety and depression (HAD) scale and symptom relief were evaluated before, during, and after treatment.. A total of 175 patients were randomized. Patients in the esomeprazole group (n = 85) demonstrated statistically significant reductions in their GerdQ index, from 19.45 to 15.37 and to 14.32 (p = 0.013, p = 0.005) at weeks 4 and 8, respectively. Compared to placebo at week 8, 57.1% of patients on esomeprazole found that their symptoms had resolved or were acceptable compared with 37.2% in the placebo group (p = 0.001). There were no statistically significant differences in overall quality-of-life measures or the HAD scale related to treatment.. This study suggests that esomeprazole is efficacious in treating Chinese patients with non-erosive reflux disease.

Topics: Adolescent; Adult; Aged; Anxiety; China; Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Young Adult

Gastroesophageal reflux disease (GERD) is a chronic, relapsing disease with symptoms that have negative effects on daily life. Two treatment options are long-term medication or surgery.. To evaluate optimized esomeprazole therapy vs standardized laparoscopic antireflux surgery (LARS) in patients with GERD.. The LOTUS trial, a 5-year exploratory randomized, open, parallel-group trial conducted in academic hospitals in 11 European countries between October 2001 and April 2009 among 554 patients with well-established chronic GERD who initially responded to acid suppression. A total of 372 patients (esomeprazole, n = 192; LARS, n = 180) completed 5-year follow-up. Interventions Two hundred sixty-six patients were randomly assigned to receive esomeprazole, 20 to 40 mg/d, allowing for dose adjustments; 288 were randomly assigned to undergo LARS, of whom 248 actually underwent the operation.. Time to treatment failure (for LARS, defined as need for acid suppressive therapy; for esomeprazole, inadequate symptom control after dose adjustment), expressed as estimated remission rates and analyzed using the Kaplan-Meier method.. Estimated remission rates at 5 years were 92% (95% confidence interval [CI], 89%-96%) in the esomeprazole group and 85% (95% CI, 81%-90%) in the LARS group (log-rank P = .048). The difference between groups was no longer statistically significant following best-case scenario modeling of the effects of study dropout. The prevalence and severity of symptoms at 5 years in the esomeprazole and LARS groups, respectively, were 16% and 8% for heartburn (P = .14), 13% and 2% for acid regurgitation (P < .001), 5% and 11% for dysphagia (P < .001), 28% and 40% for bloating (P < .001), and 40% and 57% for flatulence (P < .001). Mortality during the study was low (4 deaths in the esomeprazole group and 1 death in the LARS group) and not attributed to treatment, and the percentages of patients reporting serious adverse events were similar in the esomeprazole group (24.1%) and in the LARS group (28.6%).. This multicenter clinical trial demonstrated that with contemporary antireflux therapy for GERD, either by drug-induced acid suppression with esomeprazole or by LARS, most patients achieve and remain in remission at 5 years.. clinicaltrials.gov Identifier: NCT00251927.

Topics: Adult; Anti-Ulcer Agents; Chronic Disease; Digestive System Surgical Procedures; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Laparoscopy; Male; Middle Aged; Remission Induction; Severity of Illness Index; Treatment Outcome

Esophageal multichannel intraluminal impedance (MII) allows measurement of the conductivity of adjacent contents. During esophageal rest, raw impedance levels may represent mucosal integrity. We assessed the influence of proton pump inhibitors (PPIs) on presumed mucosal integrity by reanalyzing raw MII levels of 21 pH-MII tracings from infants with gastroesophageal reflux (GER) disease before and after esomeprazole treatment. Median (interquartile range) esophageal MII increased during treatment, 938 (652-1304) versus 1885 (1360-2183) Ohm, P < 0.0001. Patients with lower MII levels demonstrated a larger increase on therapy: Spearman r2 = 0.28, P = 0.014. No correlation with standard GER parameters was observed. In conclusion, PPI therapy increases MII levels in infants with symptomatic GER disease.

Topics: Anti-Ulcer Agents; Biomarkers; Cohort Studies; Electric Conductivity; Electrochemical Techniques; Esomeprazole; Esophagus; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Infant, Newborn; Infant, Premature; Mucous Membrane; Proton Pump Inhibitors; Severity of Illness Index

Gastro-oesophageal reflux has been implicated in the pathogenesis of chronic cough. Guidelines on management suggest a therapeutic trial of anti-reflux medication. Esomeprazole is a proton pump inhibitor licensed for the long-term treatment of acid reflux in adults and we compared the effects of esomeprazole and placebo on patients with chronic cough.. This was a prospective, single-centre, randomized, double-blind, placebo-controlled, parallel group study conducted over 8weeks. Fifty adult non-smokers with chronic cough and normal spirometry were randomized. Patients completed cough-related quality-of-life and symptom questionnaires and subjective scores of cough frequency and severity at the beginning and end of the study. They also kept a daily diary of symptom scores. Citric acid cough challenge and laryngoscopic examination were performed at baseline and the end of the study. The primary outcome was improvement in cough score.. There were no differences in cough scores in the placebo and treatment arms of the study although some significant improvements were noted when compared to baseline. In the cough diary scores there was a trend towards greater improvement in the treatment arm in patients with dyspepsia.. Esomeprazole did not have a clinically important effect greater than placebo in patients with cough. It suggests a marked placebo effect in the treatment of cough.

Topics: Chronic Disease; Cough; Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Gastroesophageal reflux disease (GERD) is a chronic condition that usually requires long-term maintenance therapy with proton-pump inhibitors (PPIs). In clinical practice, patients receive PPIs at the lowest dose to control symptoms. However, it is not known whether this approach adequately controls acidic esophageal reflux. We sought to investigate the efficacy of three different dosages of esomeprazole in patients receiving maintenance therapy for GERD, using the Bravo pH system.. Patients with a previous history of erosive esophagitis A or B (LA classification) that was healed at the time of enrollment or endoscopy-negative reflux disease (ENRD), documented with an abnormal pH study, were randomized to receive maintenance therapy with esomeprazole 40 mg twice daily (group A), once daily (group B), or every other day (group C). Intraesophageal pH was monitored for two consecutive days using the Bravo wireless system, 30 days after randomization. The parameters subjected to analysis were percent of total time pH<4 and the De Meester score.. The pH results from 73 patients (group A=24, group B=24, group C=25 patients) were subjected to final analysis. On the first day of the study, the mean (+/-s.d.) percent of total time pH <4 and the De Meester score were group A: 0.9(1.2) and 4.1(4.0); group B: 1.5(1.6) and 7.0(6.9); group C: 1.3(1.0) and 6.0(3.3), respectively (P=0.262 and 0.134, respectively). On the second day of the study, the corresponding values were group A: 0.7(1.0) and 3.9(5.9); group B: 1.5(1.8) and 6.4(6.6); group C: 7.0(4.4) and 29.4(19.4), respectively. The difference was statistically significant (P<0.0001 and <0.0001, respectively). Further analysis showed that patients not receiving PPI had a significantly higher mean percent of total time pH<4 and De Meester score as compared with patients on PPI once or twice daily (P<0.001 and <0.001 respectively).. The administration of esomeprazole 40 mg every other day does not control acidic esophageal reflux on the day off PPI. Esomeprazole 40 mg once daily effectively controls reflux of acid in patients with history of mild esophagitis or ENRD, whereas doubling the dose does not seem to confer any further advantage.

Topics: Adult; Dose-Response Relationship, Drug; Drug Administration Schedule; Esomeprazole; Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Treatment Outcome

Gastroesophageal reflux disease (GERD)-associated changes in esophageal histology have been reported mainly after short-term medical antireflux therapy, and few individual lesions have been examined. We report detailed histological findings from the LOTUS study, at baseline and at 1 and 3 years after laparoscopic antireflux surgery (LARS) or esomeprazole treatment in patients with chronic GERD.. LOTUS is a long-term, open, parallel-group, multicenter, randomized, controlled trial conducted in 11 European countries that compared LARS (n=248) with esomeprazole 20-40 mg daily (n=266). Biopsies from the distal esophagus 2 cm above the Z-line and at the Z-line were taken at baseline, and 1 and 3 years. The following lesions were assessed: basal cell hyperplasia (BCH), papillary elongation (PE), intercellular space dilatations (ISDs), intraepithelial eosinophils (EOSs), neutrophils, and necrosis/erosion. A severity score (SS, range 0-2) was calculated by taking the average score of all assessable lesions.. All lesions were more severe on Z-line biopsies than at 2 cm, and almost all improved significantly from baseline to 1 and 3 years. The average SS (from 2 cm to Z-line) changed from 0.95 to 0.57 (1 year) and to 0.49 (3 years) on esomeprazole, and from 0.91 to 0.56 (1 year) and to 0.52 (3 years) after LARS (P<0.001 for both treatments at 1 and 3 years, with no significant difference between treatments). The proportions of patients with severe histological changes decreased from approximately 50% at baseline to 11% at 3 years.. Both continuous esomeprazole treatment and laparoscopic fundoplication are associated with significant and similar overall improvement in microscopic esophagitis after 1 year that is maintained at 3 years.

Topics: Adult; Age Distribution; Biopsy, Needle; Chronic Disease; Esomeprazole; Esophageal pH Monitoring; Esophagitis, Peptic; Esophagoscopy; Female; Follow-Up Studies; Fundoplication; Gastroesophageal Reflux; Humans; Immunohistochemistry; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Probability; Risk Assessment; Severity of Illness Index; Sex Distribution; Statistics, Nonparametric; Time Factors; Treatment Outcome

Gastroesophageal reflux disease (GERD) is common among patients with asthma; however, studies investigating the effect of proton pump inhibitors on asthma outcomes report conflicting results.. To investigate the effect of esomeprazole 40 mg once or twice daily on asthma outcomes in patients with concomitant symptoms of GERD.. This 26-week, randomized, double-blind, placebo-controlled study (NCT00317044) included adult patients (18-70 yr) with moderate-to-severe asthma and symptomatic GERD. The change in morning peak expiratory flow (primary variable), evening peak expiratory flow, FEV(1), asthma symptoms, Asthma Quality of Life Questionnaire, Reflux Disease Questionnaire, and tolerability were assessed.. A total of 961 patients were randomized and 828 completed the study. Relative to baseline, improvement in morning peak expiratory flow was observed for both esomeprazole 40 mg once daily (+3.5 L/min; 95% CI, -3.2 to 10.2) and 40 mg twice daily (+5.5 L/min; 95% CI, -1.2 to 12.2), although no statistically significant between-treatment differences were apparent. At treatment end, both doses of esomeprazole significantly improved FEV(1) versus placebo (+0.09 L and +0.12 L; P = 0.0039 and P < 0.0001, respectively). However, only esomeprazole 40 mg twice daily demonstrated a significant improvement when FEV(1) was calculated over the entire 26-week period (+0.07 L; P = 0.0042). Significant improvements in Asthma Quality of Life Questionnaire total score were demonstrated for both esomeprazole doses compared with placebo (+0.28 and +0.41; P = 0.0006 and P < 0.0001, respectively).. Esomeprazole may improve pulmonary function and asthma-related quality of life. However, the improvements were minor and of small clinical significance.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Asthma; Double-Blind Method; Esomeprazole; Female; Forced Expiratory Volume; Gastroesophageal Reflux; Humans; Male; Middle Aged; Placebos; Proton Pump Inhibitors; Sickness Impact Profile; Spirometry; Young Adult

The aim of this study was to compare acid control with a once-daily (od) modified-release (MR) formulation of esomeprazole vs. the conventional formulation (CF) dosed twice-daily (bid).. In a randomized, five-way crossover study, 55 healthy volunteers underwent 24-h intragastric pH monitoring after 5-day treatment with MR esomeprazole (40, 60 or 80 mg od) and CF esomeprazole (20 or 40 mg bid).. Modified-release 60 and 80 mg od resulted in a significantly longer time with intragastric pH > 4 than MR 40 mg od (77.1 and 79.0% vs. 66.4%, respectively; both p < 0.05). At equivalent total daily doses, CF 20 mg bid led to a significantly longer time with intragastric pH > 4 than MR 40 mg od (72.3 vs. 66.4%; p < 0.05), and CF 40 mg bid led to a significantly longer time with pH > 4 than MR 80 mg od (85.5 vs. 79.0%; p < 0.05).. At equivalent total daily doses, the MR formulation of esomeprazole provides less 24-h acid control than the conventional formulation dosed twice-daily.

Topics: Adult; Cross-Over Studies; Delayed-Action Preparations; Esomeprazole; Female; Gastric Acid; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors

Hispanic-Americans are a rapidly growing population in the United States, yet gastro-oesophageal reflux disease (GERD) is not well studied in this population.. To compare the efficacy of esomeprazole, lansoprazole and pantoprazole in suppressing gastric acid, including the area of the 'acid pocket,' in Hispanics with GERD.. In this open-label, 3-way crossover study, 83 Hispanics with symptomatic GERD were randomized to 1 of 6 possible treatment sequences of three 5-7-day dosing periods with esomeprazole 40 mg, lansoprazole 30 mg and pantoprazole 40 mg daily separated by 10-17-day washout periods. Intragastric pH was measured for 24 h using dual probes with a distal and proximal (area of the 'acid pocket') electrode.. Esomeprazole suppressed intragastric acid (pH >4.0) significantly longer over 24 h (primary end point) compared with lansoprazole and pantoprazole (P < 0.0001), and proximal gastric acid (pH >4.0) significantly longer over 24 h compared with lansoprazole (P < 0.05) and pantoprazole (P < 0.0001).. Esomeprazole was more effective than lansoprazole and pantoprazole in suppressing gastric acidity at both intragastric distal and proximal (area of the acid pocket) sites in Hispanics with GERD. Future studies are warranted to understand better the role of the acid pocket in GERD (Clinical trial numbers: D9612L00106; ClinicalTrials.gov: NCT00410592).

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Anti-Ulcer Agents; Cross-Over Studies; Drug Therapy, Combination; Esomeprazole; Female; Gastric Acid; Gastroesophageal Reflux; Hispanic or Latino; Humans; Lansoprazole; Male; Middle Aged; Pantoprazole; Patient Compliance; Treatment Outcome; United States; Young Adult

Nighttime heartburn, common among patients with gastro-oesophageal reflux disease (GERD), is associated with substantial clinical effects. GERD-related sleep disturbances are underappreciated and undertreated.. To evaluate the efficacy of esomeprazole on GERD-related nighttime heartburn and associated sleep disturbances.. In this multicentre, randomized, double-blind, placebo-controlled study, patients with moderate-to-severe nighttime heartburn and GERD-related sleep disturbances (endoscopies not required) received esomeprazole 20 mg or placebo each morning for 4 weeks. Heartburn symptoms and GERD-related sleep disturbances were evaluated using the validated Pittsburgh Sleep Quality Index and validated Work Productivity and Activity Impairment Questionnaire.. The analysis included 262 patients (esomeprazole, n = 137; placebo, n = 125). Significantly more patients receiving esomeprazole achieved nighttime heartburn relief (primary end point) than those receiving placebo (34.3% vs. 10.4%; P < 0.0001). Secondary end points such as relief of GERD-related sleep disturbances (P = 0.006), days without GERD-related sleep disturbances (P = 0.0003) and complete resolution of sleep disturbances (P < 0.0001) favoured esomeprazole over placebo. Sleep quality, work productivity and regular daily activities also improved significantly with esomeprazole vs. placebo.. Esomeprazole 20 mg is effective for patients with moderate-to-severe nighttime heartburn and GERD-related sleep disturbances, improving heartburn symptoms, sleep quality, work productivity and functionality.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Prospective Studies; Sleep Wake Disorders; Surveys and Questionnaires; Treatment Outcome; Young Adult

The aim of this study was to determine the accuracy of the diagnosis of gastro-oesophageal reflux disease (GORD) by the Reflux Disease Questionnaire (RDQ), family practitioners, gastroenterologists and a test of esomeprazole therapy.. This was a single-blind, single-arm study over 3-4 weeks from September 2005 to November 2006. Each symptom-based diagnostic assessment was made blinded to prior diagnoses. Patients were those presenting to their family practitioner with troublesome upper gastrointestinal symptoms (n=308). The RDQ was completed and a symptom-based diagnosis was made by the family practitioner. Placebo esomeprazole was started. Gastroenterologists made a symptom-based diagnosis and then performed endoscopy with 48 h oesophageal pH and symptom association monitoring to determine the presence/absence of GORD. Symptoms were recorded during treatment with 40 mg of esomeprazole for 2 weeks. The main outcome measure was RDQ scoring for the presence of GORD compared with symptom-based diagnosis by family physicians and gastroenterologists.. GORD was present in 203/308 (66%) patients. Only 49% of the patients with GORD selected either heartburn or regurgitation as the most troublesome symptom. Sensitivity and specificity, respectively, of the symptom-based diagnosis of GORD, were 62% and 67% for the RDQ, 63% and 63% for family practitioners, and 67% and 70% for gastroenterologists. Symptom response to esomeprazole was neither sensitive nor specific for the diagnosis of GORD.. The RDQ, family practitioners and gastroenterologists have moderate and similar accuracy for diagnosis of GORD. Symptom response to a 2 week course of 40 mg of esomeprazole does not add diagnostic precision.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Child; Esomeprazole; Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Sensitivity and Specificity; Single-Blind Method; Surveys and Questionnaires; Treatment Outcome

The aim of the study was to evaluate erosive esophagitis healing and symptom improvement with once-daily esomeprazole in children ages 12 to 36 months with endoscopically or histologically proven gastroesophageal reflux disease (GERD).. Data from children ages 12 to 36 months were included in a post-hoc analysis of an 8-week, multicenter, randomized, and double-blind by dose strata study of patients ages 1 to 11 years with endoscopically or histologically confirmed GERD. Children were randomized to receive esomeprazole 5 or 10 mg once daily. Patients underwent endoscopy and, if required, mucosal biopsy at baseline. Patients who had erosive esophagitis (graded using the Los Angeles classification system) at baseline underwent a follow-up endoscopy at final study visit to assess healing of erosive esophagitis. Investigators scored severity of GERD symptoms at baseline and every 2 weeks using the Physician Global Assessment.. Thirty-one of 109 primary study patients ages 12 to 36 months were included in the post hoc analysis. At baseline, 15 patients (48.4%) had erosive esophagitis, underwent follow-up endoscopy, and were healed after 8 weeks of esomeprazole treatment. Of the 19 patients with moderate-to-severe baseline Physician Global Assessment symptom scores, 84.2% had lower scores by the final visit. Following esomeprazole treatment, GERD symptoms were significantly improved from baseline to final visit (P ≤ 0.0018).. Esomeprazole 5 or 10 mg may be used to successfully treat erosive esophagitis and symptoms of GERD in children as young as 1 year. Moreover, although not yet validated in pediatric patients, the Los Angeles classification system was useful in grading erosive esophagitis in children ages 12 to 36 months.

Topics: Anti-Ulcer Agents; Child, Preschool; Double-Blind Method; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Infant; Male; Treatment Outcome

Proton pump inhibitors (PPIs) are effective in gastroesophageal reflux disease (GERD), but their cost effectiveness is unknown. This is usually determined by cost/quality-adjusted life year (QALY) gained, but whether PPI therapy improves QALYs has not been assessed in a randomized trial. The PPI acid suppression symptom (PASS) test is a five-item questionnaire that identifies patients with persistent acid-related symptoms. We evaluated whether a PASS test-based management strategy of changing GERD therapy to esomeprazole in those with continued symptoms on another PPI or H(2) receptor antagonist therapy would be cost effective. We expressed the data in terms of cost per quality-adjusted life months (QALM), as this was a 4-week trial.. This is a multicenter, cluster-randomized, open-label study in primary care physician centers across Canada. Primary care physician centers were randomized to intervention or control arms. Patients on acid-suppressing medication were identified from primary care records and asked to complete the PASS test. PASS test failures at baseline assessment continued current therapy in control practices or switched to esomeprazole 20 or 40 mg daily (the dose was at the clinician's discretion) for 4 weeks in intervention practices. A planned secondary end point was QALM gain, measured using the validated Euroqol (EQ-5D) completed at baseline and 4 weeks. Medication use was also assessed by questionnaire. Canadian unit generic costs were applied to all GERD drugs, except to esomeprazole and lansoprazole, wherein proprietary costs were used (all costs in Canadian $). Data were analyzed using bootstrap sampling.. A total of 1,564 patients were recruited from 134 intervention sites and 92 control sites. Data were evaluable for 808 intervention and 445 control patients. The mean (±standard deviation) QALM at 4 weeks in the intervention group was 0.885±0.164 compared with 0.814±0.179 in the control group, resulting in a mean 0.071 (95% CI=0.091-0.051) QALM gain (P<0.0001). Esomeprazole was cost effective for PASS test failures, with a mean cost of $763 (95% CI=456-1,414) per QALM gain.. Esomeprazole was associated with a statistically significant gain in QALMs and was cost effective in primary care patients with persistent acid-related symptoms identified by the PASS test.

Topics: Anti-Ulcer Agents; Canada; Cost-Benefit Analysis; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Primary Health Care; Quality-Adjusted Life Years; Surveys and Questionnaires; Treatment Outcome

In this pilot study, we attempted to determine the optimal dosage regimens of esomeprazole for treatment of GERD with minimal influence of the CYP2C19 polymorphism through a study of the pharmacokinetics and pharmacodynamics of esomeprazole given at 3 different dosage regimens with the same total daily dose.. Each of the 3 genotypes of CYP2C19, homozygous extensive metabolizers (homEMs), heterozygous EMS (hetEMs), and poor metabolizers (PMs) were recruited in this clinical trial. Subjects were given a placebo followed by the administration of esomeprazole, at a dose of 40 mg once daily (40QD), 20 mg twice daily (20TD), or 10 mg 4 times daily (10Q4D) for 7 days. Twenty-four-hour and nocturnal intragastric pH and plasma esomeprazole concentrations were all determined on day 7.. The pharmacokinetic parameters and dynamic characteristics differed among the 3 CYP2C19 genotype groups. With esomeprazole 40QD, gastric acid suppression was insufficient to achieve a therapeutic effect, while 20TD and 10Q4D were found to be effective in controlling both daytime and nocturnal gastric acidity for all 3 genotype groups.. It was confirmed that intragastric pH values and plasma esomeprazole concentrations potentially depended on the CYP2C19 genotype status for treatment with esomeprazole. Dosage regimens of divided doses of 20TD or 10Q4D esomeprazole yielded improved antisecretory effects with a minimal influence of CYP2C19 polymorphisms.

Topics: Adult; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C19; Down-Regulation; Drug Administration Schedule; Esomeprazole; Gastric Acid; Gastric Acidity Determination; Gastroesophageal Reflux; Gene Frequency; Heterozygote; Homozygote; Humans; Phenotype; Pilot Projects; Polymorphism, Genetic; Proton Pump Inhibitors; Taiwan; Treatment Outcome; Young Adult

A trial of empirical PPI therapy is usual practice for most patients with symptoms of gastro-oesophageal reflux disease (GERD) in primary care.. To determine if the 4-week efficacy of rabeprazole 20 mg for resolving heartburn and regurgitation symptoms is non-inferior to esomeprazole 40 mg or 20 mg.. In all, 1392 patients were randomized to rabeprazole 20 mg, esomeprazole 20 mg or 40 mg once daily. Patients, doctors and assessors were blinded. Symptom resolution data were collected on days 0-7 and day-28 using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index with a shortened version used on days 8-27.. Rabeprazole 20 mg was non-inferior to esomeprazole 40 mg for complete resolution of regurgitation and satisfactory resolution of heartburn and regurgitation. For complete heartburn resolution, the efficacy of rabeprazole 20 mg and esomeprazole 40 mg was statistically indistinguishable, although the non-inferiority test was inconclusive. Rabeprazole 20 mg was non-inferior to esomeprazole 20 mg for all outcomes.. In uninvestigated GERD patients, rabeprazole 20 mg was non-inferior to esomeprazole 40 mg for complete and satisfactory relief of regurgitation and satisfactory relief of heartburn, and not different for complete resolution of heartburn.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Heartburn; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Primary Health Care; Rabeprazole; Time Factors; Treatment Outcome; Young Adult

Alternative treatments are commonly used for various disorders and often taken on-demand. On-demand treatment of gastroesophageal reflux disease (GERD) with pharmaceutical products is an established, cost-effective strategy. Comparisons between alternative medicine and pharmaceutical products are rare. The aim of this trial was to compare on-demand treatment with a pectin-based, raft-forming, natural, anti-reflux agent (PRA) with that of esomeprazole 20 mg (Eso20) in patients with mild/moderate GERD.. Patients with mild/moderate GERD were randomised to a six weeks' on-demand treatment with PRA or Eso20 in a pragmatic, open, multicentre trial. Overall satisfaction with treatment, satisfactory relief on a weekly basis, reflux symptoms, and treatment preferences were noted.. Seventy-seven patients were included in the analyses. Eso20 was significantly superior to PRA for proportion of overall satisfied patients (92% and 58% respectively; p = 0.001), reduction of symptoms (mean symptom scores at the end 5.9 and 8.0 respectively; p = 0.019), proportion of weeks of satisfactory relief (89% and 62% respectively; p = 0.008) and proportion preferring continuation with the same treatment (85% and 42% respectively; p < 0.001). Older patients were more satisfied than younger, and patients preferring on-demand treatment had lower symptom scores at inclusion than those preferring regular treatment.. On-demand treatment with esomeprazole 20 mg was clearly superior to the pectin-based raft-forming agent. Most patients preferred on-demand treatment to regular treatment. Those preferring regular therapy had significantly more symptoms at inclusion.

Topics: Adult; Anti-Ulcer Agents; Bicarbonates; Complementary Therapies; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Magnesium; Male; Middle Aged; Patient Satisfaction; Pectins; Potassium Compounds

To clarify whether there is any difference in the symptom relief in patients with reflux esophagitis following the administration of four Proton pump inhibitors (PPIs).. Two hundred and seventy-four patients with erosive reflux esophagitis were randomized to receive 8 wk of 20 mg omeprazole (n = 68), 30 mg of lansoprazole (n = 69), 40 mg of pantoprazole (n = 69), 40 mg of esomeprazole (n = 68) once a day in the morning. Daily changes in heartburn and acid reflux symptoms in the first 7 d of administration were assessed using a six-point scale (0: none; 1: mild; 2: mild-moderate; 3: moderate; 4: moderate-severe; 5: severe).. The mean heartburn score in patients treated with esomeprazole more rapidly decreased than those receiving other PPI. Complete resolution of heartburn was also more rapid in patients treated with esomeprazole for 5 d compared with omeprazole (P = 0.0018, P = 0.0098, P = 0.0027, P = 0.0137, P = 0.0069, respectively), lansoprazole (P = 0.0020, P = 0.0046, P = 0.0037, P = 0.0016, P = 0.0076, respectively), and pantoprazole (P = 0.0006, P = 0.0005, P = 0.0009, P = 0.0031, P = 0.0119, respectively). There were no significant differences between the four groups in the rate of endoscopic healing of reflux esophagitis at week 8.. Esomeprazole may be more effective than omeprazole, lansoprazole, and pantoprazole for the rapid relief of heartburn symptoms and acid reflux symptoms in patients with reflux esophagitis.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Esomeprazole; Female; Gastroesophageal Reflux; Heartburn; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Pantoprazole; Patient Selection

Gastroesophageal reflux is common among patients with asthma but often causes mild or no symptoms. It is not known whether treatment of gastroesophageal reflux with proton-pump inhibitors in patients who have poorly controlled asthma without symptoms of gastroesophageal reflux can substantially improve asthma control.. In a parallel-group, double-blind trial, we randomly assigned 412 participants with inadequately controlled asthma, despite treatment with inhaled corticosteroids, and with minimal or no symptoms of gastroesophageal reflux to receive either 40 mg of esomeprazole twice a day or matching placebo. Participants were followed for 24 weeks with the use of daily asthma diaries, spirometry performed once every 4 weeks, and questionnaires that asked about asthma symptoms. We used ambulatory pH monitoring to ascertain the presence or absence of gastroesophageal reflux in the participants. The primary outcome was the rate of episodes of poor asthma control, as assessed on the basis of entries in asthma diaries.. Episodes of poor asthma control occurred with similar frequency in the placebo and esomeprazole groups (2.3 and 2.5 events per person-year, respectively; P=0.66). There was no treatment effect with respect to individual components of the episodes of poor asthma control or with respect to secondary outcomes, including pulmonary function, airway reactivity, asthma control, symptom scores, nocturnal awakening, or quality of life. The presence of gastroesophageal reflux, which was documented by pH monitoring in 40% of participants with minimal or no symptoms, did not identify a subgroup of patients that benefited from treatment with proton-pump inhibitors. There were fewer serious adverse events among patients receiving esomeprazole than among those receiving placebo (11 vs. 17).. Despite a high prevalence of asymptomatic gastroesophageal reflux among patients with poorly controlled asthma, treatment with proton-pump inhibitors does not improve asthma control. Asymptomatic gastroesophageal reflux is not a likely cause of poorly controlled asthma. (ClinicalTrials.gov number, NCT00069823.)

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Therapy, Combination; Esomeprazole; Female; Forced Expiratory Volume; Gastroesophageal Reflux; Humans; Male; Proton Pump Inhibitors; Regression Analysis; Treatment Failure

Rebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI). If RAHS induces acid-related symptoms, this might lead to PPI dependency and thus have important implications.. A randomized, double-blind, placebo-controlled trial with 120 healthy volunteers was conducted. Participants were randomized to 12 weeks of placebo or 8 weeks of esomeprazole 40 mg/d followed by 4 weeks with placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was filled out weekly. A score of >2 on 1 of the questions regarding heartburn, acid regurgitation, or dyspepsia was defined as a clinically relevant acid-related symptom.. There were no significant differences between groups in GSRS scores at baseline. GSRS scores for acid-related symptoms were significantly higher in the PPI group at week 10 (1.4 +/- 1.4 vs 1.2 +/- 0.9; P = .023), week 11 (1.4 +/- 1.4 vs 1.2 +/- 0.9; P = .009), and week 12 (1.3 +/- 1.2 vs 1.0 +/- 0.3; P = .001). Forty-four percent (26/59) of those randomized to PPI reported > or = 1 relevant, acid-related symptom in weeks 9-12 compared with 15% (9/59; P < .001) in the placebo group. The proportion reporting dyspepsia, heartburn, or acid regurgitation in the PPI group was 13 of 59 (22%) at week 10, 13 of 59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001).. PPI therapy for 8 weeks induces acid-related symptoms in healthy volunteers after withdrawal. This study indicates unrecognized aspects of PPI withdrawal and supports the hypothesis that RAHS has clinical implications.

Topics: Adolescent; Adult; Double-Blind Method; Drug Administration Schedule; Dyspepsia; Esomeprazole; Female; Gastric Acid; Gastric Mucosa; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Proton Pump Inhibitors; Reference Values; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult

To characterize the pharmacodynamics and systemic exposure of esomeprazole in 26 preterm infants and term neonates with symptoms of gastroesophageal reflux and pathologic acid exposure.. Enrolled patients received oral esomeprazole 0.5 mg/kg once daily for 7 days. Twenty-four-hour esophagogastric pH-impedance monitoring was performed at baseline and on day 7. Pharmacokinetic analysis was performed on day 7. Symptoms occurring during the baseline and day 7 studies were recorded on a symptom chart.. There were no significant differences from baseline to day 7 of therapy in the frequency of bolus reflux, consistency of bolus reflux (liquid, mixed, or gas), extent of bolus reflux, or bolus clearance time. Acid bolus reflux episodes were reduced on therapy (median 30 vs 8, P < .001), as was the reflux index (mean % time esophageal pH < 4, 15.7% vs 7.1%, P < .001). The estimated geometric mean of area under the plasma concentration time curve during the dosing interval and observed maximum plasma concentration was 2.5 micromol x h/L and 0.74 micromol/L, respectively. The number of gastroesophageal reflux symptoms recorded over 24 hours was lower on therapy (median 22 vs 12, P < .05).. In preterm infants and term neonates esomeprazole produces no change in bolus reflux characteristics despite significant acid suppression.

Topics: Administration, Oral; Anti-Ulcer Agents; Crying; Electric Impedance; Esomeprazole; Esophageal pH Monitoring; Female; Food; Gagging; Gastroesophageal Reflux; Humans; Infant, Newborn; Infant, Premature; Irritable Mood; Male; Vomiting

The primary objective was to assess gastroesophageal reflux disease (GERD) symptom resolution rates with esomeprazole by erosive esophagitis (EE) status, and the secondary objective was to evaluate potential predictors of the presence of EE and heartburn resolution.. Patients with GERD who have EE have higher reported symptom resolution rates than those with nonerosive reflux disease (NERD) when treated with proton pump inhibitors (PPIs).. This open-label multicenter study included adults with GERD symptoms. Patients were stratified by EE status after endoscopy and received once-daily esomeprazole 40 mg for 4 weeks. Questionnaires determined symptom response rates, and baseline predictors of EE or heartburn resolution were evaluated. Potential predictors, including years with GERD, history of EE, and time to relief with antacids, were examined.. Heartburn resolution rates at 4 weeks were higher for patients with EE than NERD (69% [124/179] vs. 48% [85/177]; p < 0.0001). Multivariate models had moderate predictive ability for EE (c-index, 0.76) and poor predictive ability (c-index, 0.57) for heartburn resolution. However, faster heartburn relief with antacid use, particularly within 15 min, was predictive of EE and heartburn resolution.. Patients with EE have higher heartburn resolution rates than patients with NERD after treatment, although recall bias may be possible. Fast relief with antacid use is predictive of EE and heartburn resolution with a PPI and suggests that a history of antacid relief may provide corroborative evidence to empiric PPI therapy in determining whether patients with heartburn have acid reflux disease. ClinicalTrials.Gov IDENTIFIER: NCT00242736.

Topics: Adult; Aged; Antacids; Anti-Ulcer Agents; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Models, Biological; Prognosis; Risk Factors; Young Adult

Combined pH-metry/multichannel intraluminal impedance (pH/MII) measurement enables to measure gastroesophageal reflux despite ongoing proton pump inhibitor therapy. The aim of our study was to evaluate the influence of an escalating medical anti-reflux therapy with 40 mg esomeprazole, 80 mg esomeprazole and 80 mg esomeprazole plus baclofen for the treatment of refractory pathological reflux as determined by pH/MII.. Symptomatic patients under 40 mg esomeprazole were screened by pH/MII. Patients with normal values in pH/MII were excluded; all others received 2 x 40 mg esomeprazole for another 4 weeks. Thereafter, the treatment effect was controlled by pH/MII. In the case of persistent pathological reflux, therapy was further escalated by adding baclofen and controlled after 3 months by pH/MII.. 45/138 (32.6%) patients showed pathological pH/MII despite ongoing therapy with 40 mg esomeprazole. In these, a significant reduction in liquid/mixed reflux events was observed after administering 2 x 40 mg (mean: 118.3 vs. mean: 66.6; p < 0.001), and pH/MII turned to normal in 32/45 (71.1%). Baclofen was additionally administered to 7/13 patients, which did not lead to a remarkable reduction in reflux events.. In patients with abnormal pH/MII and persistent symptoms under 40 mg esomeprazole, we observed a significant reduction in liquid/mixed reflux events after increasing proton pump inhibitor dose up to 80 mg esomeprazole. Further escalation of therapy with baclofen has shown inconclusive results.

Topics: Adult; Aged; Aged, 80 and over; Baclofen; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electric Impedance; Esomeprazole; Esophageal pH Monitoring; Esophageal Sphincter, Lower; Female; GABA Agonists; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Treatment Outcome; Young Adult

Dental erosion, the chemical dissolution of enamel without bacterial involvement, is a rarely reported manifestation of gastroesophageal reflux disease (GERD), as well as of recurrent vomiting and dietary habits. It leads to loss of tooth substance, hypersensitivity, functional impairment, and even tooth fracture. To date, dental erosions have been assessed using only very basic visual methods, and no evidence-based guidelines or studies exist regarding the prevention or treatment of GERD-related dental erosions.. In this randomized, double-blind study, we used optical coherence tomography (OCT) to quantify dental tissue demineralization and enamel loss before and after 3 weeks of acid-suppressive treatment with esomeprazole 20 mg b.i.d. or placebo in 30 patients presenting to the Berne University Dental Clinic with advanced dental erosions and abnormal acid exposure by 24-h esophageal pH manometry (defined as >4% of the 24-h period with pH<4). Enamel thickness, reflectivity, and absorbance as measures of demineralization were quantified by OCT before and after therapy at identical localizations on teeth with most severe visible erosions as well as several other predefined changes in teeth.. The mean+/-s.e.m. decrease of enamel thickness of all teeth before and after treatment at the site of maximum exposure was 7.2+/-0.16 black trianglem with esomeprazole and 15.25+/-0.17black trianglem with placebo (P=0.013), representing a loss of 0.3% and 0.8% of the total enamel thickness, respectively. The change in optical reflectivity to a depth of 25 black trianglem after treatment was-1.122 +/-0.769 dB with esomeprazole and +2.059+/-0.534 dB with placebo (P 0.012), with increased reflectivity signifying demineralization.. OCT non-invasively detected and quantified significantly diminished progression of dental tissue demineralization and enamel loss after only 3 weeks of treatment with esomeprazole 20 mg b.i.d. vs. placebo. This suggests that esomeprazole may be useful in counteracting progression of GERD-related dental erosions. Further validation of preventative treatment regimens using this sensitive detection method is required, including longer follow-up and correlation with quantitative reflux measures.

Topics: Adult; Anti-Ulcer Agents; Dental Enamel; Double-Blind Method; Esomeprazole; Esophageal pH Monitoring; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Male; Pilot Projects; Probability; Reference Values; Risk Assessment; Severity of Illness Index; Tomography, Optical Coherence; Tooth Erosion; Treatment Outcome

Silent gastroesophageal reflux (GER) is common in patients with asthma, but it is unclear whether GER is associated with worse asthma symptoms or reduced lung function.. To determine in patients with poorly controlled asthma, whether proximal or distal esophageal reflux is associated with asthma severity, symptoms, physiology, or functional status.. Baseline asthma characteristics were measured in patients with asthma enrolled in a multicenter trial assessing the effectiveness of esomeprazole on asthma control. All participants underwent 24-hour esophageal pH probe monitoring. Lung function, methacholine responsiveness, asthma symptoms, and quality-of-life scores were compared in subjects with and without GER.. Of 304 participants with probe recordings, 53% had reflux. Of 242 participants with recordings of proximal pH, 38% had proximal reflux. There was no difference in need for short-acting bronchodilators, nocturnal awakenings, dose of inhaled corticosteroid, use of long-acting beta-agonists, lung function, or methacholine reactivity between individuals with and without proximal or distal GER. Participants with GER reported more use of oral corticosteroids and had worse asthma quality of life and subjects with proximal GER had significantly worse asthma quality of life and health-related quality of life compared with participants without GER.. Asymptomatic GER is not associated with distinguishing asthma symptoms or lower lung function in individuals with suboptimal asthma control who are using inhaled corticosteroids. Patients with proximal reflux report significantly worse asthma and health-related quality of life despite lack of physiologic impairment or increase in asthma symptoms. Clinical trial registered with www.clinicaltrials.gov (NCT00069823).

Topics: Adrenal Cortex Hormones; Adult; Anti-Ulcer Agents; Asthma; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Lung; Male; Monitoring, Physiologic; Quality of Life; Severity of Illness Index

Although gastroesophageal reflux disease (GERD) is common in adolescents, the burden of GERD on health-related quality of life (HRQOL) in adolescents has not been previously evaluated. Therefore, the objective of the study was to examine the effect of GERD on HRQOL in adolescents.. This international, 31-site, 8-week safety study randomized adolescents, aged 12 to 17 years inclusive, with GERD to receive esomeprazole 20 or 40 mg once daily. The Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD), previously validated in adults, consists of 25 questions grouped into 5 domains: emotional distress, sleep disturbance, food/drink problems, physical/social functioning, and vitality. The QOLRAD was administered at the baseline and week-8 (final) visits.. Of the 149 patients randomized, 134 completed the QOLRAD at baseline and final visits and were eligible for analysis of their HRQOL data. Baseline QOLRAD scores indicated GERD had a negative effect on the HRQOL of these adolescents, especially in the domains of vitality and emotional distress, and problems with food/drink. At the final visit, mean scores for all 5 QOLRAD domains improved significantly (P < .0001); change of scores (ie, delta) for all domains met or exceeded the adult QOLRAD minimal clinically significant difference standard of 0.5 units.. GERD had a negative effect on QOL in adolescents. After esomeprazole treatment, statistically and clinically significant improvements occurred in all domains of the QOLRAD for these adolescents.. D9614C00098; ClinicalTrials.gov Identifier NCT00241501.

Topics: Administration, Oral; Adolescent; Canada; Child; Dose-Response Relationship, Drug; Double-Blind Method; Enzyme Inhibitors; Esomeprazole; Female; Follow-Up Studies; France; Gastroesophageal Reflux; Humans; Italy; Male; Quality of Life; Surveys and Questionnaires; Treatment Outcome; United States

The long-term management of gastroesophageal reflux in patients with Barrett's esophagus (BE) is not well supported by an evidence-based consensus. We compare treatment outcome in patients with and without BE submitted to standardized laparoscopic antireflux surgery (LARS) or esomeprazole treatment.. In the Long-Term Usage of Acid Suppression Versus Antireflux Surgery trial (a European multicenter randomized study), LARS was compared with dose-adjusted esomeprazole (20-40 mg daily). Operative difficulty, complications, symptom outcomes [Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD)], and treatment failure at 3 years and pH testing (after 6 months) are reported.. Of 554 patients with gastroesophageal reflux disease, 60 had BE-28 randomized to esomeprazole and 32 to LARS. Very few BE patients on either treatment strategy (four of 60) experienced treatment failure during the 3-year follow-up. Esophageal pH in BE patients was significantly better controlled after surgical treatment than after esomeprazole (p = 0.002), although mean GSRS and QOLRAD scores were similar for the two therapies at baseline and at 3 years. Although operative difficulty was slightly greater in patients with BE than those without, there was no difference in postoperative complications or level of symptomatic reflux control.. In a well-controlled surgical environment, the success of LARS is similar in patients with or without BE and matches optimized medical therapy.

Topics: Anti-Ulcer Agents; Barrett Esophagus; Esomeprazole; Female; Fundoplication; Gastroesophageal Reflux; Humans; Laparoscopy; Male; Middle Aged

To determine the efficacy of proton pump inhibitor (PPI) therapy with esomeprazole on symptoms and signs associated with laryngopharyngeal reflux (LPR).. Prospective, double-blind, randomized, placebo-controlled study. Sixty-two patients with a reflux finding score (RFS)>7 and a reflux symptom index (RSI)>13 were enrolled and received either esomeprazole 20 mg twice daily or placebo for three months. RSI and RFS were assessed at baseline, after six weeks, and after three months.. Reductions of total RSI and RFS as well as of several subscores were significantly higher in the treatment group compared to placebo after three months (P<0.05 each). The difference between study groups was most pronounced for posterior commissure hypertrophy (P<0.01).. In the treatment of LPR-related symptoms a high placebo effect can be observed. However, compared to control, twice-daily PPI treatment for three months demonstrated a significantly greater improvement in laryngeal appearance and LPR symptoms.

Topics: Adult; Aged; Anti-Ulcer Agents; Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Hypertrophy; Hypopharynx; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors

Patients with gastroesophageal reflux disease (GERD) are advised to avoid alcoholic beverages since alcohol consumption induces gastroesophageal reflux in healthy volunteers and increases it in patients with GERD. Proton-pump inhibitors (PPIs) are frequently administered for reflux symptoms but their effect on gastroesophageal reflux after alcohol consumption has not yet been fully studied. The aim of the present study was therefore to investigate the effect of esomeprazole, an S-enantiomer of omeprazole, on gastroesophageal reflux after beer consumption.. In this placebo-controlled, double-blind, crossover study, 16 healthy male volunteers received 20 mg esomeprazole daily for one week. On day 7, in an acute experiment, the subjects then consumed 500 ml beer within 5 min. Subsequently, gastroesophageal reflux was monitored by pH-metry over a period of 3 h. In addition, gastric emptying was measured by ultrasonography and blood concentrations of ethanol, cholecystokinin and gastrin were determined.. Gastroesophageal reflux was significantly (p=0.001) reduced by 93% after treatment with esomeprazole (0.2%, median percentage of time pH<4) as compared to placebo (2.6%), but gastric emptying, blood ethanol and cholecystokinin concentrations were not significantly different after esomeprazole treatment. Plasma gastrin levels were significantly (p=0.0003) higher after esomeprazole (98.6+/-19.7 pg/ml) than after placebo (22.7+/-3.8 pg/ml) before beer consumption. However, there was no difference in the increase in plasma gastrin after beer consumption between the esomeprazole treatment and placebo.. Esomeprazole significantly reduces gastroesophageal reflux after beer consumption in healthy volunteers. Gastric emptying of beer is not prolonged after treatment with esomeprazole, although compared with placebo, this PPI induced significantly higher plasma gastrin concentrations. Moderate alcohol consumption does not worsen gastroesophageal reflux when a PPI is administered.

Topics: Adult; Beer; Double-Blind Method; Esomeprazole; Esophageal pH Monitoring; Gastroesophageal Reflux; Humans; Male; Proton Pump Inhibitors; Treatment Outcome

To assess the values of endoscopy, 24-hour esophageal pH monitoring, symptom index, 24-hour esophageal bile monitoring, and proton pump inhibitor (PPI) trail in the diagnosis of gastroesophageal reflux disease (GERD)-related noncardiac chest pain (NCCP).. 27 NCCP patients, selected from a consecutive sample of 255 patients who had received coronary angiography owing to chest pain, underwent upper endoscopy, and 24-hour esophageal pH and bile monitoring, then they took esomeprazole 20 mg orally twice daily for 14 days. Symptom score (SI) was used to measure the severity and frequency of chest pain before and after treatment. The patients also underwent an initial questionnaire survey including the general personal data and symptom characters, reflux diagnostic questionnaire (RDQ), self-rating anxiety scale (SAS) survey, and self-rating depression scale (SDS) survey.. If only based on erosive esophagitis and/or abnormal 24-hour esophageal pH monitoring, 9 of the 27 patients (33%) were classified as GERD-related NCCP. Otherwise, 74% (20 of the 27 patients were classified as GERD-related NCCP based on erosive esophagitis and/or abnormal 24-hour esophageal pH monitoring, or positive SI or abnormal bile monitoring. 15 of the 20 GERD patients (75%) had a significant symptom improvement on PPI compared with 14% (1/7) of non-GERD patients (P = 0. 009). The calculated sensitivity and specificity of the PPI trail was 75% and 86% respectively. The typical reflux symptoms presented more frequently among GERD patients than non-GERD patients [65% (13/20) vs 29% (2/7), P = 0.185]. There was no significant RDQ score difference between the 2 groups (10 +/- 4 vs 8 +/- 4, P = 0.411). The sensitivity and specificity of RDQ to GERD-related NCCP were 35% and 86% respectively. The SAS scores of GERD and non-GERD-related NCCP patients were both significantly higher than that of the normal controls (P = 0.008 and P = 0.011), while the SDS scores of the GERD and non-GERD-related NCCP patients were both similar to that of the normal controls (P = 0.090 and P = 0.113).. Combination of endoscopy, 24-hour esophageal pH monitoring, SI, and 24-hour esophageal bile monitoring helped to improve the diagnosis of GERD-related NCCP. PPI trail is the first clinical diagnostic tool in the evaluation of GERD-related NCCP.

Topics: Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Chest Pain; Coronary Angiography; Esomeprazole; Esophagus; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Monitoring, Physiologic; Pain Measurement; Reproducibility of Results; Sensitivity and Specificity; Surveys and Questionnaires

Some patients with gastro-oesophageal reflux disease (GORD) remain symptomatic despite proton pump inhibitor (PPI) treatment. There is a need to determine the most appropriate management of these patients.. To assess the effectiveness of esomeprazole 40 mg in GORD symptoms persisting in patients receiving a full daily dose PPI.. In this multi-centre open label study patients who had received full daily dose PPI for 8 weeks, but were still experiencing persistent GORD symptoms, were treated with esomeprazole 40 mg for 8 weeks (n = 99). The primary outcome variable was the change in the frequency of heartburn. Patient-reported outcomes were also assessed using the Reflux Disease Questionnaire (RDQ) and the GORD Impact Scale (GIS).. The mean frequency of heartburn was reduced by 78% from 4.4 days a week to 1 day a week at the end of the 8-week treatment period (p < 0.0001). Other GORD symptoms were also significantly reduced following of treatment with esomeprazole (all p < 0.0001). All RDQ dimensions and the level of symptom control as measured by the GIS also showed significant improvement at 8 weeks.. In patients with persistent GORD symptoms despite full dose daily PPI therapy, esomeprazole 40 mg significantly improved the frequency and severity of all GORD symptoms.

Topics: Anti-Ulcer Agents; Chronic Disease; Esomeprazole; Female; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Proton Pump Inhibitors; Secondary Prevention; Treatment Outcome

AZD0865 is a gastric acid-suppressing agent that has a rapid onset of action and long duration of effect. This double-blind, randomized, multicenter study investigated the efficacy and safety of AZD0865 in the treatment of patients with nonerosive reflux disease (NERD).. Patients with troublesome heartburn for at least 6 months and no evidence of erosions at endoscopy were randomized to receive AZD0865 (25, 50, or 75 mg/day) or esomeprazole 20 mg/day, for 4 wk. Throughout the treatment period, patients reported the presence and intensity of heartburn and other NERD symptoms twice daily using an electronic diary. Twenty-four-hour ambulatory intraesophageal/intragastric pH monitoring was performed in a subset of patients on day 14.. A total of 1,469 patients were randomized. The median time to sustained absence of heartburn (for 7 consecutive days) was approximately 12 days for all treatment groups and did not differ significantly for any of the AZD0865 doses or compared with esomeprazole. There were no significant differences among treatment groups in the cumulative incidence of sustained absence of heartburn during 4 wk treatment (i.e., 65-70%). The percentage of time for which intragastric pH was greater than 4 was significantly greater for AZD0865 75 mg/day compared with esomeprazole 20 mg (75% vs 60%, P < 0.05). AZD0865 was generally well tolerated although reversible elevations of liver transaminases occurred in some patients receiving the agent.. AZD0865 did not provide clinical benefit over esomeprazole 20 mg in the management of patients with NERD.

Topics: Administration, Oral; Adolescent; Adult; Aged; Dose-Response Relationship, Drug; Double-Blind Method; Endoscopy, Gastrointestinal; Enzyme Inhibitors; Esomeprazole; Esophagus; Female; Follow-Up Studies; Gastric Acidity Determination; Gastroesophageal Reflux; Heartburn; Humans; Hydrogen-Ion Concentration; Imidazoles; Male; Middle Aged; Pyridines; Retrospective Studies; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Whether patients with typical gastroesophageal reflux disease (GERD) symptoms and without alarm features should be treated empirically or undergo endoscopy first is a debated issue. In this study, our aim was to assess the efficacy, and to compare the direct costs and impact on health-related quality of life (HRQL), of two treatment strategies (empirical vs endoscopy-oriented treatment) in a large population of patients with GERD.. In total, 612 patients were randomized to either empirical treatment with esomeprazole 40 mg once daily (od) (group 1, N = 309) or endoscopy and treatment according to endoscopic findings (group 2, N = 303, esomeprazole 40 mg od in patients with reflux esophagitis and esomeprazole 20 mg od in patients without esophagitis) for 4 wk, followed by esomeprazole 20 mg od maintenance treatment in both groups. Direct costs and HRQL were analyzed in both treatment arms.. At the end of the acute treatment phase (week 4), 267 patients in group 1 (86.4%) and 265 patients in group 2 (87.5%) were considered responders to treatment (intention-to-treat analysis, P= 0.878). Empirical treatment proved to be cost-effective by saving 38.72 euros per treated patient. At the end of the maintenance phase (week 24), a similar proportion of patients responded to treatment in the two groups (71.8%vs 68.3%, P= 0.389). HRQL improved from baseline to week 24 in both groups (difference between study groups not significant).. In patients with GERD, empirical treatment with esomeprazole proved to be cost-effective compared with endoscopy-oriented treatment, and did not negatively affect patient HRQL. These results should be taken into account in the management of GERD patients in clinical practice.

Topics: Adult; Anti-Ulcer Agents; Costs and Cost Analysis; Esomeprazole; Esophagoscopy; Female; Gastroesophageal Reflux; Gastroscopy; Humans; Male; Quality of Life

AGN 201904-Z is a new, slowly absorbed, acid-stable pro-proton pump inhibitor (pro-PPI) rapidly converted to omeprazole in the systemic circulation giving a prolonged residence time.. To investigate pharmacodynamics and pharmacokinetics of AGN 201904-Z compared to esomeprazole.. A randomized, open-label, parallel group, investigator-blinded intragastric pH study was conducted in 24 healthy Helicobacter pylori negative male volunteers. AGN 201904-Z enteric-coated capsules (600 mg/day) or esomeprazole delayed-release tablets (40 mg/day) were administered for 5 days. Twenty-four-hour intragastric pH recordings were acquired at baseline, days 1, 3 and 5 with blood levels of omeprazole, AGN 201904-Z and gastrin.. On day 1, median nocturnal pH and proportion of nocturnal time with pH >or=4 and 24-h and nocturnal time pH >or=5 were significantly higher with AGN 201904-Z than esomeprazole. At day 5, 24-h and median nocturnal pH were significantly higher for AGN 201904-Z than esomeprazole (P < 0.0001). There was also a marked reduction in periods of nocturnal pH <4.0. Area under curve of the AGN 201904-Z active metabolite (omeprazole) in the blood was twice that of esomeprazole at day 5.. AGN 201904-Z produced a significantly greater and more prolonged acid suppression than esomeprazole, and nocturnal acid suppression was more prolonged over all 5 days. AGN 201904-Z should provide true once-a-day treatment and better clinical efficacy than current PPIs.

Topics: Adult; Anti-Ulcer Agents; Esomeprazole; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Male; Omeprazole; Proton Pump Inhibitors; Treatment Outcome

With the introduction of laparoscopic antireflux surgery (LARS) for gastro-oesophageal reflux disease (GORD) along with the increasing efficacy of modern medical treatment, a direct comparison is warranted. The 3-year interim results of a randomised study comparing both the efficacy and safety of LARS and esomeprazole (ESO) are reported.. LOTUS is an open, parallel-group multicentre, randomised and controlled trial conducted in dedicated centres in 11 European countries. LARS was completed according to a standardised protocol, comprising a total fundoplication and a crural repair. Medical treatment comprised ESO 20 mg once daily, which could be increased stepwise to 40 mg once daily and then 20 mg twice daily in the case of incomplete GORD control. The primary outcome variable was time to treatment failure (Kaplan-Meier analysis). Treatment failure was defined on the basis of symptomatic relapse requiring treatment beyond that stated in the protocol.. 554 patients were randomised, of whom 288 were allocated to LARS and 266 to ESO. The two study arms were well matched. The proportions of patients who remained in remission after 3 years were similar for the two therapies: 90% of surgical patients compared with 93% medically treated for the intention to treat population, p = 0.25 (90% vs 95% per protocol). No major unexpected postoperative complications were experienced and ESO was well tolerated. However, postfundoplication complaints remain a problem after LARS.. Over the first 3 years of this long-term study, both laparoscopic total fundoplication and continuous ESO treatment were similarly effective and well-tolerated therapeutic strategies for providing effective control of GORD.

Topics: Adult; Anti-Ulcer Agents; Chronic Disease; Esomeprazole; Female; Fundoplication; Gastroesophageal Reflux; Humans; Laparoscopy; Male; Middle Aged; Quality of Life; Severity of Illness Index; Treatment Outcome

In patients with gastro-oesophageal reflux disease (GORD), dose escalation or drug switching may be considered in those with symptoms that persist despite standard-dose proton pump inhibitor (PPI) therapy. This study set out to assess whether increasing the dosage of oral esomeprazole and pantoprazole improves acid control in GORD patients, and to compare the pharmacodynamic efficacy of esomeprazole and pantoprazole administered at different dosages.. This was an open-label, randomized, six-way crossover study that included Helicobacter pylori-negative GORD patients (aged 20-60 years) with <30% of time with intragastric pH>4. Patients were treated with oral once-daily esomeprazole 20 mg, 40 mg and 80 mg, and pantoprazole 20 mg, 40 mg and 80 mg, for 5 days. The main outcome measures were time with intragastric pH>4 over 24 hours, median pH over 24 hours and area under the hydrogen ion versus time curve on day 5 for each treatment period.. Dose escalation with both PPIs improved acid control. The proportion of time with intragastric pH>4 (day 5) was 46.7% with esomeprazole 20 mg/day, 58.6% with esomeprazole 40 mg/day, and 65.8% with esomeprazole 80 mg/day; the corresponding percentages with pantoprazole were 28.6%, 36.9% and 44.9%, respectively. On a milligram-per-milligram basis, esomeprazole provided greater acid control than pantoprazole (p<0.001).. Dose escalation with oral esomeprazole and pantoprazole improves acid control in patients with GORD, although esomeprazole provides significantly greater acid control on a milligram-per-milligram basis.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Cross-Over Studies; Dose-Response Relationship, Drug; Esomeprazole; Female; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pantoprazole

To evaluate safety, tolerability, and symptom improvement with once-daily esomeprazole in children with endoscopically proven gastroesophageal reflux disease (GERD).. In this 8-week, multicenter, randomized, uncontrolled, double-blind study, children ages 1 to 11 years were stratified by weight to receive esomeprazole 5 or 10 mg (children <20 kg) or 10 or 20 mg (children >or=20 kg) once daily. Safety and tolerability was assessed by evaluating adverse events (AEs; both treatment- and non-treatment-related AEs) and changes from baseline in medical history, physical examinations, and clinical laboratory tests. Investigators scored symptom severity every 2 weeks using the Physician's Global Assessment (PGA). Patients' parents rated GERD symptoms of heartburn, acid regurgitation, and epigastric pain (none to severe, 0-3) at baseline (based on past 72 hours) and daily (from past 24 hours).. Of 109 patients randomized, 108 had safety data. AEs were experienced by 68.0% and 65.2% of children <20 kg receiving esomeprazole 5 and 10 mg, respectively, and 83.9% and 82.8% of children >or=20 kg receiving esomeprazole 10 and 20 mg, respectively, regardless of causality. Overall, only 9.3% of patients reported 13 treatment-related AEs; the most common were diarrhea (2.8% [3/108]), headache (1.9% [2/108]), and somnolence (1.9% [2/108]). Vomiting, a serious AE in 2 patients, was not judged by the investigator to be related to treatment. At the final visit, PGA scores improved significantly from baseline (P < 0.001). Of 58 patients with moderate to severe baseline PGA symptom scores, 91.4% had lower scores by the final visit. GERD symptom scores were significantly improved from baseline to the final week of the study in all of the treatment groups (P < 0.01). In children ages 1 to 11 years with endoscopically proven GERD, esomeprazole (at daily doses of 5, 10, or 20 mg) was generally well tolerated. The frequency and severity of GERD-related symptoms were significantly reduced during the active treatment period.

Topics: Child; Child, Preschool; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Enzyme Inhibitors; Esomeprazole; Female; Gastroesophageal Reflux; Headache; Humans; Infant; Male; Severity of Illness Index; Treatment Outcome

To examine the effect of esomeprazole in a fixed time setting on gastric content volume, gastric acidity, gastric barrier pressure, and reflux propensity.. Randomized, controlled, double-blind trial.. 21 healthy, ASA I physical status volunteers.. Esomeprazole was given 12 hours and one hour before investigation. Before the study, a multichannel intraluminal impedance catheter, pH monitoring data logger (PHmetry) catheter, and an intragastric-esophageal manometry catheter were placed nasally after topical anesthesia.. Gastric acidity and gastric content volume were determined by PHmetry after aspiration of gastric contents over a nasogastric tube. Gastroesophageal reflux and intragastric-esophageal barrier pressure were investigated by multichannel intraluminal impedance measurement, PHmetry, and intragastric-esophageal manometry.. The pH of gastric contents was significantly (P < 0.001) higher after esomeprazole (mean [25th-75th percentile], 4.2 [3.9-4.8] vs 2.0 [1.9-2.7]), and gastric content volume was significantly (P < 0.001) lower (5.0 mL [3.0-12.0] vs 15 mL [10.0-25.0]) in comparison to placebo. No significant difference between esomeprazole and placebo was found with respect to number of refluxes per person, duration of reflux, or barrier pressure.. Esomeprazole in a fixed time setting can markedly increase the pH of gastric contents and decrease gastric content volume, but has no influence on the frequency, duration of refluxes, or gastroesophageal barrier pressure.

Topics: Adult; Anti-Ulcer Agents; Double-Blind Method; Electric Impedance; Esomeprazole; Female; Gastric Acidity Determination; Gastroesophageal Reflux; Gastrointestinal Contents; Humans; Hydrogen-Ion Concentration; Male; Manometry; Pressure

Gastro-oesophageal reflux disease (GERD) patients on proton pump inhibitors before breakfast or dinner have acid recovery at night. Bedtime immediate-release omeprazole (IR-OME) demonstrated better control of nocturnal pH than pantoprazole before dinner.. To compare repeated once daily bedtime dosing of IR-OME, lansoprazole and esomeprazole on nocturnal gastric acidity.. Open-label, randomized, crossover study enrolling 54 patients with nocturnal GERD symptoms comparing IR-OME, lansoprazole and esomeprazole at steady state for nocturnal acid breakthrough (NAB), percentage of time with gastric pH > 4 and median gastric pH.. Onset of nocturnal acid control with IR-OME was rapid. During the first half of the night, percentage of time with gastric pH > 4 and median gastric pH were significantly higher after IR-OME compared to esomeprazole or lansoprazole (P < 0.001, both comparisons). Over the 8-h night-time period, acid control with IR-OME was significantly better than lansoprazole (P < 0.001), and comparable to esomeprazole. IR-OME reduced NAB compared with esomeprazole and lansoprazole (61% vs. 92% and 92%; P < 0.001, both comparisons).. Bedtime IR-OME provided more rapid control of night-time gastric pH and decreased NAB compared with esomeprazole and lansoprazole. Nocturnal acid control with IR-OME was superior to lansoprazole and comparable to esomeprazole. Bedtime dosing with IR-OME may be effective for patients with night-time heartburn.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adult; Aged; Antacids; Anti-Ulcer Agents; Cross-Over Studies; Drug Administration Schedule; Esomeprazole; Female; Gastric Acid; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Treatment Outcome

During sleep, individuals are uniquely vulnerable to acid reflux. Acid reflux during sleep has been studied by a number of investigators, but non-acid reflux is largely unexplored.. In this study, 15 individuals with significant subjective complaints of heartburn were treated with esomeprazole, 40 mg bid, and with placebo, in random order, for 1 week each. After 1 week of treatment, participants underwent combined impedence/pH monitoring and polysomnography. In both drug and placebo conditions, these procedures were done after participants consumed a meal designed to increase the likelihood of reflux events.. Total reflux events and acid reflux events were significantly decreased with proton-pump inhibitor (PPI) treatment as compared to placebo. Nonacid reflux events were more common with PPI treatment as compared to placebo, but this result was not statistically significant. The ratio of non-acidic to acidic events was significantly greater with PPI treatment, however. Similar results were found for reflux events that occurred only during sleep. Proximal migration of acidic vs non-acidic reflux events was found to be similar. There was no difference in sleep architecture between placebo and drug conditions.. PPI treatment reduced overall reflux events, but non-acidic reflux events were relatively more likely to occur with PPI treatment. The occurrence of these non-acidic reflux events on PPI might conceivably explain why some individuals continue to have symptoms after PPI treatment.

Topics: Anti-Ulcer Agents; Drug Administration Schedule; Electric Impedance; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Polysomnography; Proton Pump Inhibitors; Sleep; Treatment Outcome

To compare the efficacy and tolerability of pantoprazole 20 mg once daily with that of esomeprazole 20 mg once daily for 6 months as maintenance therapy in patients with previously healed gastroesophageal reflux disease.. In an initial open-label acute phase, outpatients with endoscopically confirmed gastroesophageal reflux disease (Los Angeles grades A-D) received pantoprazole 40 mg once daily for 4 or 8 weeks. Those healed (defined as the absence of esophagitis, and 'no' or 'mild' heartburn and acid regurgitation) were randomized in the double-blind manner for maintenance therapy with pantoprazole 20 mg once daily or esomeprazole 20 mg once daily for 6 months.. In the acute healing phase, 1452 patients were recruited to receive pantoprazole 40 mg once daily. Healing success was 91% (intent-to-treat analysis). A total of 1303 patients entered the maintenance phase of the study. Pantoprazole 20 mg once daily and esomeprazole 20 mg once daily were equally effective at maintaining patients in remission; 84 and 85% of pantoprazole and esomeprazole recipients remained in combined endoscopic and symptomatic remission at 6 months (intent-to-treat analysis). The confidence interval of the difference was (-5.7; +infinity), showing that pantoprazole is as effective as esomeprazole with a noninferiority margin of 5.8%. Combined endoscopic and symptomatic remission was independent of Helicobacter pylori status. Both treatments were well tolerated and safe.. Treatment with pantoprazole 20 mg once daily or esomeprazole 20 mg once daily provides similarly effective and well-tolerated maintenance of previously healed gastroesophageal reflux disease irrespective of baseline H. pylori status.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Double-Blind Method; Drug Administration Schedule; Esomeprazole; Female; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pantoprazole; Remission Induction; Secondary Prevention; Treatment Outcome

To assess the relationship between the percentage of time intragastric pH >4.0 and healing of erosive oesophagitis.. In this proof-of-concept study, adults with endoscopically verified Los Angeles grade C or grade D erosive oesophagitis were randomly assigned to oral esomeprazole 10 or 40 mg once daily for 4 weeks. On day 5, patients underwent 24-h pH monitoring. At 4 weeks, erosive oesophagitis healing status was endoscopically assessed. Investigators scored gastro-oesophageal reflux disease symptoms on a 4-point scale [none to severe (0-3)] before and 4 weeks after treatment. The percentage of time intragastric pH was >4.0 and healing status were correlated and tested for significance using a Spearman rank correlation (r).. 103 patients had evaluable data (mean age, 48.7 years; 65% men). Mean percentages of time with intragastric pH >4.0 on day 5 in patients with healed and unhealed erosive oesophagitis were 61% and 42%, respectively (P = 0.0002), indicating that erosive oesophagitis healing rates were positively related to the percentage of time intragastric pH was >4.0. Greater intragastric acid control correlated with lower final daytime and night-time heartburn and acid regurgitation symptom scores (r = -0.029, -0.029 and -0.021; P = 0.003, 0.003 and 0.032, respectively).. A positive relationship between intragastric acid control and erosive oesophagitis healing was demonstrated.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Double-Blind Method; Esomeprazole; Esophagitis, Peptic; Female; Gastric Acid; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Male; Middle Aged

To evaluate the asthma outcome of treatment with ranitidine or esomeprazole plus metoclopramide in older children with moderate-persistent asthma and gastroesophageal reflux disease (GERD).. The study patients included 44 patients with asthma and GERD who had received 1 year of treatment with a proton pump inhibitor/prokinetic combination and had shown significant clinical improvement in asthma symptoms and no exacerbations for more than 3 months. For further treatment, 30 of the 44 patients continued treatment with esomeprazole/metoclopramide (group A), and 14 switched to ranitidine (group B). Nine patients with GERD and asthma who had previously undergone fundoplication were used as control individuals (group C). All patients were followed up closely for exacerbation of asthma symptoms and treated according to a standardized protocol.. During the 6-month follow-up, group B patients experienced significantly more exacerbations per patient (2.2) than did those in group A (0.33) or group C (0.77) (P < 0.05).. Fundoplication or continued treatment with esomeprazole and metoclopramide is associated with significantly fewer exacerbations of asthma symptoms in children with moderate-persistent asthma and concomitant GERD in comparison with treatment with ranitidine.

Topics: Adolescent; Anti-Ulcer Agents; Antiemetics; Asthma; Child; Comorbidity; Enzyme Inhibitors; Esomeprazole; Female; Fundoplication; Gastroesophageal Reflux; Humans; Male; Metoclopramide; Proton Pump Inhibitors; Ranitidine; Treatment Outcome

To determine the level of acid control and the dose-response relationships achieved with esomeprazole and lansoprazole. These data are relevant in helping clinicians to decide on whether to increase a proton-pump inhibitor dose, or whether to switch to an alterative drug for increased acid control.. In an open-label, single-centre, randomized, six-way crossover study, 40 healthy subjects received esomeprazole 20, 40 and 80 mg, and lansoprazole 15, 30 and 60 mg once daily for 5 days. The mean time with intragastric pH >4 and mean 24-h median intragastric pH on day 5 were analyzed using a mixed-model ANOVA. Post-hoc analyses were completed for 0-12-h (daytime) and 12-24-h (night-time) post-dose intervals.. Increasing the dose of esomeprazole from 20 mg to 40 mg resulted in significantly improved acid control over 0-12, 12-24 and 0-24 h post-dose (p<0.001), but no significant improvement in acid control for either period was seen when further increasing the dose to 80 mg. Increasing the dose of lansoprazole from 15 mg to 30 mg or from 30 mg to 60 mg significantly improved acid control over 0-12 and 0-24 h (p<0.01) but not over 12-24 h. With the exception of the esomeprazole 20 mg versus lansoprazole 30 mg comparisons, and the esomeprazole 20 mg versus lansoprazole 15 mg during 12-24 h post-dose comparison, esomeprazole provided significantly greater acid control than lansoprazole at each dose level over 0-12, 12-24 and 0-24 h (p<0.05). Mean 24-h median intragastric pH was higher following esomeprazole dosing compared with lansoprazole at each dose level.. For low-, standard- and double-dose comparisons, esomeprazole achieved greater elevation of gastric pH and better acid control in more subjects than lansoprazole. Use of esomeprazole may therefore reduce the need for dose adaptations or drug switching.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Circadian Rhythm; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enzyme Inhibitors; Esomeprazole; Female; Follow-Up Studies; Gastric Acid; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Treatment Outcome

The most effective current treatment option for patients suffering from laryngopharyngeal reflux (LPR) is the use of proton pump inhibitors (PPIs). Compared to other PPIs, esomeprazole seems to provide best 24-h control of intragastric acid. However, some patients remain resistant to medical acid suppression with PPIs. The aim of this investigation was to identify the number of non-responders among patients suffering from LPR being treated by esomeprazole 40 mg once daily (officially approved maximum dosage).. Between June 2004 and January 2006, 27 patients suffering from LPR diagnosed by dual-probe pH monitoring were treated with esomeprazole 40 mg once daily. After 13-54 days (mean 28 days) while still under PPI-treatment, the 24-h pH-study was repeated in order to control the effectiveness of therapy. Patients with at least a reduction of the reflux area index (RAI) compared to the result before treatment were categorized as responders. Furthermore, the number of patients with a measurable reduction of proximal reflux episodes under PPI-treatment was quantified.. Repeated pH monitoring during PPI therapy revealed a reduction of the RAI in 22 of 27 patients. Five patients, however, showed a higher RAI despite medical treatment (19%). In 13 patients (48%), treatment with 40 mg esomeprazole once daily reduced the RAI to a normal value (<6.3). In 18 of 27 patients, the number of proximal reflux episodes has decreased (67%).. In a number of patients suffering from LPR, treatment with esomeprazole 40 mg once daily did not provide any measurable proximal acid reduction. Repeated pH monitoring during treatment is an adequate diagnostic tool to control the therapeutic effect of PPIs objectively and to identify non-responders at an early point.

Topics: Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Enzyme Inhibitors; Esomeprazole; Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Humans; Hypopharynx; Laryngeal Diseases; Male; Middle Aged; Pharyngeal Diseases; Prognosis; Treatment Outcome

The reflux disease questionnaire (RDQ) is a short, patient-completed instrument.. To investigate the psychometric characteristics of the RDQ in patients with heartburn-predominant (HB) and non-heartburn predominant (NHB) dyspepsia.. HB (n = 388) and NHB (n = 733) patients were randomized to esomeprazole 40 mg daily or twice daily for 1 week, followed by 3 weeks of esomeprazole 40 mg daily.. High factor loadings (0.78-0.86) supported the 'regurgitation' dimension of the RDQ. Overlapping factor loadings in the 'heartburn' and 'dyspepsia' dimensions suggested symptom overlap. All dimensions demonstrated high internal consistency (Cronbach's alpha: 0.79-0.90). Intra-class correlation coefficients over 4 weeks were good (0.66-0.85). The RDQ showed good responsiveness over 4 weeks of treatment, with high effect sizes (> or =0.80). Moderate or large symptom improvements were reported by 90% and 77% of HB and NHB patients, respectively, following treatment. Patients who responded to acid suppression also experienced symptom benefits in all RDQ dimensions.. The RDQ is reliable, valid and responsive to change in HB and NHB patients. The symptom overlap is important but need not play a major role in determining treatment strategy as both patient groups benefited from proton pump inhibitor treatment.

Topics: Adult; Anti-Ulcer Agents; Canada; Dyspepsia; Esomeprazole; Gastric Acid; Gastroesophageal Reflux; Heartburn; Humans; Male; Psychometrics; Surveys and Questionnaires

To observe the changes of dilated intercellular space (DIS) of esophageal epithelium in different subtypes of gastroesophageal reflux disease (GERD) before and after esomeprazole treatment.. Nineteen patients with GERD, 6 with erosive esophagitis (EE), 7 with NERD with abnormal acid exposure (NERD pH+), and 6 with NERD with normal acid exposure (NERD pH-), were treated with esomeprazole 40 mg daily for two months. During endoscopy before and after treatment, six biopsy specimens were taken from the apparently normal mucosa 3 - 5 cm above the dentate line in the esophagus to undergo HE staining and histological examination and transmission electron microscopy (TEM). Fifteen normal subjects were used as controls.. Two months after the treatment 5 cases (83.33%) in the EE group, 6 cases (85.57%) in the NERD pH+ group, and 5 cases (83.33%) in the NERD pH- group showed a complete recovery of DIS and complete disappearance of the symptom of heartburn. Two of the left three patients who showed incomplete recovery of DIS still had heartburn.. A complete recovery of DIS 2 months after treatment of esomeprazole is always accompanied by resolution of heartburn symptom. No significant difference in complete recovery of DIS can be found among different GERD subgroups.

Topics: Adult; Anti-Ulcer Agents; Epithelial Cells; Epithelium; Esomeprazole; Esophagus; Extracellular Space; Female; Gastroesophageal Reflux; Humans; Male; Matched-Pair Analysis; Microscopy, Electron, Transmission; Middle Aged; Prospective Studies

To evaluate the potential role of tegaserod in the management of functional dyspepsia (FD) and gastroesophageal reflux disease (GERD) in patients with chronic constipation and to determine the possible efficacy of tegaserod on solid-phase gastric emptying and gastric hypersensitivity.. This was an exploratory open-label trial of tegaserod therapy for dyspepsia and reflux symptoms in patients with chronic constipation. The study cohort consisted of 90 patients randomized to three treatment groups for a study period of 4 weeks (tegaserod 6 mg, twice daily; esomeprazole 40 mg, once daily; tegaserod 6 mg, twice daily plus esomeprazole 40 mg, once daily). Twenty healthy volunteers provided control values. Clinical symptoms were evaluated by one of the investigators using a Gastrointestinal Symptom Rating Scale (GSRS). Solid-phase gastric emptying and colonic transit were measured by the radiopaque barium marker method, and the water load test (WLT) was used to evaluate gastric sensation and the function of proximal stomach. The proportions of patients with complete relief of epigastric pain /discomfort, epigastric fullness, early satiety and heartburn in the tegaserod group and the tegaserod plus esomeprazole group were compared with the esomeprazole group, respectively.. The mean global gastrointestinal (GI) scores of all three treatment groups reported using the GSRS showed the same trend, with decreasing scores over the 4-week study period indicating a reported decreasing severity of symptoms that was significantly different from baseline values. Patients in the tegaserod plus esomeprazole group reported the lowest global GI scores after 4 weeks, as expected. Solid-phase gastric emptying (GER) and colonic transit (CTT) increased significantly in the tegaserod 6 mg twice daily group compared with baseline. These parameters did not change in the esomeprazole group at week 4 compared with baseline. In terms of gastric sensation, in the tegaserod group, the proportions of patients with hypersensitivity of the first perception threshold did not change at week 2 or week 4 compared with baseline; however, in this group and in the tegaserod plus esomeprazole group, the proportions of patients with hypersensitivity of discomfort threshold decreased significantly at week 4 compared with baseline. In the esomeprazole group, there were no changes in the proportions of patients with hypersensitivity of the first perception threshold and discomfort threshold at week 2 or 4 compared with baseline. No severe adverse events were recorded, and the medications were in general well-tolerated.. Tegaserod is effective and safe at improving dyspepsia and reflux symptoms in patients with chronic constipation, and tegaserod plus esomeprazole is superior to esomeprazole alone in the resolution of epigastric pain/discomfort and heartburn.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anti-Ulcer Agents; Chronic Disease; Cohort Studies; Constipation; Drug Therapy, Combination; Dyspepsia; Esomeprazole; Female; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Transit; Heartburn; Humans; Indoles; Male; Middle Aged; Serotonin 5-HT4 Receptor Agonists; Treatment Outcome

A prime concern for gastroesophageal reflux disease (GERD) patients is fast symptom control. Sparse valid information is available on the rapidity of the effect of proton pump inhibitors in providing symptom relief. The new reflux questionnaire ReQuest is validated for daily assessment of changes in GERD symptoms. Therefore, this study investigated the efficacy of 20 mg pantoprazole and 20 mg esomeprazole with regard to the time to symptom relief in patients with endoscopy-negative GERD (enGERD) using ReQuest.. 529 patients were treated with pantoprazole or esomeprazole over 4 weeks. ReQuest symptom scores were assessed daily. The mean and median times to first and sustained symptom relief were determined.. Median time to first symptom relief was 2 days for both drugs (intention-to-treat population). The median time to sustained symptom relief was 3 days shorter with pantoprazole (10.0 vs. 13.0 days). The Hodges-Lehmann estimator for the difference in time to reach first and sustained symptom relief between both groups was 0.00 days. For both variables the one-sided 95% CI (Moses) was [0.00; infinity[, documenting no significant differences between the treatment groups.. The rapidity of symptom control can be evaluated by clinically significant parameters using ReQuest. Pantoprazole and esomeprazole are equally effective in the time to first and sustained symptom relief.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Confidence Intervals; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Esomeprazole; Esophagoscopy; Female; Follow-Up Studies; Gastroesophageal Reflux; Gastroscopy; Humans; Male; Middle Aged; Pantoprazole; Probability; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Treatment Outcome

Little is known about the symptom course during and after treatment of gastroesophageal reflux disease (GERD). Here we address this question in patients with erosive GERD treated with pantoprazole or esomeprazole 40 mg once daily using the validated reflux questionnaire ReQuest.. Of 585 patients enrolled, 561 (intention-to-treat; ITT) patients with endoscopically confirmed GERD grades A-D (Los Angeles Classification) were randomized. To assess the GERD symptomatology, the patients completed the ReQuest daily, and analysis was done prior to (7 days), during (28 days), and after treatment (7 days). The mean scores (last 3 treatment days) of the subscale ReQuest(TM)-GI (gastrointestinal complaints) were compared between both groups. After the end of treatment, the number of symptom episodes and the rate of relapses were calculated.. Noninferiority of pantoprazole versus esomeprazole during treatment was shown (mean ReQuest-GI score). During the posttreatment period, the proportion of patients experiencing a symptomatic relapse (51 vs. 61%, p = 0.0216, ITT) and the number of symptom episodes (0.56 vs. 0.74, p = 0.0095, ITT) were significantly lower on pantoprazole than on esomeprazole.. Pantoprazole 40 mg was at least as effective as esomeprazole 40 mg for relieving GERD symptoms. During the posttreatment phase, patients on pantoprazole had a significantly lower risk to relapse and experienced significantly fewer symptom episodes.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Esomeprazole; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pantoprazole; Probability; Reference Values; Secondary Prevention; Sensitivity and Specificity; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

The outcome of gastro-oesophageal reflux disease treatment is traditionally assessed by measuring endoscopically confirmed healing and symptom relief separately. Both terms together, indicating complete remission, are intuitively a more realistic clinical endpoint but are assessed less often.. To explore this concept, we formally compared the efficacy of the proton pump inhibitors (PPIs) pantoprazole and esomeprazole using rates of complete remission judged against rates of healing and symptom relief separately.. Five hundred and eighty-two patients with erosive gastro-oesophageal reflux disease were randomized to treatment for 4, 8, or 12 weeks with either pantoprazole or esomeprazole 40 mg daily. Symptom relief was assessed with the validated ReQuesttrade mark-GI subscale.. Approximately 75% of patients were free of symptoms or had no oesophageal lesions after 4 weeks' treatment, rising to about 93% and 96%, respectively, at 12 weeks. Complete remission rates were, however, lower at these time points; approximately 60% and about 90%, respectively. Both PPIs had similar efficacy.. Endoscopically confirmed healing and symptom relief assessed separately over-estimated the benefits of both drugs. In contrast, complete remission indicates that patients may be treated inadequately when given the standard 4- to 8-week treatment. We suggest that complete remission is a more reliable and clinically relevant endpoint of treatment.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Anti-Ulcer Agents; Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pantoprazole; Remission Induction; Secondary Prevention; Treatment Outcome; Wound Healing

We studied spontaneous gastroesophageal reflux (GER)-induced esophageal distension using ultrasound imaging and its role in the genesis of esophageal symptoms before and during esomeprazole therapy. Ten controls and 10 GER disease (GERD) patients were studied by combined impedance, esophageal pH, manometry, and ultrasonography before and during esomeprazole therapy. Physiological data and symptoms were recorded for 2 h following a standardized meal. From ultrasound images, the esophageal cross-sectional area (CSA) at the peak of GER-induced distension was determined and compared between controls vs. patients, symptomatic vs. asymptomatic GER episodes, and before vs. during esomeprazole in GERD patients. The mean lumen CSA is greater in the patients than controls (271 +/- 71 mm(2) vs. 163 +/- 56 mm(2), P = 0.001) but not different among asymptomatic reflux episodes, and those associated with regurgitation (290 +/- 110 mm(2)) or heartburn (271 +/- 67 mm(2)). Eight chest pain episodes associated with reflux revealed a tendency toward larger mean esophageal distension (459 +/- 40 mm(2)) compared with asymptomatic reflux (268 +/- 70 mm(2), P = 0.058). Following esomeprazole treatment, most GER episodes were nonacidic and asymptomatic except in two patients in whom cyclical reflux was associated with large esophageal distensions. Esomeprazole did not alter the lumen CSA during GER. Esophageal distension is greater in the GERD subjects compared with controls; however, it is unlikely that the GER-induced distension of the esophagus plays a significant role in the genesis of heartburn sensation. Esomeprazole therapy does not alter the GER-induced distension of the esophagus.

Topics: Adult; Anti-Ulcer Agents; Case-Control Studies; Dilatation, Pathologic; Electric Impedance; Endosonography; Enzyme Inhibitors; Esomeprazole; Esophageal pH Monitoring; Esophagus; Female; Gastroesophageal Reflux; H(+)-K(+)-Exchanging ATPase; Heartburn; Humans; Hydrogen-Ion Concentration; Male; Manometry; Middle Aged; Pressure; Proton Pump Inhibitors; Treatment Outcome

Patient-reported outcome instruments are becoming increasingly important tools in clinical trials. We aimed to investigate the effect of baseline symptom severity on: (i) a global rating of change using the Overall Treatment Effect questionnaire; (ii) the change from baseline for some commonly used questionnaires, namely the Gastrointestinal Symptom Rating Scale and the Quality of Life in Reflux and Dyspepsia questionnaire; and (iii) treatment differences assessed by Gastrointestinal Symptom Rating Scale in patients with symptoms of gastroesophageal reflux disease.. We used pooled data from two 4-week studies of patients with gastroesophageal reflux disease (but without endoscopically verified esophagitis) randomized either to esomeprazole (20 or 40 mg) or to omeprazole 20 mg. We also used data from a study of omeprazole (10 or 20 mg) or ranitidine 300 mg in gastroesophageal reflux disease patients with or without esophagitis. The analysis is based on descriptive statistics.. Little impact of baseline symptoms/problems exists on the global rating of change (Overall Treatment Effect questionnaire). For example, the percentage of patients experiencing a large improvement with acid-suppressive therapy according to Overall Treatment Effect ranged from 63.2% for those with mild reflux at baseline to 70.3% for those with severe reflux. Change from baseline in the Gastrointestinal Symptom Rating Scale reflux dimension and quality of life in reflux and dyspepsia sleep disturbance and food/drink problems dimensions were associated with baseline symptoms/problems, with the largest change seen for patients with severe symptoms/problems at baseline. Baseline symptom severity was also associated with a clear effect on treatment differences, which tended to be larger for patients with severe symptoms than for patients with mild baseline symptoms.. In patients with gastroesophageal reflux disease, baseline symptom/problem severity had little association with the global rating of change, whereas a clear association with change in symptoms/problems and on treatment differences was apparent. The magnitude of change increased with increasing baseline severity of symptoms/problems.

Topics: Adult; Aged; Anti-Ulcer Agents; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Omeprazole; Prognosis; Quality of Life; Randomized Controlled Trials as Topic; Ranitidine; Severity of Illness Index; Treatment Outcome

Early identification of true responders to acid suppression in functional dyspepsia patients with symptoms of epigastric pain or burning may enable clinicians to optimally tailor treatment.. To evaluate whether a 1-w acid suppression trial is useful for identifying true responders in this population.. Patients (18-70 years) were randomized to either esomeprazole 40 mg q.d.s., b.d. or placebo for 1w, and then esomeprazole 40 mg q.d.s. or placebo for 7w. Epigastric pain and/or burning were recorded on a 4-point scale (0 = none, 3 = severe). Trial-week response was defined as symptom score sum < or = 1 on last 3d of therapy; response at 8w was symptom score sum < or = 1 over preceding 7d.. 1-w response rates were 33% (199 of 597), 29% (188 of 629) and 23% (71 of 315) with esomeprazole q.d.s., esomeprazole b.d. and placebo, respectively (P = 0.002 for esomeprazole groups vs. placebo). At 8w, trial week sensitivity and specificity were 46% and 80%, respectively, for esomeprazole (40 or 80 mg), and 33% and 87%, respectively, for placebo. The positive and negative predictive values for esomeprazole were 60% and 69%.. Response to a 1-w acid suppression trial is of limited use for predicting symptom response at 8w in patients with unexplained epigastric pain or burning.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Dyspepsia; Esomeprazole; Female; Follow-Up Studies; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Placebos; Quality of Life; Sensitivity and Specificity; Treatment Outcome

The primary objective was to assess the safety of esomeprazole 20 or 40 mg once daily in adolescents with clinically diagnosed gastroesophageal reflux disease (GERD). A secondary aim was to assess changes in GERD symptoms after esomeprazole therapy.. In this multicenter, randomized, double-blind study, adolescents ages 12 to 17 years inclusive received esomeprazole 20 or 40 mg once daily for 8 weeks. Adverse events and changes in clinical parameters (eg, physical examination, laboratory measurements) were evaluated to assess safety. Patients or their parents or guardians scored symptom severity daily, and investigators scored overall GERD symptom severity every 2 weeks using a 4-point scale.. In the 148 adolescents with safety data, treatment-related and non-treatment-related adverse events were reported by 75% and 78% of patients in the esomeprazole 20- and 40-mg groups, respectively. Twenty-two patients (14.9%) experienced adverse events that were considered related to treatment; the most common were headache (8%, 12/148), abdominal pain (3%, 4/148), nausea (2%, 3/148), and diarrhea (2%, 3/148). No serious adverse events or clinically important findings in other safety assessments were observed. At baseline, 68% (100/147) had heartburn, 63% (93/147) had epigastric pain, 57% (84/147) had acid regurgitation, and 15% (22/147) had vomiting symptoms. Symptom scores decreased significantly in both the esomeprazole 20-mg and 40-mg groups by the final study week (P < 0.0001). Investigators rated 63.1% (94/149) of the patients as having moderate or severe symptoms at baseline; at the final visit, this percentage decreased significantly to 9.3% (13/140; P < .0001).. In adolescent patients with GERD, esomeprazole 20 or 40 mg daily for 8 weeks was well tolerated, and GERD-related symptoms were significantly reduced from baseline values in both groups.

Topics: Abdominal Pain; Adolescent; Anti-Ulcer Agents; Child; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Headache; Heartburn; Humans; Male; Nausea; Severity of Illness Index; Treatment Outcome; Vomiting

To evaluate the pharmacokinetics and acid-suppressive effects of esomeprazole in infants with gastroesophageal reflux disease (GERD).. In this single-blind, randomized, parallel-group study, 50 infants 1 to 24 months old with symptoms of GERD, and >or=5% of time with intraesophageal pH <4 during 24-hour dual pH monitoring, received oral esomeprazole 0.25 mg/kg (n = 26) or 1 mg/kg (n = 24) once daily for 1 week. Intraesophageal and intragastric pH were recorded at 1 week, and blood samples were taken for pharmacokinetic analysis.. At baseline, mean percentages of time with intragastric pH >4 and intraesophageal pH <4 were 30.5% and 11.6%, respectively, in the esomeprazole 0.25 mg/kg group and 28.6% and 12.5% in the esomeprazole 1 mg/kg group. After 1 week of treatment, times with intragastric pH >4 were 47.9% and 69.3% in the esomeprazole 0.25 mg/kg and 1 mg/kg groups, respectively (P < 0.001 vs baseline), and times with intraesophageal pH <4 were 8.4% (P < 0.05 vs baseline) and 5.5% (P < 0.001 vs. baseline), respectively. The mean number of acid reflux episodes of >5 minutes duration decreased from 6 at baseline to 3 and 2 with esomeprazole 0.25 mg/kg and 1 mg/kg, respectively. The geometric mean AUC0-t of esomeprazole were 0.24 and 1.79 micromol x h/L for the 0.25 mg/kg and 1 mg/kg dosages of esomeprazole, respectively. Both esomeprazole dosages were well tolerated.. Oral treatment with esomeprazole 0.25 mg/kg and 1 mg/kg was well tolerated and provided dose-related acid suppression, dose-related exposure to esomeprazole, and decreased esophageal acid exposure in infants 1-24 months old with GERD.

Topics: Administration, Oral; Anti-Ulcer Agents; Area Under Curve; Australia; Child, Preschool; Dose-Response Relationship, Drug; Esomeprazole; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Infant, Newborn; Severity of Illness Index; Single-Blind Method; Time Factors; Treatment Outcome

We test the hypothesis that treatment of gastroesophageal reflux disease (GERD) can improve obstructive sleep apnea-hypopnea syndrome (OSAHS).. One hundred forty-six patients with OSAHS underwent a complete history-taking, physical examination, and laboratory testing, including questions related to GERD symptoms. Full-night attended polysomnography, 24-hour wireless pH study at the upper esophagus, snoring level evaluation, Epworth Sleepiness Scale, and quality-of-life surveys were completed for each patient. Patients who tested positive for GERD were treated with esomeprazole magnesium 40 mg once daily for 2 to 12 months. The 24-hour pH study was repeated, and those patients with elimination of GERD were reevaluated by polysomnography, snoring level evaluation, Epworth Sleepiness Scale, quality-of-life surveys, and subjective data collection.. Forty-one patients completed single-dose treatment with esomeprazole, but the repeat 24-hour pH study showed that 9 patients had persistent GERD. In the 29 patients who completed phase 2 with normal pH study findings, the snoring level decreased from 9.7 +/- 0.5 to 7.9 +/- 1.3 (p < .0001), the Epworth Sleepiness Scale score decreased from 14.2 +/- 2.5 to 11.1 +/- 2.4 (p < .0001), the apnea-hypopnea index decreased from 37.9 +/- 19.1 to 28.8 +/- 11.5 (p = .006), and the minimum saturation of oxygen increased from 84.1% +/- 7.8% to 86.9% +/- 5.0% (p = .055).. Treatment of GERD had a significant impact on the reduction of the apnea-hypopnea index, snoring, and daytime sleepiness. Elimination of GERD should be part of a comprehensive treatment plan for patients with OSAHS.

Topics: Administration, Oral; Adult; Disease Progression; Dose-Response Relationship, Drug; Enzyme Inhibitors; Esomeprazole; Esophagoscopy; Esophagus; Female; Gastric Acid; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Male; Polysomnography; Quality of Life; Sleep Apnea, Obstructive; Treatment Outcome

Acid suppression is the mainstay of therapy in gastro-oesophageal reflux disease. Esomeprazole 40 mg is more effective than lansoprazole 30 mg in healing mucosal lesions in severe erosive reflux oesophagitis. However, data comparing esomeprazole with lansoprazole in patients with complications of gastro-oesophageal reflux disease, such as ulcerative reflux oesophagitis and Barrett's oesophagus, are lacking.. To compare the efficacy of esomeprazole and lansoprazole at their standard dosages in suppressing oesophageal acid exposure in complicated gastro-oesophageal reflux disease.. Thirty patients with complicated gastro-oesophageal reflux disease (7 with ulcerative reflux oesophagitis and 23 with Barrett's oesophagus), randomly assigned to receive 40 mg esomeprazole (n=16) or 30 mg lansoprazole (n=14) once daily, underwent oesophageal 24-h pH monitoring while on therapy. Total, upright diurnal and supine nocturnal percentage acid reflux time were assessed.. Esomeprazole was significantly more effective than lansoprazole in decreasing oesophageal acid exposure. Normalisation of both total and supine nocturnal percentage acid reflux time was obtained in 12 of 16 (75%) patients treated with esomeprazole but only in 4 of 14 (28%) cases treated with lansoprazole (p=0.026).. Normalisation of oesophageal acid exposure can be achieved in the majority of complicated gastro-oesophageal reflux disease cases with esomeprazole 40 mg once daily.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Barrett Esophagus; Esomeprazole; Esophagitis, Peptic; Esophagus; Female; Gastric Acid; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Manometry; Middle Aged; Prospective Studies; Proton Pump Inhibitors

Gastroesophageal reflux disease (GERD) is common in patients with asthma, suggesting an interaction between the two conditions.. To assess the effect of gastric acid suppression with the proton pump inhibitor esomeprazole on asthma outcomes in subjects with persistent moderate to severe asthma treated with antiinflammatory asthma medication.. In this double-blind study, subjects were randomized to receive esomeprazole 40 mg or placebo twice daily for 16 wk. According to nocturnal respiratory symptoms (NOC) and GERD, subjects were divided into three strata: GERD-/NOC+, GERD+/NOC-, and GERD+/NOC+.. A total of 770 subjects were randomized. There was no statistically significant improvement in morning peak expiratory flow (PEF) over placebo in the overall study population: 6.3 L/min (p = 0.061). Over the whole treatment period, in GERD+/NOC+ subjects (n = 350), esomeprazole provided an 8.7-L/min improvement (p = 0.03) in morning PEF, and a 10.2-L/min improvement (p = 0.012) in evening PEF over placebo. Among 307 subjects taking long-acting beta2-agonists, improvements over placebo were observed in morning PEF (12.2 L/min, p = 0.017) and in evening PEF (11.1 L/min, p = 0.024); these improvements were more pronounced in GERD+/NOC+ subjects. Esomeprazole 40 mg twice daily was well tolerated and no safety concerns were noted.. Esomeprazole improved PEF in subjects with asthma who presented with both GERD and NOC. In subjects without both GERD and NOC, no improvement could be detected.

Topics: Administration, Oral; Adolescent; Adult; Aged; Asthma; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Probability; Prognosis; Reference Values; Respiratory Function Tests; Risk Assessment; Severity of Illness Index; Treatment Outcome

Proton pump inhibitor therapy has been reported to reduce proliferative changes of the oesophagus significantly in gastro-oesophageal reflux disease (GERD).. To assess the histological effects of esomeprazole treatment on the oesophagus.. Data were derived from a subgroup of patients participating in the proGERD study, who had either erosive reflux disease (n = 720) or non-erosive reflux disease (n = 35) and who had biopsy data from two sites [(i) 2 cm above the z-line and (ii) at the z-line], obtained at baseline and following treatment with esomeprazole. Proliferative changes of the squamous epithelium were assessed histologically by measuring thickness of the basal cell layer and elongation of the papillae as a percentage of the whole epithelial thickness.. In erosive reflux disease patients, the thickness of the basal cell layer and length of the papillae pretreatment were associated with the severity of oesophagitis (P < 0.05), at both biopsy sites. After esomeprazole treatment, baseline thickness and length of papillae were significantly reduced (P < 0.05) at both biopsy sites in non-erosive reflux disease and erosive reflux disease patients (particularly those with Los Angeles grades C and D).. This demonstrates a strong correlation between severity of GERD and histological parameters. Esomeprazole therapy resulted in clear reversal of proliferative changes observed prior to treatment in the squamous epithelium at both biopsy locations.

Topics: Adult; Biopsy; Cell Division; Enzyme Inhibitors; Epithelial Cells; Epithelium; Esomeprazole; Esophagitis, Peptic; Esophagoscopy; Esophagus; Female; Gastroesophageal Reflux; Humans; Male; Prospective Studies; Treatment Outcome

This article reports quality of life (QoL) aspects of a study that investigated the efficacy of three treatment regimens in gastro-oesophageal reflux disease patients. Following a 4-week symptom-control phase (esomeprazole 40 mg once daily), patients were randomised to 6 months' esomeprazole 20 mg once daily continuously (n = 658), on-demand (n = 634) or ranitidine 150 mg twice daily continuously (n = 610). Esomeprazole 40 mg once daily improved QoL during the symptom-control phase. At 6 months, both esomeprazole regimens were more effective than ranitidine in all dimensions of the Quality of Life in Reflux and Dyspepsia questionnaire (p < 0.0001). Esomeprazole continuous and on-demand led to a significant improvement in symptoms (Overall Treatment Evaluation questionnaire) compared with ranitidine (continuous: 80.2%, on-demand: 77.8%, vs. ranitidine 47.0%; p < 0.001). Esomeprazole once daily continuously maintained QoL better than esomeprazole on-demand and was associated with greater patient satisfaction. In conclusion, esomeprazole 20 mg once daily continuously and on-demand were more effective than ranitidine continuously for maintaining QoL.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Esomeprazole; Family Practice; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Proton Pump Inhibitors; Quality of Life; Ranitidine; Treatment Outcome

To evaluate the efficacy of acid-suppressive therapy with the proton pump inhibitor esomeprazole on the signs and symptoms of chronic posterior laryngitis (CPL) in patients with suspected reflux laryngitis.. Prospective, multicenter, randomized, parallel-group trial that compared twice-daily esomeprazole 40 mg with placebo for 16 weeks.. Eligible patients had a history of one or more CPL symptoms (throat clearing, cough, globus, sore throat, or hoarseness) and laryngoscopic signs indicating reflux laryngitis based on CPL index (CPLI) scores measured during a screening laryngoscopy. Patients were randomized to treatment if their 7-day screening diary-card recordings showed a cumulative primary symptom score of 9 or higher and they had 3 or more days with moderately severe symptoms based on a 7-point scale. Efficacy was assessed by changes in symptoms as recorded by patients and investigators and by changes in CPLI scores based on laryngoscopic examinations.. The patients' primary CPL symptom at final visit (primary efficacy end point) was resolved in 14.7% (14/95) and 16.0% (8/50) of patients in the esomeprazole and placebo groups, respectively (P=.799). Esomeprazole and placebo were not significantly different for change from baseline to the final visit in mean total CPLI (-1.66+/-2.13 vs. -2.0+/-2.55, respectively; P=.446) or any other secondary efficacy end points based on patient diary card or investigator assessments.. This study provides no evidence of a therapeutic benefit of treatment with esomeprazole 40 mg twice daily for 16 weeks compared with placebo for signs and symptoms associated with CPL.

Topics: Adult; Aged; Chronic Disease; Double-Blind Method; Enzyme Inhibitors; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Laryngitis; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Treatment Outcome

This open, randomized study (ONE: On-demand Nexium Evaluation) compared the two long-term management options with esomeprazole 20 mg--continuous daily or on-demand treatment--in endoscopically uninvestigated patients seeking primary care for symptoms suggestive of gastroesophageal reflux disease (GERD) who demonstrated complete relief of symptoms after four weeks of initial treatment with esomeprazole 40 mg. In total 1904 patients were randomized. During 26 weeks 913 patients received continuous daily therapy with esomeprazole 20 mg, once daily, while 991 patients were treated with esomeprazole 20 mg on-demand. The continuous therapy offered slightly better relief of the symptom heartburn, however esomeprazole 20 mg taken on-demand was associated with lower direct medical costs. Esomeprazole was generally well tolerated.

Topics: Adolescent; Adult; Anti-Ulcer Agents; Data Interpretation, Statistical; Endoscopy; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Patient Satisfaction; Patient Selection; Time Factors; Treatment Outcome

To compare esomeprazole with omeprazole for healing erosive esophagitis (EE), 1148 patients with endoscopically confirmed EE were randomized to once-daily esomeprazole, 40 mg, or omeprazole, 20 mg, for 8 weeks in this multicenter, double-blind, parallel-group trial. The primary outcome was the proportion of patients with healed EE at week 8. Secondary outcomes included diary and investigator assessments of heartburn symptoms. At week 8, estimated healing rates were 92.2% (95% CI, 89.9%-94.5%) with esomeprazole and 89.8% (95% CI, 87.2%-92.4%) with omeprazole. Healing rates with esomeprazole were significantly higher than those with omeprazole at weeks 8 (88.4% vs 77.5%; P = 0.007) and 4 (60.8% vs 47.9%; P = 0.02) in patients with moderate to severe (Los Angeles grade C or D) EE at baseline but were not significantly different for patients with mild (Los Angeles grade A or B) EE. Both treatments were comparable for other secondary measures and had similar tolerability profiles.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Double-Blind Method; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Omeprazole

The aim was to compare esomeprazole with lansoprazole for the maintenance of healed erosive esophagitis and resolution of gastroesophageal reflux disease-related symptoms in a United States population.. Patients who entered this double-blind, randomized, parallel-group, multicenter, maintenance trial had been treated and healed (no endoscopic evidence of erosive esophagitis) with esomeprazole 40 mg or lansoprazole 30 mg once daily (patients with Los Angeles grades C and D erosive esophagitis at baseline) or esomeprazole 40 mg (patients with Los Angeles grades A and B erosive esophagitis at baseline) and had no heartburn or acid regurgitation symptoms during the previous week. Patients were randomized to maintenance once-daily therapy with esomeprazole 20 mg (n = 512) or lansoprazole 15 mg (n = 514) for up to 6 months. Esophago-gastroduodenoscopies were done at months 3 and 6, and investigators assessed symptom severity at months 1, 3, and 6. Endoscopic/symptomatic remission was defined as no erosive esophagitis and no study withdrawal as a result of reflux symptoms.. The estimated endoscopic/symptomatic remission rate during a period of 6 months was significantly higher (P = .0007) for patients who received esomeprazole 20 mg once daily (84.8%) compared with those who received lansoprazole 15 mg (75.9%). Most patients had no heartburn (383/462 and 369/466) or acid regurgitation (401/462 and 400/466) symptoms at 6 months, and there were no significant differences between treatments. Both treatments were well-tolerated.. Esomeprazole 20 mg is more effective than lansoprazole 15 mg in maintaining endoscopic/symptomatic remission in patients with healed erosive esophagitis.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Endoscopy, Digestive System; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Middle Aged; Treatment Outcome

The aim of this study was to assess the pharmacokinetic (PK) properties and tolerability of esomeprazole 20 and 40 mg after single and repeated oral doses in adolescents with symptoms of gastroesophageal reflux disease (GERD).. The study included 15 boys and 13 girls (mean age, 14.3 years). Geometric mean AUC(0-infinity) values (overall drug exposure) were 1.58 and 5.57 micromol . h/L (0.027 and 0.083 pmol x h x L(-1)/kg) after single-dose administration of esomeprazole 20 and 40 mg, respectively, on day 1. Corresponding values with repeated doses (day 8) were 3.65 and 13.86 micromol x h/L (0.064 and 0.207 micromol x h x L(-1)/kg). Geometric mean Cmax values were 0.67 and 2.78 micromol/L (0.012 and 0.041 micromol/L x kg(-1)) with single-dose administration of esomeprazole 20 and 40 mg, respectively, and 1.45 and 5.13 micromol/L (0.026 and 0.075 micromol/L x kg(-1)), respectively, with repeated doses (day 8). These mean AUC(0-infinity) and CmaX values were >2-fold with the 40 mg dose compared with the 20-mg dose with single- and repeated-dose administration. The most common adverse event was headache (2 [7.1%] patients).. The results of this study suggest that the PK parameters of esomeprazole were both dose- and time-dependent in these adolescents with GERD. Both doses of esomeprazole were well tolerated in this study population.

Topics: Adolescent; Anti-Ulcer Agents; Child; Dose-Response Relationship, Drug; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Time Factors; Treatment Outcome

The objective of this trial was to compare the efficacy of esomeprazole, 20 mg, with that of omeprazole, 20 mg, in patients with erosive esophagitis (EE). In this multicenter, double-blind, parallel-group trial, 1176 patients with EE confirmed by endoscopy (Helicobacter pylori-negative by serology) were randomized to once-daily treatment with 20 mg esomeprazole or 20 mg omeprazole for 8 weeks. The primary outcome was the proportion of patients with healed EE through week 8. Secondary outcomes included diary and investigator assessments of heartburn symptoms. Cumulative life-table healing rates at week 8 were similarly high for 20 mg esomeprazole (90.6%; 95% confidence interval, 88.1%-93%) and 20 mg omeprazole (88.3%; 95% confidence interval, 85.5%-91.0%). The two treatments were comparable for other secondary measures and had similar tolerability profiles.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Double-Blind Method; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Omeprazole

The aim of this study was to compare the efficacy of esomeprazole and pantoprazole with regard to healing and relief from gastroesophageal reflux disease-related symptoms. I this multicentre, randomized, single-blind study 180 patients (ITT population) diagnosed with endoscopically proven GERD grade A,B,C received esomeprazole (40 mg once daily (o.d.), n = 90) orpantoprazole (40 mg o.d., n = 90). Healing and relief from GERD-related symptoms were assessed at first and final visit (after 4 or 8 weeks of treatment). Esomeprazole 40 mg provided significantly greater healing than pantoprazole 40 mg after 4 weeks of treatment in patients with EE (77.8% vs. 72.2%). Esomeprazole-treated patients were healed after up to 8 weeks of treatment similar those treated with pantoprazole (92.2% vs. 91.1%). The proportion of heartburn-free days was similar in patients treated with esomeprazole and to those treated with pantoprazole.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Aged; Anti-Ulcer Agents; Benzimidazoles; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pantoprazole; Severity of Illness Index; Sulfoxides; Treatment Outcome

The aim of this study was to assess the overall exposure, other pharmacokinetic (PK) properties, and tolerability of esomeprazole magnesium after repeated oral doses of 5, 10, and 20 mg in pediatric patients who had symptoms of gastroesophageal reflux disease (GERD).. This randomized, open-label study was conducted at West Coast Clinical Trials, Long Beach, California. Boys and girls aged 1 to 11 years who had a clinical diagnosis of GERD were included and stratified by age (1-5 years [younger group] and 6-11 years [older group]). For this 5-day study, children in the younger group were randomly assigned to receive 1 esomeprazole 5- or 10-mg capsule p.o. QD, and those in the older group were randomly assigned to receive 1 esomeprazole 10- or 20-mg capsule p.o. QD. On days 1 to 4, study medications were administered with the supervision of the study personnel 1 hour before breakfast. Blood samples were collected within 0.5 hour before and 0.5, 1, 1.5, 2, 3, 4, 5, and 6 hours after study drug administration on day 5. Plasma concentrations of esomeprazole were measured using reverse-phase liquid chromatography and mass-spectrometric detection. Tolerability assessments were performed by reviewing the number and severity of adverse events (collected via spontaneous reporting and direct questioning) and findings from the physical examination, which included vital-sign measurements and laboratory analysis (hematology, biochemistry, and urinalysis). Site personnel supervised the administration of the study drug to ensure compliance with treatment.. The study included 31 children (17 boys, 14 girls; mean age, 5 years; 18 children in the younger group, 13 in the older group). A total of 27 children were included in the PK analysis. In the younger group, the geometric mean AUC(0-infinity) and Cmax values in the esomeprazole 10-mg group were >2-fold that in the 5-mg group (AUC(0-infinity), 4.83 and 0.74 pmol x h/L [0.32 and 0.04 micromol x h x L(-1)/kg], respectively; Cmax, 2.98 and 0.62 micromol/L [0.19 and 0.03 micromol/L x kg(-1)], respectively). In the older group, the geometric mean AUC(0-infinity) and Cmax values for the 20-mg dose group were approximately 2-fold those for the 10-mg dose group (AUC(0-infinity), 6.28 and 3.70 micromol x h/L [0.21 and 0.12 pmol x h x L(-1)/kg], respectively; Cmax, 3.73 and 1.77 micromol/L [0.13 and 0.06 micromol/L x kg 1], respectively). For the 10-mg esomeprazole dose, the geometric mean body-weight-normalized apparent oral clearance was approximately 50% higher in the younger group compared with the older group (0.40 and 0.25 L/h x kg(-1), respectively). Thirty patients were included in the tolerability analysis. The adverse events that occurred were skin excoriation, discolored feces, and skin laceration (1 [3.3%] patient each); none were considered related to treatment.. The results of this small study suggest that, in children aged 1 to 11 years who had GERD, the PK properties of esomeprazole may be both dose and age dependent and that younger children might have a more rapid metabolism of esomeprazole per kilogram of body weight compared with older children. Esomeprazole was well tolerated at doses of 5, 10, and 20 mg in the pediatric patients studied.

Topics: Administration, Oral; Age Factors; Child; Child, Preschool; Enzyme Inhibitors; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Infant; Male

Little is known about the symptom course during and after treatment of gastroesophageal reflux disease (GERD). Here we address this question in patients with erosive GERD treated with pantoprazole or esomeprazole 40 mg once daily using the validated reflux questionnaire ReQuest.. Of 585 patients enrolled, 561 (intention-to-treat; ITT) patients with endoscopically confirmed GERD grades A-D (Los Angeles Classification) were randomized. To assess the GERD symptomatology, the patients completed the ReQuest daily, and analysis was done prior to (7 days), during (28 days), and after treatment (7 days). The mean scores (last 3 treatment days) of the subscale ReQuest-GI (gastrointestinal complaints) were compared between both groups. After the end of treatment, the number of symptom episodes and the rate of relapses were calculated.. Noninferiority of pantoprazole versus esomeprazole during treatment was shown (mean ReQuest-GI score). During the posttreatment period, the proportion of patients experiencing a symptomatic relapse (51 vs. 61%, p = 0.0216, ITT) and the number of symptom episodes (0.56 vs. 0.74, p = 0.0095, ITT) were significantly lower on pantoprazole than on esomeprazole.. Pantoprazole 40 mg was at least as effective as esomeprazole 40 mg for relieving GERD symptoms. During the posttreatment phase, patients on pantoprazole had a significantly lower risk to relapse and experienced significantly fewer symptom episodes.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adult; Aged; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Esomeprazole; Esophagoscopy; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pain Measurement; Pantoprazole; Patient Satisfaction; Probability; Reference Values; Risk Assessment; Secondary Prevention; Severity of Illness Index; Treatment Outcome

To assess the efficacy of the 8-week therapy with esomeprazole 40 mg vs. pantoprazole 40 mg for healing erosive oesophagitis (EE) as part of a management study.. Patients had a history of gastro-oesophageal reflux disease symptoms (> or =6 months) and had suffered heartburn on at least 4 of the 7 days preceding enrollment. Endoscopies were performed to grade EE severity using the Los Angeles (LA) classification system at baseline, 4 and 8 weeks (if unhealed at 4 weeks). Heartburn severity was recorded by patients on diary cards. The primary end point was healing of EE by week 8 of treatment.. Of 3170 patients randomized, the intent-to-treat population consisted of 3151 patients (63% male, mean age: 50.6 years, 27% Helicobacter pylori-positive). Esomeprazole 40 mg healed a significantly greater proportion of EE patients than pantoprazole 40 mg at both 4 weeks (life table estimates: esomeprazole 81%, pantoprazole 75%, P < 0.001) and 8 weeks (life table estimates: esomeprazole 96%, pantoprazole 92%, P < 0.001). The median time to reach sustained heartburn resolution was 6 days in patients receiving esomeprazole and 8 days with pantoprazole (P < 0.001).. Esomeprazole 40 mg is more effective than pantoprazole 40 mg for healing EE and providing resolution of associated heartburn.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Benzimidazoles; Double-Blind Method; Esomeprazole; Esophagitis; Female; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Pantoprazole; Sulfoxides; Treatment Outcome

The real-life clinical setting has been known to provide, sometimes, results different from controlled study outcomes. IPEP (InPractice Evaluation Program) was designed to evaluate the efficacy of esomeprazole in providing symptom relief in patients with reflux disease who present to primary care physicians for heartburn and symptoms that are poorly controlled by other drugs, thus testing the efficacy of the drug in day-to-day practice.. 119 primary care physicians and 22 internal medicine specialists, widely distributed geographically, participated in the program. The frequency and severity of three symptoms (heartburn, acid regurgitation and upper abdominal pain) were assessed before and at the end of one month treatment with esomeprazole 40 mg once daily.. Follow-up data from 747 patients enrolled in IPEP was available to evaluate the efficacy of the intervention. Over 80% of the enrolled patients reported a decrease in the frequency of symptoms to less than one episode per week for all the three major symptoms (heartburn, acid regurgitation and upper abdominal pain). Regarding the severity of symptoms, 50-60% of the patients reported total relief, while 30-40% reported persistence of symptoms, but admitted them to be milder and with lower frequency. At the end of treatment, no patient reported severe or extremely severe symptoms.. The results of this routine clinical practice program are consistent with data reported in controlled trials indicating the efficacy of esomeprazole even in patients with upper gastrointestinal symptoms "refractory" to treatments prescribed by primary care practitioners.

Topics: Administration, Oral; Adult; Enzyme Inhibitors; Esomeprazole; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Primary Health Care; Severity of Illness Index; Treatment Outcome

Upper gastrointestinal (GI) symptoms are common in patients using non-steroidal antiinflammatory drugs (NSAIDs) including selective cyclooxygenase (COX)-2 inhibitors and may be acid related. We therefore assessed esomeprazole treatment for upper GI symptoms in these patients.. A total of 794 and 848 continuous NSAID users, free of gastroduodenal ulcers, erosive esophagitis, and Helicobacter pylori, were enrolled into two identical, multinational, multicenter double-blind studies (NASA1, SPACE1). Moreover, 608 and 556 patients were randomized to receive 4 wk esomeprazole 20 mg, or 40 mg, or placebo once daily. The primary variable was the patient-reported change in the upper GI symptom (pain, discomfort, or burning in the upper abdomen) score on a 7-graded severity scale (0-6) from the 7 days prior to treatment to the last 7 days in the study.. Esomeprazole was associated with highly significant symptom improvement compared to placebo. Symptom improvements were 2.30 mean [SD 1.63] on esomeprazole 20 mg and 2.03 [1.56] on esomeprazole 40 mg versus 1.64 [1.57] on placebo in NASA1 and 2.17 [1.34] and 2.12 [1.48]versus 1.56 [1.26], respectively, in SPACE1 (all placebo comparisons at least p < 0.001). Esomeprazole-improved symptoms in patients taking selective COX-2 inhibitors, with changes of 2.21 [1.46] and 1.92 [1.38]versus 1.64 [1.46] in NASA1 and 2.20 [1.26] and 2.24 [1.62]versus 1.58 [1.37] in SPACE1 (all placebo comparisons at least p < 0.05), as well as those on non-selective NSAIDs. Esomeprazole was well tolerated and associated with significant improvements in HRQL.. Esomeprazole 20 mg and 40 mg improve upper GI symptoms associated with continuous, daily NSAID therapy, including selective COX-2 inhibitors.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Double-Blind Method; Esomeprazole; Female; Follow-Up Studies; Gastroesophageal Reflux; Heartburn; Humans; Isoenzymes; Male; Membrane Proteins; Middle Aged; Nausea; Pain; Peroxidases; Placebos; Prostaglandin-Endoperoxide Synthases; Quality of Life; Treatment Outcome; Upper Gastrointestinal Tract

A prime concern for gastroesophageal reflux disease (GERD) patients is fast symptom control. Sparse valid information is available on the rapidity of the effect of proton pump inhibitors in provid ing symptom relief. The new reflux questionnaire ReQuest is validated for daily assessment of changes in GERD symptoms. Therefore, this study investigated the efficacy of 20 mg pantoprazole and 20 mg esomeprazole with regard to the time to symptom relief in patients with endoscopy-negative GERD (enGERD) using ReQuest.. 529 patients were treated with pantoprazole or esomeprazole over 4 weeks. ReQuest symptom scores were assessed daily. The mean and median times to first and sustained symptom relief were determined.. Median time to first symptom relief was 2 days for both drugs (intention-to-treat population). The median time to sustained symptom relief was 3 days shorter with pantoprazole (10.0 vs. 13.0 days). The Hodges-Lehmann estimator for the difference in time to reach first and sustained symptom relief between both groups was 0.00 days. For both variables the one-sided 95% CI (Moses) was [0.00; infinity] documenting no significant differences between the treatment groups.. The rapidity of symptom control can be evaluated by clinically significant parameters using ReQuest. Pantoprazole and esomeprazole are equally effective in the time to first and sustained symptom relief.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Double-Blind Method; Endoscopy, Gastrointestinal; Esomeprazole; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pantoprazole; Quality of Life; Safety; Severity of Illness Index; Sulfoxides; Surveys and Questionnaires; Treatment Outcome

Gastro-esophageal reflux disease (GERD) is becoming increasingly common in Asia. Data on the efficacy of proton pump inhibitors in patients with non-erosive GERD (NERD) in Asia is lacking. This double-blind study compared the efficacy and safety of rabeprazole with esomeprazole in relief of symptoms in patients with NERD.. One hundred and thirty-four patients with reflux symptoms of NERD and normal endoscopy were randomized to receive rabeprazole 10 mg or esomeprazole 20 mg once daily for 4 wk. Symptoms were recorded in a diary and changes in severity of symptoms noted.. At 4 wk of treatment, rabeprazole 10 mg and esomeprazole 20 mg were comparable with regards to the primary endpoint of time to achieve 24-h symptom-free interval for heartburn 8.5 d vs 9 d and regurgitation 6 d vs 7.5 d. Rabeprazole and esomeprazole were also similarly efficacious in term of patient's global evaluation with 96% of patients on rabeprazole and 87.9% of patients on esomeprazole, reporting that symptoms improved (P = NS). Satisfactory relief of day- and night-time symptoms was achieved in 98% of patients receiving rabeprazole and 81.4% of patients receiving esomeprazole. Adverse events were comparable in both groups (P = NS).. Rabeprazole 10 mg has a similar efficacy and safety profile in Asians with NERD as esomeprazole 20 mg. Further study is necessary to investigate whether the small differences between the two drugs seen in this study are related to the improved pharmacodynamic properties of rabeprazole. Both drugs were well tolerated.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Benzimidazoles; Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Rabeprazole

This study assesses the difference in direct medical costs between on-demand treatment with esomeprazole 20 mg, continuous treatment with esomeprazole 20 mg once-daily and continuous treatment with ranitidine 150 mg twice-daily to prevent symptomatic relapse in patients with gastroesophageal reflux disease over 26 weeks. Two hundred eighty-one GP clinics in Norway enrolled 2156 patients to an open, randomized, parallel group, Norwegian society perspective study during 2000-2001. The total direct medical costs of each strategy were 171.9 Euros for on-demand esomeprazole (n = 634), 221.6 Euros for ranitidine (n = 610) and 248.8 Euros for continuous esomeprazole (n = 658). The total costs for on-demand and continuous esomeprazole treatment and ranitidine treatment were 221.5, 286.5 and 295.8 Euros, respectively. The highest proportion of costs was because of the study medication cost in each strategy. The on-demand and continuous treatment strategies with esomeprazole were found to be cost-effective, compared with ranitidine.

Topics: Adult; Anti-Ulcer Agents; Cost-Benefit Analysis; Drug Costs; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Long-Term Care; Male; Middle Aged; Norway; Patient Satisfaction; Prospective Studies; Proton Pump Inhibitors; Ranitidine

One option for patients with symptoms of gastroesophageal reflux disease (GERD) is treatment with proton pump inhibitors without prior endoscopy. Continuous or on-demand maintenance therapy are options for symptom-free patients. This study assessed the efficacy of three different treatment options in GERD patients in Norway. About 395 General Practitioners enrolled 2156 patients with symptoms of GERD in an open, randomised, parallel group trial. Following a 4-week symptom control phase [esomeprazole 40 mg once daily (od)], patients received either esomeprazole 20 mg od continuously or on-demand or ranitidine 150 mg twice-daily continuously for 6 months. The percentage of patients with no heartburn at the end of the study was maintained most effectively in the esomeprazole 20 mg continuous group (72.2%) and least effectively in the ranitidine group (32.5%). Significantly, more patients were completely/very satisfied with esomeprazole continuous (82.2%) and esomeprazole on-demand (75.4%) than with ranitidine continuous (33.5%) treatment (p < 0.0001). More patients were kept in remission, symptom free and were overall more satisfied with esomeprazole treatment than ranitidine.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Drug Administration Schedule; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Long-Term Care; Male; Middle Aged; Norway; Patient Satisfaction; Prospective Studies; Proton Pump Inhibitors

Intragastric acid suppression is the most direct measure of the pharmacodynamic efficacy of proton pump inhibitors, which are the most effective drugs for acid-related diseases.. To compare the effectiveness of once and twice daily dosing of lansoprazole and esomeprazole in controlling intragastric acidity (target gastric pH > 4.0) over a 24-hour period.. In an open-label, two-way crossover study, 45 Helicobacter pylori-negative patients with gastro-oesophageal reflux disease were randomized to receive one of two regimens: 30 mg lansoprazole or esomeprazole 40 mg once daily. Intragastric pH was assessed by 24-hour pH monitoring on day 5 of each regimen. Dosing was increased to twice daily and pH was reassessed on day 10. Following a 14-day washout, patients were crossed over to the other medication and the dosage regimens and pH assessments were repeated.. Data were analysed from 35 patients who completed all scheduled assessments and had 24-hour monitoring for each end-point. Mean time pH > 4.0 and mean 24-hour pH were highest for esomeprazole 40 mg twice daily, followed by lansoprazole 30 mg twice daily, esomeprazole 40 mg once daily and lansoprazole 30 mg once daily. Esomeprazole 40 mg twice daily provided superior control of intragastric pH compared with either once or twice daily dosing of lansoprazole and once daily dosing of esomeprazole (P < 0.01). Esomeprazole 40 mg once daily was comparable with lansoprazole 30 mg twice daily and both were superior to lansoprazole 30 mg once daily (P < 0.01).. Response to acid suppression treatment depends on the treatment selected. Esomeprazole 40 mg twice daily provided better control of intragastric pH than all other regimens evaluated. Esomeprazole 40 mg daily, however, was comparable with lansoprazole 30 mg twice daily and superior to lansoprazole 30 mg once daily.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Anti-Ulcer Agents; Circadian Rhythm; Cross-Over Studies; Esomeprazole; Female; Gastric Acid; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Middle Aged; Treatment Outcome

Quality of life has been assessed in a large, multicentre randomized, open label study.. To evaluate the economic and clinical consequences of two different maintenance treatment modalities, administered to 6017 gastro-oesophageal reflux disease patients at 451 gastroenterological centres in Italy.. Adult gastro-oesophageal reflux disease patients received, at enrolment, an acute treatment of esomeprazole 40 mg/day for 4 weeks and, if successfully treated, were randomized into two maintenance treatment strategies: esomeprazole 20 mg/day or esomeprazole on demand for 6 months. A baseline endoscopy allowed the exclusion of grade II-IV oesophagitis according to Savary-Miller's classification. Burden of gastro-oesophageal reflux disease was measured at baseline by the generic questionnaire Short-Form 36 and by a disease specific instrument, quality of life in reflux and dyspepsia (QOLRAD), also administered at start and conclusion of maintenance period. Investigators were required to collect patient judgement about the degree of satisfaction with treatment effect on heartburn, with a 7-point scale.. A comparison between Short-Form 36 scores and the normative source of the Italian general population suggested that symptomatic gastro-oesophageal reflux disease patients experience a worse quality of life than the general population. At the end of the 4-week treatment with esomeprazole 40 mg all (QOLRAD) dimensions showed a statistically significant (P < 0.0001) and clinically meaningful improvement. Satisfaction level towards treatment was reported high in the total enrolled population after acute treatment with esomeprazole 40 mg/day (96.2% satisfied and 64.4% very satisfied). A statistically significant difference in (QOLRAD) scores was registered at the end of maintenance phase in favour of the continuous regimen, nevertheless the size of this difference was very small in all dimensions; similarly, the proportion of patients very satisfied was slightly higher in the continuous treatment arm (64.5%) than in the on-demand arm (59.7%).. Gastro-oesophageal reflux disease can significantly impair health-related quality of life and esomeprazole therapy allows immediate relief in the acute phase of the disease. Quality of life improvement was maintained during the 6-month follow-up with a slight difference in term of quality of life in reflux and dyspepsia scores and patients' satisfaction in favour of the continuous treatment strategy.

Topics: Acute Disease; Anti-Ulcer Agents; Cost of Illness; Dose-Response Relationship, Drug; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Patient Satisfaction; Quality of Life; Treatment Outcome

Sleep disturbances are common in patients with gastroesophageal reflux disease (GERD). This study examined the effects of esomeprazole on nighttime heartburn, GERD-related sleep disturbances, sleep quality, work productivity, and regular activities.. This multicenter, randomized, double-blind, placebo-controlled trial included adults with GERD-associated sleep disturbances and moderate-to-severe nighttime heartburn (recorded by patient diary during screening). Patients received oral esomeprazole 40 mg (n = 220) or 20 mg (n = 226) or placebo (n = 229) once daily for 4 wk. The primary outcome was relief of nighttime heartburn. Secondary outcomes included resolution of sleep disturbances, sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and work productivity measured by the Work Productivity and Activity Impairment Questionnaire.. Nighttime heartburn was relieved in 53.1% (111/209), 50.5% (111/220), and 12.7% (28/221) of patients who received esomeprazole 40 mg, esomeprazole 20 mg, and placebo, respectively. Differences (95% CI) versus placebo were 40.5% (32.4%, 48.5%) and 37.8% (29.9%, 45.7%) and were highly significant (p < 0.0001). GERD-related sleep disturbances resolved in significantly more (p < 0.0001) patients who received esomeprazole 40 (73.7%) or 20 mg (73.2%) than in those who received placebo (41.2%). Both esomeprazole groups had greater PSQI global score changes from baseline (p < 0.0001 vs placebo) and more (p < 0.0001 vs placebo) work hours saved per week per patient compared with baseline (esomeprazole 40 mg, 11.6 h; esomeprazole 20 mg, 12.3 h; placebo, 6.2 h).. Esomeprazole reduced nighttime heartburn and GERD-related sleep disturbances and improved sleep quality and work productivity.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Double-Blind Method; Efficiency; Esomeprazole; Female; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Sleep; Surveys and Questionnaires; Treatment Outcome

Following initial healing of erosive oesophagitis, most patients require maintenance therapy to prevent relapse.. To compare endoscopic and symptomatic remission rates over 6 months' maintenance therapy with esomeprazole or pantoprazole (both 20 mg once daily) in patients with healed erosive oesophagitis.. Patients with symptoms of gastro-oesophageal reflux disease and endoscopically confirmed erosive oesophagitis at baseline were randomized to receive esomeprazole 40 mg or pantoprazole 40 mg for up to 8 weeks. Patients with healed erosive oesophagitis and free of moderate/severe heartburn and acid regurgitation at 4 weeks or, if necessary, 8 weeks entered the 6-month maintenance therapy phase of the study.. A total of 2766 patients (63% men; mean age 50 years) received esomeprazole 20 mg (n = 1377) or pantoprazole 20 mg (n = 1389) and comprised the intention-to-treat population. Following 6 months of treatment, the proportion of patients in endoscopic and symptomatic remission was significantly greater for those receiving esomeprazole 20 mg (87.0%) than pantoprazole 20 mg (74.9%, log-rank test P < 0.0001). Esomeprazole 20 mg produced a higher proportion of patients free of moderate to severe gastro-oesophageal reflux disease symptoms and fewer discontinuations because of symptoms than pantoprazole 20 mg (92.2% vs. 88.5%, P < 0.001).. Esomeprazole 20 mg is more effective than pantoprazole 20 mg for maintenance therapy following initial healing of erosive oesophagitis and relief of gastro-oesophageal reflux disease symptoms.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Double-Blind Method; Drug Tolerance; Enzyme Inhibitors; Esomeprazole; Esophagitis, Peptic; Esophagoscopy; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pantoprazole; Proton Pump Inhibitors; Secondary Prevention; Sulfoxides; Treatment Outcome

Intravenous esomeprazole may be beneficial for patients who cannot take oral medications.. To compare intravenous esomeprazole with oral esomeprazole for effects on maximal acid output during pentagastrin stimulation in patients with gastro-oesophageal reflux disease symptoms.. In four separate open-label, randomized, two-way crossover studies, adult patients were administered esomeprazole 20 or 40 mg once daily either orally or intravenously (by 15-min infusion or 3-min injection) for 10 days and switched to the other formulation with no washout period. Basal acid output and maximal acid output were measured on days 11, 13 and 21.. In the four studies (total of 183 patients), least-squares mean maximal acid output ranged from 3.0 to 4.1 mmol/h after intravenous esomeprazole 40 or 20 mg and from 2.2 to 3.3 mmol/h after oral esomeprazole 20 or 40 mg. Differences between formulations were small and not statistically significant but did not meet the prospectively defined criterion for non-inferiority of the intravenous formulation. Median basal acid output values ranged from 0.04 to 0.27 mmol/h after intravenous administration and from 0.05 to 0.25 mmol/h after oral esomeprazole.. Intravenous esomeprazole is an acceptable alternative to the oral formulation for treatment of up to 10 days of duration.

Topics: Administration, Oral; Adolescent; Adult; Aged; Cross-Over Studies; Enzyme Inhibitors; Esomeprazole; Esophagitis, Peptic; Female; Gastric Acid; Gastroesophageal Reflux; Humans; Infusions, Intravenous; Male; Middle Aged; Proton Pump Inhibitors; Sex Factors; Treatment Outcome

The clinical outcome of acid-related disorders treated by proton pump inhibitors (PPIs) might be dependent on the polymorphically expressed cytochrome P450 (CYP) 2C19, which is involved in PPI metabolism. We tested whether esomeprazole-induced healing of gastroesophageal reflux disease (GERD) is related to CYP2C19 genotype.. Two hundred five patients with GERD (Los Angeles classification grade A or B) were included in a case-control study according to endoscopic outcome (healed versus unhealed group, matched for confounders) after treatment with 40 mg esomeprazole daily for 4 weeks. The frequency of CYP2C19 genotypes was determined as the primary outcome measure for both groups. In a second trial plasma levels of esomeprazole and corresponding CYP2C19 and CYP3A4 metabolites (5-hydroxyomeprazole and omeprazole sulfone) were monitored in 10 CYP2C19 wild-type patients with GERD after the first and last doses (day 7) of 40 mg esomeprazole daily to calculate metabolic ratios.. CYP2C19 wild-type (n = 148) and heterozygous (n = 51) or homozygous variant (n = 6) patients did not differ with respect to baseline characteristics. The frequency distribution of CYP2C19 genotypes was not different between patients with complete (75/100) and incomplete (73/105) healing (P = .65). When a single esomeprazole dose and multiple dosing were compared, the low contribution of CYP2C19 to the elimination of esomeprazole decreased further by 50%. In contrast, the CYP3A4-dependent formation of omeprazole sulfone increased by 40%, and consequently, the metabolic ratio of omeprazole sulfone to 5-hydroxyomeprazole was elevated from 7.9 to 19.3 (P = .0004).. In contrast to other PPIs, esomeprazole-induced healing of GERD is unrelated to the CYP2C19 genotype, which can be explained by the metabolic shift toward the CYP3A4-mediated pathway.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adult; Aged; Area Under Curve; Aryl Hydrocarbon Hydroxylases; Case-Control Studies; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Enzyme Inhibitors; Esomeprazole; Female; Gastroesophageal Reflux; Genotype; H(+)-K(+)-Exchanging ATPase; Half-Life; Humans; Male; Middle Aged; Mixed Function Oxygenases; Omeprazole; Prospective Studies; Proton Pump Inhibitors; Time Factors

A prospective, open, randomized multi-centre study with parallel group design was conducted in 155 general practice clinics, and included 1357 endoscopically uninvestigated patients with symptoms suggestive of gastro-oesophageal reflux disease.. To assess the differences in direct medical costs between a patient-controlled on-demand treatment strategy with esomeprazole, 20 mg daily, and general practitioner-controlled intermittent treatment strategies with esomeprazole, 40 mg daily, for either 2 or 4 weeks. Secondary objectives were to measure other costs, total costs, patient satisfaction and time to first relapse.. The primary cost analysis was carried out as a cost minimization analysis, comparing the direct medical costs in patients allocated to on-demand treatment vs. those in patients allocated to either of the intermittent treatment strategies.. The mean direct medical costs were 182, 221 and 195 euros for patient-controlled on-demand treatment and 2 weeks and 4 weeks of general practitioner-controlled intermittent treatment, respectively, showing no statistically significant difference. The comparable mean total costs were 211, 344 and 300 euros, i.e. significantly lower for patients treated on-demand compared with either of the general practitioner-controlled intermittent treatment strategies.. The mean total costs, but not the mean direct medical costs, were higher in general practitioner-controlled intermittent treatment strategies with esomeprazole compared with a patient-controlled on-demand treatment strategy.

Topics: Anti-Ulcer Agents; Cost-Benefit Analysis; Drug Costs; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Long-Term Care; Male; Middle Aged; Patient Satisfaction; Treatment Outcome

Proton pump inhibitors are regarded as the most effective class of acid suppressive medication for gastroesophageal reflux disease treatment. There is considerable interest regarding the dose equivalence between various proton pump inhibitors.. To compare the efficacy of pantoprazole and esomeprazole with regard to healing and relief from gastroesophageal reflux disease-related symptoms.. Multicenter, randomized, double-blind study. Patients with gastroesophageal reflux disease grades B/C (Los Angeles classification) received 40 mg pantoprazole daily (n = 113) or 40 mg esomeprazole daily (n = 114). Healing (endoscopy) and relief from gastroesophageal reflux disease-related symptoms (direct questioning) were assessed at first and final visit (after 4, 6, 8, or 10 weeks of treatment).. Overall healing in both treatment groups was 88% of patients (intention-to-treat population), 95% (pantoprazole), and 90% (esomeprazole) (per-protocol population); statistically, this indicates "at least equivalence" between treatments. Overall relief from gastroesophageal reflux disease-related symptoms was similar for pantoprazole (55%) and esomeprazole (51%, per-protoco). No correlation between healing and symptom relief was seen. The majority of reported adverse events were assessed as "not related" to the study drug. Pantoprazole and esomeprazole have comparably good safety and tolerability.. In patients with gastroesophageal reflux disease, 40 mg pantoprazole daily and 40 mg esomeprazole daily are equally effective for healing of esophageal lesions and relieving gastroesophageal reflux disease-related symptoms.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Benzimidazoles; Double-Blind Method; Endoscopes, Gastrointestinal; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Pantoprazole; Sulfoxides; Treatment Outcome; Upper Gastrointestinal Tract

Patients with refractory gastro-oesophageal reflux disease, extra-oesophageal reflux symptoms, Barrett's oesophagus, or Zollinger-Ellison syndrome may require greater acid suppression than that obtained with once-daily esomeprazole.. To assess gastric acid suppression (determined by intragastric pH) and pharmacokinetics of twice-daily vs. once-daily esomeprazole.. In a randomized, double-blind, three-way crossover study, healthy subjects received esomeprazole 40 mg once daily, 20 mg twice daily, or 40 mg twice daily for five consecutive days. Twenty-four-hour continuous ambulatory intragastric pH was recorded on day 5.. Esomeprazole 40 mg twice daily provided a mean of 19.2 h with intragastric pH > 4.0 (80.1% of a 24-h time period; 95% confidence interval 74.5-85.7%) vs. 14.2 h with 40 mg once daily (59.2%; 95% CI 53.7-64.7%) and 17.5 h with 20 mg twice daily (73.0%; 95% confidence interval 67.4-78.5%) in 25 subjects. Intragastric pH was maintained >4.0 for a similar percentage of time during active and sleeping periods for all doses.. Esomeprazole 40 mg twice daily provides significantly greater acid suppression (number of hours in a 24-h period with pH > 4.0) than once-daily dosing and may be a reasonable consideration for patients requiring greater acid suppression for acid-related disease.

Topics: Adult; Anti-Ulcer Agents; Cross-Over Studies; Double-Blind Method; Esomeprazole; Female; Gastric Acid; Gastroesophageal Reflux; Humans; Male

Patients with endoscopy-negative reflux disease have reflux symptoms, mainly heartburn, but not mucosal breaks characteristic of erosive oesophagitis. Standard-dose proton pump inhibitors can provide symptom relief in endoscopy-negative reflux disease but the effect of greater acid suppression has not been studied.. To test the hypothesis that esomeprazole produces heartburn resolution in a greater proportion of patients with ENRD than omeprazole.. Three multi-centre randomized, controlled, double-blind, 4-week acute treatment studies were conducted in endoscopy-negative reflux disease patients. In study A (n = 1282), patients received either esomeprazole 40 mg, esomeprazole 20 mg or omeprazole 20 mg daily; in studies B (n = 693) and C (n = 670) patients received either esomeprazole 40 mg or omeprazole 20 mg (B), and esomeprazole 20 mg or omeprazole 20 mg (C), respectively.. Resolution of heartburn at 4 weeks (no heartburn symptoms during the last 7 days) was achieved in similar proportions of patients in each treatment arm in study A (esomeprazole 40 mg, 56.7%; esomeprazole 20 mg, 60.5%; omeprazole 20 mg, 58.1%), study B (esomeprazole 40 mg, 70.3%; omeprazole 20 mg, 67.9%) and study C (esomeprazole 20 mg, 61.9%; omeprazole 20 mg, 59.6%). There were no significant differences between treatment groups within each study.. More than 60% of endoscopy-negative reflux disease patients reported heartburn resolution but, after 4 weeks of therapy, these proportions did not differ significantly between treatments.

Topics: Adult; Aged; Anti-Ulcer Agents; Esomeprazole; Female; Gastric Acid; Gastroesophageal Reflux; Gastroscopy; Humans; Male; Middle Aged; Omeprazole; Treatment Outcome

To compare the effect of esomeprazole 40 mg with lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg on intragastric pH during single and repeated dosing in four separate studies in patients with symptoms of gastro-oesophageal reflux disorder (GERD).. In four randomised crossover studies, patients with symptoms of GERD received once-daily treatment with esomeprazole 40 mg or lansoprazole 30 mg (study A), omeprazole 20 mg (study B), pantoprazole 40 mg (study C) and rabeprazole 20 mg (study D) for 5 days. Continuous 24-h intragastric pH recording was performed on days 1 (except study B) and 5. Percentage of time over 24 h with intragastric pH greater than 4, 24-h median pH and the proportion of patients with pH greater than 4 for greater than or equal to 12 h and 16 h during the 24-h recording periods were investigated.. In all four studies, esomeprazole 40 mg OD maintained intragastric pH greater than 4 for a significantly higher mean percentage of the 24-h period compared with all other proton pump inhibitors (PPIs) on days 1 (esomeprazole 40.6% versus lansoprazole 33.4%, P=0.0182; esomeprazole 50.3% versus pantoprazole 29.1%, P<0.001; esomeprazole 41.0% versus rabeprazole 29.4%, P=0.002) and 5 (esomeprazole 57.7% versus lansoprazole 44.5%, P<0.0001; esomeprazole 69.8% versus omeprazole 43.7%, P<0.0001; esomeprazole 67.0% versus pantoprazole 44.8%, P<0.001; esomeprazole 59.4% versus rabeprazole 44.5%, P<0.0001). Higher 24-h median pH and a higher proportion of patients with intragastric pH greater than 4 for greater than or equal to 12 h and 16 h were reported with esomeprazole 40 mg OD than with all the other PPIs in each study.. Esomeprazole 40 mg provides greater acid control in more patients and maintains intragastric pH greater than 4 for a longer period than lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg in patients with symptoms of GERD.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adult; Anti-Ulcer Agents; Benzimidazoles; Cross-Over Studies; Esomeprazole; Female; Gastric Acid; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Middle Aged; Omeprazole; Pantoprazole; Rabeprazole; Sulfoxides; Treatment Outcome

Symptom relief, through adherence to appropriate maintenance therapy, is the sole objective of treatment for patients with endoscopy-negative gastro-oesophageal reflux disease.. To compare the efficacy of 'on-demand' treatment with esomeprazole 20 mg vs. continuous treatment with lansoprazole 15 mg daily in patients with endoscopy-negative gastro-oesophageal reflux disease.. Endoscopy-negative gastro-oesophageal reflux disease patients who achieved complete resolution of heartburn after short-term (2-4 weeks) treatment with esomeprazole 20 mg (n = 774) were randomized to receive either esomeprazole 20 mg on-demand (n =311) or lansoprazole 15 mg continuous daily treatment (n = 311) for 6 months.. Significantly more patients were willing to continue taking esomeprazole on-demand than lansoprazole continuous therapy after 6 months (93% vs. 88%; P = 0.02). This superior outcome was achieved despite patients on esomeprazole requiring medication only 38% as often as those on lansoprazole, leading to direct cost savings of more than one-third (36%). Furthermore, patients receiving esomeprazole 20 mg on-demand were more satisfied with their treatment after 1 month compared with patients taking lansoprazole 15 mg continuously.. In patients with endoscopy-negative gastro-oesophageal reflux disease, esomeprazole 20 mg on-demand is more acceptable to patients and is an economically more effective treatment than lansoprazole 15 mg continuously.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Esomeprazole; Gastroesophageal Reflux; Humans; Lansoprazole; Middle Aged; Patient Satisfaction; Single-Blind Method; Treatment Outcome

There is little information on the prevalence of pathological sleep disorders in patients with gastro-oesophageal reflux disease and whether pharmacological treatment of patients with gastro-oesophageal reflux disease will lead to improvement in sleep.. This pilot study determined the prevalence of sleep disorder in patients with erosive gastro-oesophageal reflux disease, correlated subjective (questionnaire) and objective (actigraphy - a watch worn on the wrist that monitors motion to help differentiate sleep from awake states) assessment of sleep dysfunction and determined whether therapeutic resolution of oesophageal symptoms was associated with an improvement in sleep.. Eighteen patients with erosive gastro-oesophageal reflux disease received esomeprazole 40 mg once daily for 8 weeks. Assessments at 0, 4 and 8 weeks included: Gastrointestinal Symptoms Rating Scale, Pittsburgh Sleep Quality Index questionnaire and ambulatory wrist actigraphy.. Unrecognized sleep disturbance occurred in 81% of this cohort of patients with gastro-oesophageal reflux disease and erosive oesophagitis. Median reflux syndrome score (heartburn and acid regurgitation) on Gastrointestinal Symptoms Rating Scale decreased from 2 at baseline to 0 at weeks 4 and 8 (P

Topics: Anti-Ulcer Agents; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pilot Projects; Sleep Wake Disorders; Treatment Outcome

To compare the efficacy of esomeprazole, 20 mg once daily, vs. lansoprazole, 15 mg once daily, for the maintenance treatment of patients with healed reflux oesophagitis.. During the initial open healing phase, 1391 patients with endoscopically verified reflux oesophagitis and a history of heartburn, with or without acid regurgitation, received esomeprazole 40 mg for 4-8 weeks. Patients who were healed (identified by endoscopy at 4 or 8 weeks) and symptom free were then randomized to receive 6 months of treatment with esomeprazole, 20 mg once daily, or lansoprazole, 15 mg once daily.. Esomeprazole, 20 mg once daily, maintained a significantly higher proportion of patients in remission than lansoprazole, 15 mg once daily, over 6 months [83% (95% CI, 80-86%) of esomeprazole recipients compared with 74% (95% CI, 70-78%) of lansoprazole recipients; P < 0.0001; life table estimates]. When data were analysed according to baseline Los Angeles grade classification, esomeprazole, 20 mg once daily, achieved consistently higher remission rates across all grades of disease severity, whereas the efficacy of lansoprazole decreased to a greater extent with increasing severity of reflux oesophagitis.. Esomeprazole, 20 mg once daily, is more effective than lansoprazole, 15 mg once daily, in maintaining remission in patients with healed reflux oesophagitis.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Double-Blind Method; Esomeprazole; Esophagitis; Female; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Recurrence; Survival Analysis; Treatment Outcome

Objectives were to determine the efficacy of empiric treatment with esomeprazole for patients diagnosed with laryngopharyngeal reflux and to determine a treatment paradigm for this patient population.. Prospective study.. Patients were treated with a once-daily dose of 40 mg esomeprazole for 8 weeks. All patients completed a subjective symptom scale (rating laryngeal symptoms and esophageal symptoms) and scoring of flexible fiberoptic examination before treatment and at 4 and 8 weeks of treatment. Nonresponders (<50% reduction in symptom score) were recommended to undergo 24-hour dual-probe pH study while on a regimen of 40 mg esomeprazole once a day, to evaluate for the adequacy of acid suppression.. Thirty patients completed the course of therapy. After 4 weeks of treatment, only 8 of 30 patients had significant improvement of their overall symptoms (8 of 30 improved on laryngeal score, and 11 of 18 improved on esophageal score). At 8 weeks of treatment, 19 of 30 patients had significant improvement on their overall symptoms (18 of 30 on laryngeal score, and 13 of 18 on their esophageal score). Five of seven nonresponders who agreed to be tested had positive findings on pH studies (on medication regimen) at 1 cm above the upper esophageal sphincter. Four of 10 nonresponders improved further after increasing their dosage to 40 mg twice a day. Laryngeal examination scores were statistically improved in responders after 8 weeks of treatment.. Laryngopharyngeal reflux symptoms require at least 8 weeks of treatment for significant improvement in the majority of patients. Esophageal symptoms improve sooner. Nonresponders at a daily dose of 40 mg should be treated with a dosage of 40 mg twice daily, and pH study on medication reserved for nonresponders at this higher dose. Laryngeal examination scores showed mild but statistically significant improvement at 8 weeks of therapy in responders.

Topics: Anti-Ulcer Agents; Drug Administration Schedule; Esomeprazole; Fiber Optic Technology; Follow-Up Studies; Gastroesophageal Reflux; Humans; Laryngeal Diseases; Pharyngeal Diseases; Prospective Studies; Severity of Illness Index; Treatment Outcome

To assess symptom relief in patients with heartburn following treatment with esomeprazole 40 mg daily.. Patients with heartburn (for > or = 6 months) were assessed in this double-blind, multicenter study. After a 3-day single-blind placebo run-in, 440 patients were randomized to esomeprazole 40 mg o.d., esomeprazole 20 mg b.i.d. or placebo for 14 days. Heartburn symptoms were recorded daily; as insufficient patients had data available from days 13 and 14, analyses included data up to day 12. Gastroesophageal reflux disease (GERD) was diagnosed by upper GI endoscopy and 24-h pH-monitoring. The primary end-point was total heartburn relief defined as no heartburn symptoms during the preceding 24-h period.. 240 patients had erosive esophagitis (EO) and 114 patients had GERD defined by pH-monitoring. Proportions of patients with total heartburn relief increased during the first days of treatment and stabilized after Day 4. Total heartburn relief occurred in 67%-73%, 62%-70%, and 21%-32% of patients in the esomeprazole 40 mg o.d., esomeprazole 20 mg b.i.d., and placebo groups, respectively, between days 6 and 12. Proportions of patients with total heartburn relief were higher in patients with EO (71%-80% of patients from Day 4 onwards) compared to those without EO (52%-67% of patients from Day 4 onwards). Figures for patients diagnosed by pH-monitoring were 65%-73% of those with a positive diagnosis and 51%-58% with a negative diagnosis.. Esomeprazole 40 mg o.d. treatment produces total heartburn relief in a high proportion of patients with GERD. Once-daily esomeprazole 40 mg dosing is recommended as no advantage was gained by splitting the dose.

Topics: Adult; Aged; Anti-Ulcer Agents; Double-Blind Method; Endoscopy, Gastrointestinal; Esomeprazole; Female; Gastric Acidity Determination; Gastroesophageal Reflux; Heartburn; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Prospective Studies; Treatment Outcome

Symptomatic response to acid inhibition can be used as a guide in diagnosing patients with reflux symptoms. The proton-pump inhibitor (PPI) omeprazole has been used as such a diagnostic tool. Intragastric acid control with esomeprazole is more effective than other PPIs and has the potential to offer an advance in the diagnostic use of PPIs.. Patients experiencing heartburn (for > or = 6 months) were studied in this randomized, double-blind, multicenter study. Following a 3-day placebo run-in, 440 patients were randomized to 14 days' treatment with esomeprazole 40 mg once daily (o.d.), esomeprazole 20 mg twice daily (b.i.d.) or placebo. Heartburn symptoms were recorded daily. Endoscopy and 24-h esophageal pH-monitoring were performed to determine the presence of gastroesophageal reflux disease (GERD). The esomeprazole treatment test was considered positive if patients' symptoms improved during the treatment period compared with symptoms recorded on Day 0.. 63 patients were excluded from the analysis due to lack of symptoms on Day 0 or failure to complete pH-monitoring. The sensitivity of an esomeprazole treatment test in confirming GERD increased during the first days of treatment and stabilized between 79% and 86% after 5 days (both esomeprazole arms). The corresponding figure for the placebo arm was 36%. Specificity was variable (24%-65%) for both active treatment and placebo.. A treatment test with esomeprazole 40 mg has a high sensitivity in confirming GERD. Furthermore, the data indicate that 1-week treatment with a once-daily dosage is sufficient to ensure adequate diagnosis.

Topics: Adult; Aged; Anti-Ulcer Agents; Double-Blind Method; Endoscopy, Gastrointestinal; Esomeprazole; Female; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Omeprazole; Prospective Studies; Proton Pump Inhibitors; Sensitivity and Specificity

To compare the effect of pantoprazole and esomeprazole on intra-oesophageal pH and investigate their pharmacokinetics in patients with symptomatic gastro-oesophageal reflux disease (GORD).. Double-blind, randomized, two-period crossover study. Caucasian men with symptomatic GORD (n=48) were selected on the basis of clinical records of typical GORD symptoms, confirmed by a pathological reflux time (oesophageal pH<4 for > or =6% of the time). They received oral pantoprazole 40 mg once daily (od) or esomeprazole 40 mg od for seven days. Continuous 24 h oesophageal pH-metry was performed at baseline and day 7. Evaluations included: pre- and post-treatment differences in the percentage of time with pH<4.0 and <3.0 between baseline and day 7; area under the curve (AUC), Cmax, and T(1/2); point estimates and 90% confidence intervals (CI) on days 1 and 7, calculated for ratios of the AUC and Cmax.. Both drugs decreased the mean total number of reflux episodes and reduced the percentage of reflux time within 24 h to <3%. No pathological reflux was detectable after repeated administration of either drug. The 90% CI were within the predefined range at all time points; thus, equivalence of pantoprazole and esomeprazole was concluded. For pantoprazole, Cmax and AUC were unchanged on day 7 vs day 1, confirming its high and constant bioavailability. For esomeprazole, Cmax and AUC were increased on day 7 vs day 1 by 80% and 50%, respectively, indicating low initial bioavailability. No clinically relevant side effects were seen for either drug.. Pantoprazole and esomeprazole have equivalent effect on oesophageal pH, since no pathological reflux was detected after treatment with either drug. For esomeprazole, the Cmax and AUC increased after multiple dosing; for pantoprazole the pharmacokinetics were predictable and independent of the number of administered doses.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Benzimidazoles; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Esomeprazole; Esophagus; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Pantoprazole; Sulfoxides

To compare the efficacy of pantoprazole and esomeprazole for the treatment of gastro-oesophageal reflux disease- (GERD-) related symptoms.. In this multicentre, randomized, double-blind study 217 patients [intention-to-treat (ITT) population] diagnosed with endoscopically proven GERD grade B/C received pantoprazole (40 mg once daily (o.d.), n = 112] or esomeprazole (40 mg o.d/, n = 105) for 4 weeks. Patients recorded GERD-related symptoms (daytime and night-time) using diaries (daily), and/or by telephone interviews (every third day) and completed the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. The area under the time curve (AUC) for the sum score of GERD-related symptoms (symptom load of each patient during the treatment) and the time to reach adequate relief from GERD-related symptoms were calculated.. Patients reported first adequate relief from daytime GERD-related symptoms after a mean of 3.7 (pantoprazole) and 5.9 days (esomeprazole) (P = 0.034); the values for the night-time were 1.7 and 3.5 days, respectively (P = 0.012, ITT). The AUCs for the single symptoms and the sum scores were comparable.. Treatment with pantoprazole resulted in significantly faster first-time relief from daytime and night-time GERD-related symptoms than esomeprazole. Pantoprazole and esomeprazole were similar with respect to reduction of load of GERD-related symptoms.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Benzimidazoles; Double-Blind Method; Drug Administration Schedule; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pantoprazole; Sulfoxides; Surveys and Questionnaires; Treatment Outcome

The purpose of this study is a comparative assessment of the clinical efficiency of Omeprazole and Esomeprazole in patients suffering from bronchial asthma (BA) with associated gastroesophageal reflux disease (GERD). 101 patients with BA and associated GERD being under study were divided into three groups depending on the way of application of the anti-reflux therapy. Patients from the I group were administered Omeprazole--20 mg per day, patients from the II group received Omeprazole--mg per day, and patients from the III group were administered Esomeprazole--40 mg per day, the treatment courses of each group amounting to eight weeks. The clinical efficiency indices of pulmonary (CEIP) and esophageal (CEIE) symptoms were calculated when the results of the study were summed. The decrease of CEIP and CEIE against the background of the anti-reflux therapy (for example, the CEIP of patients from the III group decreased from 14.9 +/- 1.5 (before the treatment) to 2.9 +/- 0.6 points following eight weeks of treatment (p < 0.001), and the CEIE decreased from 9.0 +/- 1.2 (before the treatment) to 1.7 +/- 0.3 points following eight weeks of treatment (p < 0.001)) has demonstrated the reliable improvement of the clinical course of BA with associated GERD. We failed to discover any essential differences between the impact of Omeprazole in the dose equal to 40 mg per day and the impact of Esomeprazole in the same dose on the CEIP. Thus, the CEIP amounted to 10.1 +/- 1.2 points in the II group and 8.5 +/- 1.4 points in the III group (p > 0.05) after the fourth week of treatment. At the same time, we have discovered a reliable advantage of Esomeprazole as compared with Omeprazole for the improvement of the CEIE. The therapy of BA with associated GERD with Omeprazole in the dose equal to 40 mg per day or Esomeprazole in the dose equal to 40 mg per day contributes to the reliable improvement of both pulmonary and esophageal symptoms, and application of Esomeprazole results in a faster reduction of bronchial obstruction and gastroesophageal reflux.

Topics: Adult; Anti-Ulcer Agents; Asthma; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Omeprazole; Time Factors; Treatment Outcome

Proton pump inhibitors owe their clinical efficacy to their ability to suppress gastric acid production. The objective of this study was to evaluate and compare intragastric pH following standard doses of esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole.. This randomized, open-label, comparative five-way crossover study evaluated the 24-h intragastric pH profile of oral esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg, and rabeprazole 20 mg once daily in 34 Helicobacter pylori-negative patients aged 18-60 yr with symptoms of gastroesophageal reflux disease. Patients were randomly assigned to one of five treatment sequences and study drug was taken on 5 consecutive mornings 30 minutes prior to a standardized breakfast. A washout period of at least 10 days separated each treatment phase.. Thirty-four patients provided evaluable data for all five comparators. The mean number of hours of evaluable pH data was > or =23.75 hours. On day 5, intragastric pH was maintained above 4.0 for a mean of 14.0 h with esomeprazole, 12.1 h with rabeprazole, 11.8 h with omeprazole, 11.5 h with lansoprazole, and 10.1 h with pantoprazole (p < or = 0.001 for differences between esomeprazole and all other comparators). Esomeprazole also provided a significantly higher percentage of patients with an intragastric pH greater than 4.0 for more than 12 h relative to the other proton pump inhibitors (p < 0.05). The frequency of adverse events was similar between treatment groups.. Esomeprazole at the standard dose of 40 mg once daily provided more effective control of gastric acid at steady state than standard doses of lansoprazole, omeprazole, pantoprazole, and rabeprazole in patients with symptoms of gastroesophageal reflux disease.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Anti-Ulcer Agents; Benzimidazoles; Chi-Square Distribution; Cross-Over Studies; Esomeprazole; Female; Gastric Acid; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Lansoprazole; Least-Squares Analysis; Male; Middle Aged; Omeprazole; Pantoprazole; Rabeprazole; Sulfoxides; Treatment Outcome

To compare the effects of standard-dose esomeprazole with those of standard doses of lansoprazole and rabeprazole on intragastric pH during repeated daily oral dosing in healthy volunteers.. In two standardized, randomized crossover studies, Helicobacter pylori negative healthy volunteers (study A: 19 males, 5 females; study B: 13 males, 10 females) received esomeprazole 40 mg and either lansoprazole 30 mg (study A) or rabeprazole 20 mg (study B) orally once daily in the morning for 5 days. Continuous 24-hour intragastric pH recording was performed on day 5.. The intragastric pH was maintained >4 for 65% (95% CI 59.5-71.3) of the 24-hour period with esomeprazole and for 53% of the time (95% CI 47.0-58.9) with lansoprazole in study A (p < 0.001). In study B, the proportion of time with pH >4 was 61% (95% CI 53.6-68.3) with esomeprazole versus 45% (95% CI 37.7-52.5) with rabeprazole (p = 0.005). The 24-hour median pH and the proportion of volunteers with intragastric pH >4 for > or =12 h and > or =16 h were significantly higher with esomeprazole than with either lansoprazole or rabeprazole.. Esomeprazole 40 mg provides significantly more effective and more sustained gastric acid control than lansoprazole 30 mg or rabeprazole 20 mg in healthy volunteers.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adult; Anti-Ulcer Agents; Benzimidazoles; Cross-Over Studies; Esomeprazole; Female; Gastric Acid; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Middle Aged; Rabeprazole

To compare antisecretory effects of Rabeprazole and Esomeprazole in proton pump inhibitors extensive metabolizers in an open, randomized, two-way crossover study.. Sixteen GERD H. pylori-positive patients (8 men, mean age 49.6 and 8 women, mean age 49.3) with the homozygous extensive metabolizer genotype of CYP2C19 determined by polymerase chain reaction-restriction fragment length polymorphism analysis received Rabeprazole 20 mg or Esomeprazole 20 mg daily on days 1-6, with a 14-day wash-out period. Intragastric pH was recorded continuously on days 0, 1, 5 and 7.. On days 1 and 5 no differences were found between Rabeprazole 20 mg and Esomeprazole 20 mg in 24-hours median pH (day 1: 5.9 versus 5.0; day 5: 6.45 versus 6.3) or in percent of time with pH 4 (day 1: 57.8% versus 50.5%; day 5: 81.4% versus 81.2%). On day 1, mean percent of time pH 4 were significantly greater after Esomeprazole 20 mg 52.6% (95% CI: 23.6-68.2) than Rabeprazole 20 mg 33.0% (95% CI: 15.3-48.2) during 0-6 h (p = 0.02). On day 7 (24 later the last dose), 24-hours median pH was higher after Esomeprazole 20 mg than Rabeprazole 20 mg (2.7 versus 5.05; p = 0.02).. Rabeprazole 20 mg and Esomeprazole 20 mg are equally effective in increasing gastric pH in H. pylori-positive PPI extensive metabolizers on days 1 and 5. Esomeprazole 20 mg is more effective than Rabeprazole 20 mg in maintaining pH 4 during the first 6 hours on the first day and increasing of intragastric pH on the day 24 hours later the last dose.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Aryl Hydrocarbon Hydroxylases; Benzimidazoles; Cross-Over Studies; Cytochrome P-450 CYP2C19; Esomeprazole; Female; Gastric Acid; Gastric Acidity Determination; Gastroesophageal Reflux; Genotype; Humans; Inactivation, Metabolic; Male; Middle Aged; Mixed Function Oxygenases; Polymorphism, Genetic; Proton Pump Inhibitors; Rabeprazole; Treatment Outcome

On-demand therapy may offer an effective approach to the long-term management of gastro-oesophageal reflux disease (GORD) without oesophagitis.. To examine the efficacy of the novel proton pump inhibitor esomeprazole as on-demand therapy in endoscopy-negative GORD.. Endoscopy-negative GORD patients who achieved complete resolution of heartburn after short-term esomeprazole or omeprazole treatment (n = 721) were randomized to esomeprazole 20 mg (n = 282), 40 mg (n = 293) or placebo (n = 146) on demand (maximum one dose/day) for 6 months. The primary and secondary efficacy endpoints were time to study discontinuation due to (i) unwillingness to continue and (ii) inadequate control of heartburn, respectively.. Both doses of esomeprazole were more effective than placebo. During the 6-month period, 42% of placebo recipients discontinued treatment due to unwillingness to continue, compared with 8% and 11% of esomeprazole 20 mg and 40 mg recipients, respectively. Overall, more patients treated with esomeprazole were free from gastrointestinal symptoms after 6 months of on-demand therapy.. Esomeprazole 20 mg was superior to placebo for on-demand treatment of GORD; a higher dose did not confer additional clinical benefit. Over 90% of patients were willing to continue on-demand treatment with esomeprazole 20 mg over a 6-month period.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Esomeprazole; Esophagoscopy; Female; Follow-Up Studies; Gastroesophageal Reflux; Gastroscopy; Humans; Long-Term Care; Male; Middle Aged; Omeprazole; Patient Satisfaction; Probability; Reference Values; Severity of Illness Index; Treatment Outcome

Maintenance of intragastric pH > 4 is vital for effective management of gastroesophageal reflux disease (GERD). Esomeprazole 40 mg, the first proton pump inhibitor developed as an optical isomer, demonstrates improved acid inhibition over omeprazole 20 mg. Our aim was to compare esomeprazole 40 mg with omeprazole 40 mg, once-daily, on intragastric acidity in patients with symptoms of GERD. In this open-label, crossover study, 130 patients with symptoms of GERD received esomeprazole 40 mg or omeprazole 40 mg once-daily for five days. The 24-hr intragastric pH was monitored on days 1 and 5 of each treatment period. The mean percentage of the 24-hr period with intragastric pH > 4 was significantly greater (P < 0.001) with esomeprazole 40 mg than with omeprazole 40 mg on days 1 (48.6% vs 40.6%) and 5 (68.4% vs 62.0%). Interpatient variability was significantly less with esomeprazole than omeprazole. Esomeprazole was well tolerated. In conclusion, esomeprazole 40 mg provides more effective acid control than twice the standard dose of omeprazole.

Topics: Adult; Aged; Anti-Ulcer Agents; Cross-Over Studies; Drug Tolerance; Esomeprazole; Female; Gastric Juice; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Omeprazole

Esomeprazole, the S-isomer of omeprazole, achieves a significantly greater healing rate and symptom resolution of erosive esophagitis than that achieved by omeprazole. The objective of this study is to assess the efficacy of the new proton pump inhibitor esomeprazole in preventing relapse over a prolonged period in patients with healed erosive esophagitis.. A total of 318 gastroesophageal reflux patients whose erosive esophagitis was healed in a comparative study of esomeprazole 40 mg, 20 mg, or omeprazole 20 mg, were randomized to maintenance therapy with once daily esomeprazole 40 mg, 20 mg, or 10 mg, or placebo in a U.S., double-blind multicenter trial.. After 6 months, healing was maintained (cumulative life table rates) in 93.6% (95% CI 87.4-99.7) of patients treated with esomeprazole 40 mg, 93.2% (95% CI 87.4-99.0) treated with esomeprazole 20 mg, and 57.1% (95% CI 45.2-69) treated with esomeprazole 10 mg; p < 0.001 vs placebo (29.1%; 95% CI 17.7-40.3). Of patients relapsing, mean time to first recurrence of esophagitis increased with dose, from 34 days (placebo) to 78 days (10 mg), 115 days (20 mg), and 163 days (40 mg). Patients treated with esomeprazole had less frequent and less severe heartburn than those treated with placebo. At month 6, more than 70% of patients being treated with esomeprazole remained symptom-free.. Esomeprazole is effective and well tolerated in the maintenance of a healing erosive esophagitis. Esomeprazole 40 mg and 20 mg maintain healing in over 90% of patients while providing effective control of heartburn symptoms.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Biopsy, Needle; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Enzyme Inhibitors; Esomeprazole; Esophagitis; Female; Follow-Up Studies; Gastric Mucosa; Gastroesophageal Reflux; Humans; Male; Middle Aged; Omeprazole; Probability; Reference Values; Secondary Prevention; Treatment Outcome

Most patients with gastro-oesophageal reflux disease (GERD), regardless of endoscopic status, suffer symptomatic relapse within 6 months of stopping acid suppressant therapy.. To assess the efficacy of 'on-demand' treatment of GERD with esomeprazole, the first proton pump inhibitor developed as an optical isomer.. In this multicentre, double-blind study, 342 endoscopy-negative GERD patients demonstrating complete resolution of heartburn during the final week of a 4-week treatment period with esomeprazole 20 mg or omeprazole 20 mg once daily were randomized to receive esomeprazole 20 mg or placebo on demand (maximum of one dose per day) for a further 6 months. Use of rescue antacids was permitted.. All 342 patients (191 males), aged 19-79 (mean 49) years, were evaluable in the intention-to-treat analysis. The proportion of patients who discontinued treatment due to insufficient control of heartburn was significantly higher among placebo compared to esomeprazole recipients (51% vs. 14%; P < 0.0001). Patients randomized to esomeprazole on-demand therapy remained in the study longer than those in the placebo group (mean 165 vs. 119 days). Over 50% took the study medication for periods of 1--3 consecutive days (esomeprazole) or 4--13 consecutive days (placebo). Use of antacids was > 2-fold higher among placebo recipients. The frequency of adverse events was similar in the two groups, when adjusted for time spent in the study, as were the clinical laboratory profiles.. On-demand therapy with esomeprazole 20 mg is effective and well tolerated in maintaining symptom control in endoscopy-negative GERD.

Topics: Administration, Oral; Adult; Aged; Anti-Ulcer Agents; Double-Blind Method; Drug Administration Schedule; Endoscopy; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Omeprazole; Patient Satisfaction; Proton Pump Inhibitors; Stereoisomerism; Treatment Outcome

In patients with gastroesophageal reflux disease (GERD), esomeprazole, the S-isomer of omeprazole, has demonstrated pharmacological and clinical benefits beyond those seen with the racemic parent compound. This study was designed to further evaluate the efficacy and tolerability of esomeprazole relative to that of omeprazole in healing erosive esophagitis and resolving accompanying symptoms of GERD.. Esomeprazole 40 mg was compared with omeprazole 20 mg once daily in 2425 patients with erosive esophagitis (Helicobacter pylori negative by serology) in an 8-wk, multicenter, randomized, double-blind, parallel-group study conducted in 163 centers throughout the US. The primary efficacy endpoint was the proportion of patients with healed esophagitis at wk 8. Secondary endpoints were the proportion of patients healed at wk 4, resolution of heartburn at wk 4, time to first resolution and sustained resolution of heartburn, and proportion of heartburn-free days and nights. Safety and tolerability were also assessed.. Significantly more patients were healed with esomeprazole versus omeprazole at wk 8 (93.7% vs 84.2%, p < 0.001; life table estimates, intention-to-treat analysis). Healing rates at wk 4 were 81.7% and 68.7%, respectively. Esomeprazole was superior to omeprazole for all secondary measures and had a similar safety profile. The most common adverse events in both treatment groups were headache, diarrhea, and nausea.. Esomeprazole demonstrates significantly greater efficacy than omeprazole in the treatment of GERD patients with erosive esophagitis. The tolerability and safety of esomeprazole are comparable to that of omeprazole. (Am

Topics: Adult; Aged; Double-Blind Method; Enzyme Inhibitors; Esomeprazole; Esophagitis; Female; Gastroesophageal Reflux; Humans; Isomerism; Male; Middle Aged; Omeprazole; Safety; Treatment Outcome

Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor to be developed as an optical isomer. In patients with erosive oesophagitis, esomeprazole has produced significantly greater healing rates and improved symptom resolution vs. omeprazole.. This study assesses the efficacy of esomeprazole for preventing relapse in patients with healed oesophagitis.. In this 6-month US multicentre randomized double-blind placebo-controlled trial, 375 Helicobacter pylori-negative patients with endoscopically healed oesophagitis received esomeprazole 40 mg, 20 mg, 10 mg, or placebo once daily. The primary efficacy end-point was maintenance of healing at 6 months. Secondary end-points assessed changes in symptoms, and long-term safety and tolerability.. Significantly (P < 0.001) more patients remained healed with esomeprazole 40 mg (87.9%), 20 mg (78.7%), or 10 mg (54.2%), than with placebo (29.1%). Relapse, when it occurred, was later with esomeprazole. Sustained resolution of heartburn was observed in the 40 mg and 20 mg groups; there was a high correlation between absence of heartburn and maintenance of healing. Adverse effects were mild, infrequent and not significantly different between groups.. Esomeprazole is effective and well-tolerated in the maintenance of healing of erosive oesophagitis. Esomeprazole 40 mg and 20 mg offer significant clinical benefit to patients.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Double-Blind Method; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Heartburn; Humans; Isomerism; Male; Middle Aged; Placebos; Proton Pump Inhibitors; Recurrence; Treatment Outcome

Esomeprazole (Nexium) is a new proton pump inhibitor for the treatment of acid-related diseases.. In this double-blind crossover study, 38 patients with gastro-oesophageal reflux disease (GERD) symptoms were randomized to esomeprazole 40 and 20 mg and omeprazole 20 mg once daily for 5 days. On day 5 of each dosing period, 24-h intragastric pH and pharmacokinetic variables were measured.. Thirty-six patients aged 29-58 (mean 45) years completed the study. Esomeprazole 40 and 20 mg maintained intragastric pH > 4 for (mean) 16.8 and 12.7 h, respectively, vs. 10.5 h for omeprazole 20 mg (P < 0.001 and P < 0. 01). Twenty-four-hour median intragastric pH was significantly higher with esomeprazole 40 mg (4.9) and 20 mg (4.1) than with omeprazole 20 mg (3.6) (P < 0.001 and P < 0.01). Area under the plasma concentration-time curve (AUC) was 80% higher for esomeprazole 20 mg vs. omeprazole, while that for esomeprazole 40 mg was more than five times higher (each P < 0.0001). Interpatient variability in intragastric pH and AUC was less with esomeprazole than with omeprazole. Esomeprazole was well tolerated and there were no safety concerns.. Esomeprazole provides more effective acid control than omeprazole, with reduced interpatient variability, thereby offering the potential for improved efficacy in acid-related diseases.

Topics: Adult; Anti-Ulcer Agents; Cross-Over Studies; Double-Blind Method; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Omeprazole; Stereoisomerism

The aim was to examine actual health care cost in patients with gastroesophageal reflux disease (GERD) who were initiated on proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) as first-line therapy in Japanese real-world clinical settings.. To date, cost-utility evaluation of acid-suppressants treatment in Japan has only been conducted by model analysis.. A cost utilization analysis was performed using a Japanese nationwide hospital-based claim database by extracting patients with GERD initiated on either PPI or P-CAB (242,102 pairs) and esomeprazole (EPZ) or P-CAB (241,825 pairs). Health care costs were compared in each comparison cohort with propensity-score matched pairs. The switching rates of initial acid-suppressants were also examined.. Baseline characteristics were well-balanced after matching. The 3-year mean cumulative GERD-related and hospitalization costs per patient were ¥142,620 and ¥122,444 in PPI-first and P-CAB-first treatment groups, and ¥105,263 and ¥121,958 in EPZ-first and P-CAB-first treatment groups, respectively. Most hospitalization costs were non-GERD related in all the groups. The switching rates of PPI to P-CAB and P-CAB to PPI in 12 months were 7.5% and 20.2%, respectively.. In this propensity-score matched analysis, health care cost was higher in patients with GERD initiated on PPI than in those initiated on P-CAB mainly owing to non-GERD-related hospitalization cost, whereas it was lower in those initiated on EPZ than in those initiated on P-CAB. When considering health care costs except hospitalization costs, PPI-first treatment was less expensive than P-CAB-first treatment. Low switching rate from PPI to P-CAB in the real-world practice may partially explain the discrepancy.

Topics: Esomeprazole; Gastroesophageal Reflux; Health Care Costs; Humans; Personality; Proton Pump Inhibitors; Treatment Outcome

Topics: Dexlansoprazole; Esomeprazole; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors

Side effects of proton pump inhibitors (PPI) can be linked to the changes in the intestinal microbiome that occur during therapy, especially in long-term users. Therefore, the microbiome might also be a key player in the reduction of PPI side effects. We tested the effects of a three-month intervention with a multispecies synbiotic on intestinal inflammation, gut barrier function, microbiome composition, routine laboratory parameters and quality of life in patients with long-term PPI therapy. Thirty-six patients received a daily dose of a multispecies synbiotic for three months and were clinically observed without intervention for another three months. After intervention 17% of patients reached normal calprotectin levels; the overall reduction did not reach statistical significance (-18.8 ng/mg; 95%CI: -50.5; 12.9, p = 0.2). Elevated zonulin levels could be significantly reduced (-46.3 ng/mg; 95%CI: -71.4; -21.2; p < 0.001). The abundance of Stomatobaculum in the microbiome was reduced and Bacillus increased during the intervention. Furthermore, albumin, alkaline phosphatase and thrombocyte count were significantly increased and aspartate transaminase was significantly decreased during intervention. Gastrointestinal quality of life showed significant improvements. In conclusion, microbiome-related side effects of long-term PPI use can be substantially reduced by synbiotic intervention. Further studies are warranted to optimize dosage and duration of the intervention.

Topics: Aged; Alkaline Phosphatase; Anti-Ulcer Agents; Aspartate Aminotransferases; Bacillus; Clostridiales; Dysbiosis; Esomeprazole; Female; Gastroesophageal Reflux; Gastrointestinal Microbiome; Gene Expression Regulation; Haptoglobins; Humans; Lactobacillus; Lactococcus; Leukocyte L1 Antigen Complex; Male; Middle Aged; Pantoprazole; Peptic Ulcer; Pilot Projects; Prebiotics; Probiotics; Protein Precursors; Proton Pump Inhibitors; Quality of Life

Gastroesophageal reflux disease (GERD) can be treated using a vonoprazan-first strategy (first-line treatment with vonoprazan), or esomeprazole-first/rabeprazole-first strategies (first-line treatment with proton-pump inhibitors [PPIs], esomeprazole/rabeprazole, followed by a switch to vonoprazan). This cost-utility analysis used long-term simulation modeling to evaluate the cost-effectiveness of a vonoprazan-first strategy compared with the esomeprazole-first and rabeprazole-first strategies.. A Markov simulation model was developed to evaluate the cost-effectiveness of vonoprazan-first, esomeprazole-first, and rabeprazole-first strategies, comprising healing and maintenance therapies, over 5 years (4-week cycles). Healing therapy began with the administration of a normal dose of drug per real-world practice. If patients were not healed endoscopically, either a longer duration of healing therapy was provided (vonoprazan), the dose was increased (rabeprazole), or patients were switched to vonoprazan (immediately for esomeprazole, and after dose-escalation for rabeprazole, respectively). Healed patients received maintenance (lower/same dose as healing therapy). Recurrence resulted in re-challenge with healing therapy. Transition probabilities were derived from the results of indirect comparisons (network meta-analysis) and costs calculated from the Japanese payer perspective. Outcomes were defined as quality-adjusted life years (QALYs), with utilities based on published values.. Expected costs of the vonoprazan-, esomeprazole-, and rabeprazole-first strategies were ¥36,194, ¥76,719, and ¥41,105, respectively, over 5 years. QALY gains for vonoprazan-first strategy versus the esomeprazole- and rabeprazole-first strategies were 0.014 and 0.003, respectively. Both estimated incremental cost-effectiveness ratios were dominant and robust to two sensitivity analyses.. Vonoprazan-first strategy increased QALYs and appeared to be cost-effective for GERD patients compared with the esomeprazole- or rabeprazole-first strategies.

Topics: Computer Simulation; Cost-Benefit Analysis; Esomeprazole; Gastroesophageal Reflux; Humans; Japan; Markov Chains; Proton Pump Inhibitors; Pyrroles; Quality-Adjusted Life Years; Rabeprazole; Recurrence; Sulfonamides; Time Factors; Treatment Outcome

Topics: Aged; Drug Eruptions; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors

Empirical proton pump inhibitor (PPI) treatment is recommended as a diagnostic indicator for gastroesophageal reflux disease (GERD) and as a therapy for symptomatic control, with responses generally seen within 4 weeks. However, there are no real-world data assessing the effectiveness of short-term empirical treatment with PPIs in patients with GERD in China.. The ENLIGHT study was a multicenter, prospective, observational study conducted in China. The primary outcome was the overall response rate after 4 weeks' empirical treatment with PPIs. Adult patients aged between 18 and 65 years of age, with a gastroesophageal reflux disease questionnaire score of ≥ 8, prescribed empirical PPI treatment by their physicians and with no planned endoscopy were eligible to participate. Statistical analyses were primarily descriptive.. Overall, 987 patients were eligible to participate and were included in the full analysis set (FAS); 707 patients were included in the per protocol set. In the FAS, esomeprazole was received by 57.1% of patients and was the most commonly used PPI. After 4-week treatment, 71.1% (95% confidence interval [CI], 67.9% to 74.2%) of patients were considered responders to PPI. The response rate at the end of 2-week PPI treatment reached 57.0% (95% CI, 52.5% to 61.7%). The median time to response was 13 days (95% CI, 12 to 15). Response rates at 2 and 4 weeks of the per protocol set were similar to those of the FAS.. Short-term empirical PPI treatment can provide an effective relief of GERD symptoms in most Chinese patients in real-world practice.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Asian People; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Outpatients; Pantoprazole; Prospective Studies; Proton Pump Inhibitors; Rabeprazole; Time Factors; Treatment Outcome; Young Adult

This trial was designed to assess the prevalence and characteristics of Jackhammer esophagus (JE), a novel hypercontractile disorder associated with progression to achalasia and limited outcomes following anti-reflux surgery in patients with typical symptoms of GERD and responsiveness to proton pump inhibitor (PPI) therapy. Consecutive patients, who were referred for surgical therapy because of PPI responsive typical symptoms of GERD, were prospectively assessed between January 2014 and May 2017. Patients diagnosed with JE subsequently underwent rigorous clinical screening including esophagogastroduodenoscopy (EGD), ambulatory pH impedance monitoring off PPI and a PPI trial. Out of 2443 evaluated patients, 37 (1.5%) subjects with a median age of 56.3 (51.6; 65) years were diagnosed with JE and left for final analysis. Extensive testing resulted in 16 (43.2%) GERD positive patients and 5 (13.9%) participants were observed to have an acid hypersensitive esophagus. There were no clinical parameters that differentiated phenotypes of JE. The prevalence of JE in patients with typical symptoms of GERD and response to PPI therapy is low. True GERD was diagnosed in less than half of this selected cohort, indicating the need for objective testing to stratify phenotypes of JE. (NCT03347903).

Topics: Aged; Endoscopy, Digestive System; Esomeprazole; Esophageal Motility Disorders; Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Humans; Male; Manometry; Middle Aged; Prevalence; Proton Pump Inhibitors; Treatment Outcome

The real size of the gastro-oesophageal reflux disease (GERD) population not responding to proton pump inhibitor (PPI) therapy has still not been fully elucidated. Causes of PPI refractoriness include incorrect diagnosis and lack of adherence to therapy, in terms of incorrect dosage and timing.. To evaluate the prevalence of refractoriness to optimal PPI therapy and the contribution of non-erosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn, to PPI refractoriness. The association of functional GI symptoms in non-responders was evaluated.. Frequency and severity of GERD symptoms (heartburn, regurgitation, chest pain), dysphagia, belching, epigastric pain, postprandial distress, irritable bowel syndrome (IBS), globus, and ear nose and throat (ENT) symptoms were evaluated in patients previously classified as non-responders. Patients with at least one of the oesophageal symptoms with a frequency ≥3 /week were treated with esomeprazole 40 mg once daily for 8 weeks and then re-evaluated. Non-responders (patients with oesophageal symptoms ≥3 times per week) underwent 24 hour multichannel intraluminal impedance-pH monitoring.. Of 573 consecutive patients, 92 with oesophageal symptoms and classified as PPI-refractory underwent the esomeprazole trial; 60 did not respond. IBS, epigastric pain, and post-prandial distress episodes were associated with a poor response on multivariate analysis. NERD, reflux hypersensitivity, and functional heartburn patients constituted 32%, 42%, and 26%, respectively of the PPI-refractory group.. True refractoriness in patients with GERD symptoms attending a secondary care setting is lower than previously reported. Following a careful history and optimal PPI dosing, the rate of refractoriness was 20%. True NERD constitutes only a third of the PPI-refractory group.

Topics: Adult; Aged; Deglutition Disorders; Drug Resistance; Eructation; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Heartburn; Humans; Irritable Bowel Syndrome; Middle Aged; Prevalence; Prospective Studies; Proton Pump Inhibitors

Approximately 60% of patients presenting to dentists with erosive tooth wear have significant gastroesophageal reflux (GERD), despite minor reflux symptoms. No longitudinal studies of reflux-associated erosive tooth wear and of reflux characteristics have been reported to date. The aim of this study was to characterize the longitudinal course of GERD and of associated erosive tooth wear, as well as factors predictive of its progression, in a large group of patients.. Seventy-two patients presenting to dentists with clinically significant erosive tooth wear and increased esophageal acid exposure by 24-h multichannel intraluminal pH-impedance measurement (MII-pH) were re-assessed clinically and by MII-pH after 1 year treatment with esomeprazole 20 mg twice-daily. Predictive factors for erosive tooth wear were assessed by logistic regression.. At follow-up, no further progression in erosive tooth wear was observed in 53 (74%) of patients. The percentage of time with a pH < 4, the number of acid reflux episodes and the percentage of proximal esophageal reflux off-PPI did not change significantly after one year, but the number of weakly acidic reflux episodes decreased significantly in the large subgroup without progression. None of the baseline demographic, clinical, endoscopic or esophageal acid exposure characteristics were significantly associated with progression of erosive tooth wear at follow-up.. In this longitudinal study in patients with erosive tooth wear and oligosymptomatic GERD receiving esomeprazole for one year, erosive tooth wear did not progress further in the majority of patients. Background acidic esophageal reflux exposure appeared stable over time, whereas weakly acidic exposure decreased significantly in patients without erosion progression. MII-pH measurements on-PPI and with healthy controls will be useful in the further elucidation of the causal role of reflux in erosive tooth wear.. ClinicalTrials.gov , retrospectively registered: NCT02087345 .

Topics: Adult; Disease Progression; Esomeprazole; Esophageal pH Monitoring; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Longitudinal Studies; Male; Proton Pump Inhibitors; Tooth Erosion

Proton pump inhibitors are among the most commonly used drugs worldwide. They are considered to be largely safe and cause little side-effects. We report a 69-year-old woman who suffered from erythematous plaques 2 months after initiating therapy with esomeprazole. The diagnosis of subacute cutaneous lupus erythematosus was based on the clinical picture together with characteristic histological features of a skin biopsy specimen and the detection of anti-Ro/SSA antibodies. In particular, the temporal relationship with the onset of proton pump inhibitor therapy led to the high-level suspicion of a drug-induced pathogenesis. Strengthening the initially suspected diagnosis, the characteristic skin lesions resolved almost completely without specific therapy after discontinuation of the medication. If typical skin lesions occur in light-exposed areas in connection with the administration of PPI, the possibility of a drug-induced cutaneous lupus erythematosus should always be considered. Due to the frequent recurrence rate after renewed exposure, a new therapy with PPI should be avoided.. Protonenpumpeninhibitoren gehören zu den weltweit am häufigsten verwendeten Arzneimitteln. Sie gelten als weitgehend sicher und nebenwirkungsarm. Wir berichten über eine 69-jährige Patientin, bei der 2 Monate nach Einleitung einer Therapie mit Esomeprazol anuläre erythematöse Plaques überwiegend an lichtexponierten Körperstellen auftraten. Anhand des klinischen Bildes, dem histologischen Befund eines Hautbioptats und dem Nachweis von Anti-Ro/SSA-Antikörpern wurde die Diagnose eines subakut kutanen Lupus erythematodes gestellt. Insbesondere der zeitliche Zusammenhang mit dem Beginn der Protonenpumpeninhibitor-Therapie begründete den hochgradigen Verdacht auf eine medikamenteninduzierte Genese. Nach Absetzen von Esomeprazol waren die charakteristischen Hautveränderungen ohne spezifische Therapie nahezu vollständig rückläufig, was die anfängliche Verdachtsdiagnose erhärtete. Beim Auftreten typischer Hautveränderungen in lichtexponierten Arealen im zeitlichen Zusammenhang mit der Einnahme von PPI sollte daher immer auch an die Möglichkeit eines medikamenteninduzierten kutanen Lupus erythematodes gedacht werden. Aufgrund der häufigen Rezidive nach erneuter Exposition sollte eine erneute Therapie mit PPI vermieden werden.

Topics: Aged; Biopsy; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Lupus Erythematosus, Cutaneous; Proton Pump Inhibitors

Food and Drug Administration approval of proton-pump inhibitors for infantile gastroesophageal reflux disease has been limited by intrapatient variability in the clinical assessment of gastroesophageal reflux disease. For children 1 to 17 years old, extrapolating efficacy from adults for IV esomeprazole was accepted. The oral formulation was previously approved in children. Exposure-response and exposure matching analyses were sought to identify approvable pediatric doses.. Intragastric pH biomarker comparisons between children and adults were conducted. Pediatric doses were selected to match exposures in adults and were based on population pharmacokinetic (PK) modeling and simulations with pediatric esomeprazole data. Observed IV or oral esomeprazole PK data were available from 50 and 117 children, between birth and 17 years, respectively, and from 65 adults, between 20 and 48 years. A population PK model developed using these data was used to simulate steady-state esomeprazole exposures for children at different doses to match the observed exposures in adults.. Exposure-response relationships of intragastric pH measures were similar between children and adults. The PK simulations identified a dosing regimen for children that results in comparable steady-state area under the curve to that observed after 20 mg in adults. For IV esomeprazole, increasing the infusion duration to 10 to 30 minutes in children achieves matching Cmax values with adults.. The exposure-matching analysis permitted approval of an esomeprazole regimen not studied directly in clinical trials. Exposure-response for intragastric pH-permitted approval for the treatment of gastroesophageal reflux disease in children in whom it was not possible to evaluate the adult primary endpoint, mucosal healing assessed by endoscopy.

Topics: Administration, Oral; Adolescent; Adult; Area Under Curve; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Approval; Drug Dosage Calculations; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Male; Middle Aged; Proton Pump Inhibitors; Treatment Outcome; United States; United States Food and Drug Administration; Young Adult

Topics: Esomeprazole; Esophagitis; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Intra-Abdominal Fat; Proton Pump Inhibitors

The prevalence of gastroesophageal reflux disease (GERD) symptoms has not been investigated in patients on maintenance hemodialysis in Japan, and few studies have reported the effect of proton pump inhibitors (PPIs) in hemodialysis patients with GERD symptoms. Here, we investigated the prevalence of GERD symptoms and the effects of the PPI esomeprazole on the quality of life related to reflux and dyspepsia in patients on maintenance hemodialysis.. This was a cross-sectional/cohort study of hemodialysis outpatients implemented in 10 Japanese medical facilities from October 2012 to March 2014. The trial was registered in the UMIN Clinical Trial Registry (UMIN000009124).. Forty-one of 385 patients (11%) reported GERD symptoms on the Global Overall Symptom (GOS) questionnaire. Multivariate logistic regression analysis identified the independent prognostic factors for GERD symptoms as a history of gastric ulcer and use of sevelamer hydrochloride or calcium polystyrene sulfonate. Participants with GERD symptoms completed the Quality of Life in Reflux and Dyspepsia, Japanese version (QOLRAD-J) questionnaire and were assigned to receive 4-week esomeprazole treatment (20 mg/day). This PPI therapy significantly improved all QOLRAD-J domains in the full analysis set (n = 28) and improved the GERD symptoms listed in the GOS questionnaire. Significantly impaired disease-specific quality of life (QOL) in the QOLRAD-J domains was observed in 44.4-74.1% of patients who had symptoms before treatment. The mean GOS and QOLRAD-J scores correlated significantly.. Therapy with 20 mg/day esomeprazole appears to be efficacious for improving disease-specific QOL and GERD symptoms in Japanese patients on maintenance hemodialysis.

Topics: Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Dyspepsia; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Japan; Kidney Diseases; Logistic Models; Male; Middle Aged; Multivariate Analysis; Prevalence; Proton Pump Inhibitors; Quality of Life; Remission Induction; Renal Dialysis; Surveys and Questionnaires; Time Factors; Treatment Outcome

Topics: Administration, Oral; Adult; Drug Eruptions; Esomeprazole; Female; Gastroesophageal Reflux; Hand Dermatoses; Humans; Lansoprazole; Male; Proton Pump Inhibitors; Stomach Ulcer

Topics: Anti-Ulcer Agents; Anticoagulants; Drug Interactions; Drug Resistance; Esomeprazole; Esophagitis; Gastroesophageal Reflux; Humans; International Normalized Ratio; Male; Middle Aged; Phenindione; Venous Thrombosis

Topics: Drug Costs; Esomeprazole; Gastroesophageal Reflux; Humans; Medicare Part D; United States

Up to half of gastroesophageal reflux disease (GERD) patients report having heartburn that awakens them from sleep during the night. Recumbent-awake and conscious awakenings from sleep during the night are commonly associated with acid reflux events. The aim of the study was to assess the effect of esomeprazole 40 mg once daily on nighttime acid reflux, frequency of conscious awakenings associated with acid reflux and the recumbent-awake period.. Patients with heartburn and/or regurgitation at least three times a week were eligible for this study. All patients underwent upper endoscopy and were evaluated by demographic, Epworth Sleepiness scale, Berlin and GERD symptom checklist questionnaires. Subjects then underwent esophageal pH testing concomitantly with an actigraphy. All subjects were given esomeprazole 40 mg once daily for 7 days and completed a daily symptom record diary. On day 7, subjects repeated the pH test with actigraphy.. Twenty patients (mean age of 48.95 ± 18.69, age range 20-81 years) were enrolled. Esophageal acid exposure parameters, during recumbent-awake, recumbent-asleep, and conscious awakenings were significantly improved on last day of treatment as compared to baseline (p < 0.05). However, the frequency and duration of conscious awakenings and duration of recumbent-awake period did not improve as compared to baseline (p > 0.05).. While esomeprazole significantly reduced esophageal acid exposure during conscious awakenings and recumbent-awake and asleep periods, it did not decrease the number and duration of conscious awakening or duration of recumbent-awake period.

Topics: Adult; Aged; Aged, 80 and over; Esomeprazole; Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Proton Pump Inhibitors; Sleep Initiation and Maintenance Disorders; Young Adult

Topics: Adult; Biopsy; Choristoma; Duodenal Diseases; Duodenoscopy; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Intestinal Polyps; Proton Pump Inhibitors; Stomach

Control of chronic gastro-oesophageal reflux disease may be achieved either by anti-reflux surgery (ARS) or by long-term medical therapy with proton pump inhibitors (PPIs). The primary efficacy results of the SOPRAN study, comparing long-term omeprazole use with open ARS, and the LOTUS study, comparing long-term esomeprazole use with laparoscopic ARS, have been reported. A secondary objective of these studies was to address the long-term safety of these respective therapeutic strategies and thereby provide a valid scientific platform for assessing long-term PPI safety.. To assess the safety of long-term PPI therapy with omeprazole and esomeprazole through analyses of data from the randomised SOPRAN and LOTUS studies.. Safety data were collected from patients during the 12-year period of the SOPRAN study (n = 298) and the 5-year period of the LOTUS study (n = 514). Reported serious adverse events (SAEs) and changes in laboratory variables were analysed.. Across both studies, SAEs were reported at a similar frequency in the PPI and ARS treatment groups. Taking the time frames into consideration, the number of fatal SAEs in the two studies was low in both treatment groups. Laboratory results, including routine haematology and tests for liver enzymes, electrolytes, vitamin D, vitamin B12 , folate and homocysteine, showed no clinically relevant changes over time. As expected, gastrin and chromogranin A were elevated in the PPI groups, with the greatest increases observed in the first year.. No major safety concerns arose during 5-12 years of continuous PPI therapy. (ClinicalTrials.gov: NCT00251927 and NCT00256737).

Topics: Aged; Chromogranin A; Esomeprazole; Female; Gastrins; Gastroesophageal Reflux; Humans; Laparoscopy; Male; Middle Aged; Omeprazole; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Young Adult

Topics: Child; Child, Preschool; Esomeprazole; Gastroesophageal Reflux; Humans; Infant; Proton Pump Inhibitors

Topics: Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Omeprazole; Proton Pump Inhibitors

Topics: Esomeprazole; Gastroesophageal Reflux; Heartburn; Humans; Proton Pump Inhibitors; Severity of Illness Index

Topics: Child; Esomeprazole; Gastroesophageal Reflux; Humans; Infant; Pediatrics; Proton Pump Inhibitors

Both omeprazole and its S enantiomer (esomeprazole) have been available and used to treat symptoms of gastroesophageal reflux disease (GERD) and conditions associated with excessive stomach acid secretion for more than a decade. Controversy exists over improved efficacy of S enantiomer (esomeprazole) over parent racemate (omeprazole). However, a comparison of the clinical outcomes of these products may reveal the rationale for switching from the racemate to single enantiomer. Since enantiomers of omeprazole are equipotent, we compared the outcomes of equal doses of each product to see if both actually differ in their efficacy's or the reported superiority of S enantiomer is just a dose effect.. A web search was carried out for randomized controlled trials with head-to-head comparisons of omeprazole and S-omeprazole. The data were abstracted and after calculating the odd ratios (OR) for the outcomes reported in each study, the combined overall odd ratios (OR') were estimated. The random effect inverse variance method with omeprazole as the reference (OR" = 1) was used.. Out of 1171 studies, 14 were deemed eligible. There was no significant difference in the therapeutic success between omeprazole and S-omeprazole as a part of triple therapy for the treatment of H. pylori in both intention-to-treat (OR', 1.06; CI, 0.83, 1.36; p = 0.63) as well as per-protocol analysis (OR', 1.07; CI, 0.84, 1.36; p = 0.57). For the treatment of gastro-oesophageal reflux disease, S-omeprazole was significantly but marginally superior to the racemate (OR', 1.18; CI, 1.01, 1.38; p = 0.04). The two products were equipotent in all metrics used to assess intragastric pH except for the % patients maintaining a 24 h gastric pH above 4 (1.57; CI, 1.04, 2.381; p = 0.03).. The therapeutic benefit of chiral switch of omeprazole is questionable considering the substantially greater economic burden involved.

Topics: Esomeprazole; Gastroesophageal Reflux; Helicobacter Infections; Humans; Omeprazole; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Stereoisomerism

Limited data exist on the impact of regurgitation on health-related quality of life (HRQOL) in gastro-oesophageal reflux disease (GORD). We assessed the relationship between regurgitation frequency and HRQOL before and after acid suppression therapy in GORD.. We used data from two randomised trials of AZD0865 25-75 mg/day versus esomeprazole 20 or 40 mg/day in non-erosive reflux disease (NERD) (n=1415) or reflux oesophagitis (RO) (n=1460). The Reflux Disease Questionnaire was used to select patients with frequent and intense heartburn for inclusion and to assess treatment response. The Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire was used to assess HRQOL.. At baseline, 93% of patients in both the NERD and RO groups experienced regurgitation. Mean QOLRAD scores were similar for NERD and RO at baseline and at week 4 and disclosed decremental HRQOL with increasing frequency of regurgitation; a clinically relevant difference of >0.5 in mean QOLRAD scores was seen with regurgitation ≥4 days/week versus <4 days/week. The prevalence of frequent, persistent regurgitation (≥4 days/week) at week 4 among heartburn responders (≤1 day/week of mild heartburn) was 28% in NERD and 23% in RO. QOLRAD scores were higher among heartburn responders. There was a similar pattern of impact related to regurgitation frequency in heartburn responders compared with the group as a whole.. Frequent regurgitation was associated with a clinically relevant, incremental decline in HRQOL beyond that associated with heartburn before and after potent acid suppression in both NERD and RO.. NCT00206284 and NCT00206245.

Topics: Antacids; Drug Administration Schedule; Esomeprazole; Esophagitis, Peptic; Follow-Up Studies; Gastroesophageal Reflux; Heartburn; Humans; Imidazoles; Proton Pump Inhibitors; Pyridines; Quality of Life; Randomized Controlled Trials as Topic; Retrospective Studies; Surveys and Questionnaires; Treatment Outcome

Topics: Adult; Antidepressive Agents, Second-Generation; Citalopram; Esomeprazole; Female; Gastritis; Gastroesophageal Reflux; Humans; Irritable Mood; Mood Disorders; Proton Pump Inhibitors

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Pantoprazole; Proton Pump Inhibitors

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Pantoprazole; Proton Pump Inhibitors

Recently, it has been suggested that low esophageal basal impedance may reflect impaired mucosal integrity and increased acid sensitivity. We aimed to compare baseline impedance levels in patients with heartburn and pathophysiological characteristics related to functional heartburn (FH) divided into two groups on the basis of symptom relief after proton pump inhibitors (PPIs).. Patients with heartburn and negative endoscopy were treated with esomeprazole or pantoprazole 40 mg daily for 8 weeks. According to MII-pH (off therapy) analysis, patients with normal acid exposure time (AET), normal reflux number, and lack of association between symptoms and refluxes were selected; of whom 30 patients with a symptom relief higher than 50% after PPIs composed Group A, and 30 patients, matched for sex and age, without symptom relief composed Group B. A group of 20 healthy volunteers (HVs) was enrolled. For each patient and HV, we evaluated the baseline impedance levels at channel 3, during the overnight rest, at three different times.. Group A (vs Group B) showed an increase in the following parameters: mean AET (1.4 ± 0.8% vs 0.5 ± 0.6%), mean reflux number (30.4 ± 8.7 vs 24 ± 6.9), proximal reflux number (11.1 ± 5.2 vs 8.2 ± 3.6), acid reflux number (17.9 ± 6.1 vs 10.7 ± 6.9). Baseline impedance levels were lower in Group A than in Group B and in HVs (p < 0.001).. Evaluating baseline impedance levels in patients with heartburn and normal AET could achieve a better understanding of pathophysiology in reflux disease patients, and could improve the distinction between FH and hypersensitive esophagus.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Electric Impedance; Esomeprazole; Esophageal pH Monitoring; Esophagus; Female; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Pantoprazole; Proton Pump Inhibitors

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Autoantibodies; Biopsy; Diagnosis, Differential; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Lupus Erythematosus, Cutaneous; Male; Middle Aged; Pantoprazole; Pregnancy; Proton Pump Inhibitors; Skin

Topics: Adult; Esomeprazole; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors

Topics: Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Proton Pump Inhibitors

Topics: Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Proton Pump Inhibitors

To analyze risk factors for refractoriness to proton pump inhibitors (PPIs) in patients with non-erosive reflux disease (NERD).. A total of 256 NERD patients treated with the PPI esomeprazole were enrolled. They were classified into symptom-free and residual symptoms groups according to Quality of Life in Reflux and Dyspepsia (QolRad) scale. All subjects completed questionnaires on psychological status (self-rating anxiety scale; self-rating depression scale) and quality of life scale (Short Form 36). Multivariate analysis was used to determine the predictive factors for PPI responses.. According to QolRad, 97 patients were confirmed to have residual reflux symptoms, and the remaining 159 patients were considered symptom free. There were no significant differences between the two groups in lifestyle factors (smoking and alcohol consumption), age, Helicobacter pylori infection, and hiatal hernia. There were significant differences between the two groups in relation to sex, psychological distress including anxiety and depression, body mass index (BMI), and irritable bowel syndrome (IBS) (P < 0.05). Logistic regression analysis found that BMI < 23, comorbid IBS, anxiety, and depression were major risk factors for PPI resistance. Symptomatic patients had a lower quality of life compared with symptom-free patients.. Some NERD patients are refractory to PPIs and have lower quality of life. Residual symptoms are associated with psychological distress, intestinal disorders, and low BMI.

Topics: Aged; Anxiety; Asian People; Body Mass Index; China; Comorbidity; Depression; Drug Resistance; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Irritable Bowel Syndrome; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Proton Pump Inhibitors; Quality of Life; Risk Factors; Sex Factors; Surveys and Questionnaires

Dexlansoprazole is a new proton pump inhibitor (PPI) with a dual delayed-release system. Both dexlansoprazole and esomeprazole are an enantiomer of lansoprazole and omeprazole respectively. However, there is no head-to-head trial data or indirect comparison analyses between dexlansoprazole and esomeprazole.. To compare the efficacy of dexlansoprazole with esomeprazole in healing erosive oesophagitis (EO), the maintenance of healed EO and the treatment of non-erosive reflux disease (NERD).. Randomised Controlled Trials (RCTs) comparing dexlansoprazole or esomeprazole with either placebo or another PPI were systematically reviewed. Random-effect meta-analyses and adjusted indirect comparisons were conducted to compare the treatment effect of dexlansoprazole and esomeprazole using a common comparator. The relative risk (RR) and 95% confidence interval (CI) were calculated.. The indirect comparisons revealed significant differences in symptom control of heartburn in patients with NERD at 4 weeks. Dexlansoprazole 30 mg was more effective than esomeprazole 20 mg or 40 mg (RR: 2.01, 95% CI: 1.15-3.51; RR: 2.17, 95% CI: 1.39-3.38). However, there were no statistically significant differences between the two drugs in EO healing and maintenance of healed EO. Comparison of symptom control in healed EO was not able to be made due to different definitions used in the RCTs.. Adjusted indirect comparisons based on currently available RCT data suggested significantly better treatment effect in symptom control of heartburn in patients with NERD for dexlansoprazole against esomeprazole. No statistically significant differences were found in other EO outcomes. However, these study findings need to be interpreted with caution due to small number of studies and other limitations.

Topics: Dexlansoprazole; Dose-Response Relationship, Drug; Esomeprazole; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome

Proton pump inhibitors (PPIs) are gastric acid-suppressing agents widely prescribed for the treatment of gastroesophageal reflux disease. Recently, several studies in patients with acute coronary syndrome have raised the concern that use of PPIs in these patients may increase their risk of major adverse cardiovascular events. The mechanism of this possible adverse effect is not known. Whether the general population might also be at risk has not been addressed.. Plasma asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. Elevated plasma ADMA is associated with increased risk for cardiovascular disease, likely because of its attenuation of the vasoprotective effects of endothelial nitric oxide synthase. We find that PPIs elevate plasma ADMA levels and reduce nitric oxide levels and endothelium-dependent vasodilation in a murine model and ex vivo human tissues. PPIs increase ADMA because they bind to and inhibit dimethylarginine dimethylaminohydrolase, the enzyme that degrades ADMA.. We present a plausible biological mechanism to explain the association of PPIs with increased major adverse cardiovascular events in patients with unstable coronary syndromes. Of concern, this adverse mechanism is also likely to extend to the general population using PPIs. This finding compels additional clinical investigations and pharmacovigilance directed toward understanding the cardiovascular risk associated with the use of the PPIs in the general population.

Topics: Amidohydrolases; Animals; Arginine; Biomarkers; Cardiovascular Diseases; Cells, Cultured; Disease Models, Animal; Endothelium, Vascular; Esomeprazole; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type III; Proton Pump Inhibitors; Risk Factors; Vasodilation

To assess the drug utilization patterns for proton pump inhibitors (PPIs) prescriptions dispensed in periods with and without restrictions on reimbursement in a public healthcare system.. Data on all PPI prescriptions dispensed for gastroesophageal reflux disease (GERD) was retrieved from the Norwegian Prescription Database (NorPD) from 1 January 2004 to 31 January 2008. PPI utilization patterns were studied in new and current users of PPI in periods affected and not affected by a change in prescription policy.. The policy change resulted in 39% of esomeprazole patients discontinuing PPI therapy during a 12-month period while 23% discontinued PPI therapy during a period not affected by the policy change. The shift frequency to a different PPI was low, 5% and 7% respectively, during periods not affected by policy change. Despite a required shift in most esomeprazole patients, 64% still continued on esomeprazole. Among the 36% who shifted from esomeprazole to a different PPI, 25% subsequently shifted back to esomeprazole. In new PPI users, the proportion of esomeprazole users declined from 57% before to 20% after the introduction of the policy change.. Despite GERD being a chronic disease in most patients, there was a high degree of alteration seen in the utilization patterns of PPIs. A high proportion discontinued PPI therapy indicating mild symptoms or remission. The switching between different PPIs was low indicating good efficacy and tolerability in most patients. The policy change was more effective in new PPI users compared with the mandated shift in ongoing esomeprazole users.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Drug Substitution; Esomeprazole; Gastroesophageal Reflux; Health Policy; Humans; Insurance, Health, Reimbursement; Lansoprazole; Norway; Omeprazole; Pantoprazole; Proton Pump Inhibitors

Up to 40% of patients with gastroesophageal reflux disease fail to respond to proton pump inhibitor therapy.. To determine predictors of clinical response of proton pump inhibitor therapy.. Consecutive patients with gastroesophageal reflux disease were enrolled prospectively. All patients underwent upper endoscopy and 24-h multichannel intraluminal impedance and pH monitoring before receiving esomeprazole 20 mg b.i.d. for 2 months. Multivariate logistic regression analysis was used to determine the independent predictors of clinical response to proton pump inhibitor therapy.. A total of 204 patients with typical reflux symptoms were recruited and screened. Among them 153 patients (mean age 46.3 ± 10.6 years, 51.0% female) completed all the examinations and were assigned to proton pump inhibitor therapy. Ninety-five patients (62.1%) responded to acid suppression after 2 months. Multivariate logistic analysis showed that the predictor for response was pathological distal esophageal acid reflux (P = 0.001). The factors associated with proton pump inhibitor therapy failure were the presence of irritable bowel syndrome alone (P = 0.006), depression (P = 0.005), and overlap of irritable bowel syndrome and functional dyspepsia (P = 0.002).. The clinical response of acid suppression on gastroesophageal reflux disease could be predicted by clinical and pH parameters rather than impedance data.

Topics: Adult; Asian People; China; Depression; Dyspepsia; Esomeprazole; Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Humans; Irritable Bowel Syndrome; Male; Middle Aged; Multivariate Analysis; Proton Pump Inhibitors; Treatment Failure

The evolution of gastro-oesophageal reflux disease (GERD) under current management options remains uncertain.. To examine whether, depending on the initial presentation, non-erosive (NERD) and erosive reflux disease (ERD) without Barrett's oesophagus will progress to more severe disease under current routine care following the resolution of the initial condition.. Patients with the primary symptom of heartburn were included at baseline, and stratified into non-erosive (NERD) and erosive reflux disease (ERD), LA grades A-D (Los Angeles classification). After a 2- to 8-week course with esomeprazole therapy to achieve endoscopic healing in ERD and symptom relief in NERD, patients were treated routinely at the discretion of their physician. We report oesophagitis status and the presence of endoscopic and confirmed Barrett's oesophagus after 5 years.. A total of 6215 patients were enrolled in the study of whom 2721 patients completed the 5-year follow-up. Progression, regression and stability of GERD severity were followed from baseline to 5 years. Only a few patients with NERD and mild/moderate ERD progressed to severe forms of ERD and even Barrett's oesophagus. Most patients remained stable or showed improvement in their oesophagitis; 5.9% of the NERD patients, 12.1% of LA grade A/B patients and 19.7% of LA grade C/D patients in whom no Barrett's oesophagus was recorded at baseline progressed to endoscopic or confirmed Barrett's oesophagus at 5 years.. Most GERD patients remain stable or improve over a 5-year observation period under current routine clinical care.

Topics: Adult; Aged; Antacids; Anti-Ulcer Agents; Cohort Studies; Disease Progression; Endoscopy, Gastrointestinal; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Time Factors

Although most patients with gastroesophageal reflux disease (GERD) achieve substantial symptom relief with acid suppression, many have some residual symptoms. We evaluated the responsiveness of regurgitation, characterized by the reflux disease questionnaire (RDQ) to potent acid suppression.. We analyzed data from 2 randomized controlled trials of AZD0865 (a potassium-competitive acid blocker) 25-75 mg/day vs esomeprazole 20-40 mg/day for the treatment of nonerosive reflux disease (NERD, n = 1460) or reflux esophagitis (RE, n = 1514). Inclusion criteria for both studies were high-severity substernal burning (≥4 days per week of at least moderate intensity) during the week before enrollment. Pooled data from all treatment arms were used to ascertain the response of the reflux disease questionnaire regurgitation items to potent acid suppression during the fourth week of treatment.. When the study began, 93% of patients with NERD or RE had either "acid taste in the mouth" (regurgitation-taste) or "unpleasant movement of material upwards from the stomach" (regurgitation-movement). Either or both symptoms were present and severe in 53% of NERD (n = 717) and 54% of RE patients (n = 751) for the main study outcome. During week 4 of therapy, patients with severe "regurgitation-taste" and "regurgitation-movement" responded significantly less well than patients with NERD and high severity "substernal burning" (34% and 26% vs 49%) or those with RE (44% and 33% vs 55%). There were no differences in symptom response between patients with healed and nonhealed RE.. Regurgitation was less responsive to acid suppression than heartburn in patients with gastroesophageal reflux disease, indicating that persistent regurgitation is a common cause of incomplete treatment response.

Topics: Anti-Ulcer Agents; Esomeprazole; Gastroesophageal Reflux; Heartburn; Humans; Imidazoles; Laryngopharyngeal Reflux; Pyridines; Randomized Controlled Trials as Topic; Treatment Outcome

The Reflux Disease Questionnaire (RDQ) contains six symptom items for diagnosing and gauging gastroesophageal reflux disease (GERD) severity. However, clinical trials have generally focused only on the "substernal burning" item and limited data exist on the effect of concomitant items on the treatment response of "substernal burning".. Data from two large randomized trials of AZD0865 25-75 mg/day vs. esomeprazole 20 or 40 mg/day in patients with GERD defined by moderate to severe (≥ 4 days per week) "substernal burning" (non-erosive reflux disease (NERD), N = 1,460; reflux esophagitis (RE), N = 1,514) were re-analyzed. As no differences were found between drugs or doses in treatment response of "substernal burning", pooled data were used to determine the impact of additional RDQ items on the response of "substernal burning" to acid suppression.. At baseline, patients reported an average of four RDQ items. "Substernal burning" was the most responsive to therapy in the 3.3% of individuals with this as their only baseline RDQ symptom. The report of any other RDQ item was associated with a reduction in the responsiveness of "substernal burning" to acid suppression (e.g., RE patients with high severity "dyspepsia-pain" had an odds ratio of 0.20 for an improvement in "substernal burning" to treatment).. Other concomitant RDQ items, particularly "substernal pain" or "dyspepsia-pain", were associated with a reduced treatment effect of acid suppression on "substernal burning". These findings support the use of a more comprehensive assessment of disease state and treatment response in GERD trials and clinical practice.

Topics: Adult; Anti-Ulcer Agents; Esomeprazole; Esophagitis, Peptic; Gastroesophageal Reflux; Heartburn; Humans; Retrospective Studies; Surveys and Questionnaires; Treatment Outcome

The efficacy of proton-pump inhibitor (PPI) therapy often is assessed to determine whether patients' symptoms are acid-related and if patients have gastroesophageal reflux disease (GERD), although the accuracy of this approach is questionable. We evaluated the diagnostic performance of the PPI test, in conjunction with other tests, for the diagnosis of GERD.. We analyzed data from the DIAMOND study, a multinational trial that compared the ability of the reflux disease questionnaire with that of symptom-based clinical diagnosis to identify GERD in primary care patients with frequent upper-gastrointestinal symptoms. Patients (n = 308) were given placebo and further evaluated by endoscopy, wireless esophageal pH-metry, and symptom association monitoring. Those with GERD (n = 197) were identified based on the presence of reflux esophagitis, esophageal pH level less than 4 for more than 5.5% of 24 hours, or positive results from symptom association monitoring (or a positive result from the PPI test in patients with borderline levels of esophageal acidity). All patients then were given single-blind therapy with esomeprazole (40 mg once daily) for 2 weeks and symptoms were recorded daily.. A positive response to the PPI test was observed in 69% of patients with GERD and in 51% of those without GERD. Response to placebo did not influence the diagnostic ability of the subsequent PPI test. More patients with reflux esophagitis had a positive result from the PPI test than patients without GERD (57% vs 35%; P = .002) or patients with GERD but no esophagitis. A clinical diagnosis by the primary care physician of an acid-related disease was not associated with response to PPIs.. In a well-characterized population of primary care patients with frequent upper-gastrointestinal symptoms of any type, the PPI test has limited ability to identify patients with GERD, diagnosed by current standard tests. (ClinicalTrials.gov Number, NCT00291746.).

Topics: Clinical Medicine; Esomeprazole; Esophageal pH Monitoring; Esophagoscopy; Gastroesophageal Reflux; Humans; Placebos; Primary Health Care; Proton Pump Inhibitors; Sensitivity and Specificity; Single-Blind Method; Surveys and Questionnaires

Although most patients with gastro-oesophageal reflux disease (GERD) benefit from proton pump inhibitor (PPI) therapy, some experience only partial symptom relief.. To determine the prevalence of partial heartburn response to PPIs and its impact on health-related quality of life.. Four randomised, double-blind studies in adults with reflux disease compared esomeprazole 40 mg/day or 20 mg/day with omeprazole 20 mg/day, or esomeprazole 40 mg/day with pantoprazole 40 mg/day. Patients with heartburn on ≥4 days during the 1-week recall period at baseline were included. Partial response was defined as heartburn on ≥3 days during the last treatment week and reduced heartburn frequency after 4 weeks of treatment compared with baseline.. The analysis included 2645 patients with non-erosive reflux disease (mean age: 48.8 years; 54.4% women) and 3151 patients with reflux oesophagitis (mean age: 50.6 years; 37.1% women). At baseline, most patients reported heartburn on 5-7 days (non-erosive reflux disease: 82.2%; reflux oesophagitis: 86.8%). Partial heartburn response occurred in 19.9% of patients with non-erosive reflux disease and 14.0% with reflux oesophagitis. Defining partial response as heartburn on ≥2 days increased these rates to 26.2% and 19.3%, respectively; defining partial response as heartburn of moderate or severe intensity on ≥3 days decreased these rates to 6.4% and 5.3%, respectively. Nonresponse to PPIs was rare (non-erosive reflux disease: 2.4%; reflux oesophagitis: 1.4%).. Using our conservative definition, partial heartburn response to proton pump inhibitor therapy occurred in 14-20% of gastro-oesophageal reflux disease patients, more commonly in non-erosive reflux disease than in reflux oesophagitis.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index; Time Factors; Treatment Outcome

Topics: Esomeprazole; Gastroesophageal Reflux; Humans; Primary Health Care; Proton Pump Inhibitors

Histological Barrett's esophagus, defined as specialized intestinal metaplasia (SIM+) at the cardia without endoscopic suspicion of columnar epithelium, is found frequently in biopsies at the gastro-esophageal junction although its clinical relevance is unknown. The authors aim was to evaluate prospectively the progression of SIM+ to macroscopically evident Barrett's esophagus (BE/SIM+), and to identify risk factors for this progression.. Data were obtained from a sub-group of patients (no visible BE at presentation, but SIM+) included in the ProGERD study, a prospective evaluation of the clinical course of GERD under routine clinical care. They had esomeprazole 20-40 mg/day for 2-8 weeks. Symptom assessment was performed annually, and endoscopy with biopsy was planned at baseline, after healing treatment and after 2 and/or 5 years.. 128 of 171 (74.8%) patients with unequivocal SIM at the z-line after healing were biopsied again after 2 and/or 5 years. At follow-up, 33 (25.8%) of these patients showed progression to BE/SIM+. Factors significantly associated with progression were smoking, a long history of GERD and severe esophagitis at baseline. Patients who had progressed to BE/SIM+ already at 2 years showed consistent findings at 5 years.. More than 20% of GERD patients with SIM+ in this study were found to have BE/SIM+ within 2-5 years. This finding supports the hypothesis that SIM+ at the cardia could be the missing link explaining increased cancer risk in GERD patients without overt BE and merits further investigation in a prospective study.

Topics: Adult; Aged; Barrett Esophagus; Biopsy; Cardia; Confidence Intervals; Endoscopy, Gastrointestinal; Esomeprazole; Esophagitis; Esophagogastric Junction; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Male; Metaplasia; Middle Aged; Odds Ratio; Prospective Studies; Proton Pump Inhibitors; Smoking; Time Factors

The predictors for treatment failure of on-demand proton pump inhibitor (PPI) therapy in gastro-esophageal reflux disease (GERD) patients are unclear. We studied the efficacy and predictors for treatment failure of step-down on-demand PPI therapy in patients with non-erosive reflux disease (NERD) and those with low grade erosive esophagitis.. Consecutive symptomatic GERD patients who had positive esophageal pH studies and complete symptom resolution with initial treatment of esomeprazole were given step-down on-demand esomeprazole for 26 weeks. Patients with esophagitis of Los Angeles (LA) grade C or above and recent use of PPI were excluded. Treatment failure was defined as an inadequate relief of reflux symptoms using global symptom assessment. Potential predictors of treatment failure were determined using multivariate analysis.. One hundred and sixty three NERD and 102 esophagitis patients were studied. The 26-week probability of treatment failure was 36.2% (95% CI: 23.9-46.5%) in NERD group and 20.1% (95% CI: 10.9-28.3%) in esophagitis group, respectively (P = 0.021). Irritable bowel syndrome (adjusted HR: 2.1, 95% CI: 1.5-3.8, P = 0.01), in addition to daily reflux symptom (adjusted hazard ratio: 2.7, 95% CI: 1.9-4.2, P = 0.001) and concomitant dyspepsia (adjusted hazard ratio: 1.7, 95% CI: 1.1-2.8, P = 0.04), were independent predictors for treatment failure.. Compared to patients with esophagitis, NERD patients have higher failure rate of on-demand PPI therapy. Concomitant irritable bowel syndrome, in addition to daily reflux symptom and dyspepsia, is associated with the failure of on-demand PPI in these patients.

Topics: Adult; Cohort Studies; Comorbidity; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Irritable Bowel Syndrome; Longitudinal Studies; Male; Manometry; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prospective Studies; Proton Pump Inhibitors; Retrospective Studies; Treatment Failure

Gastroesophageal reflux disease (GERD), including erosive reflux disease and non-erosive reflux disease (NERD), is a chronic disease with a significant negative effect on quality of life. State-of-the-art treatment involves proton pump inhibitors (PPIs). However, relapse of symptoms occurs in the majority of the patients who require recurrent or continuous therapy. Although PPIs are well tolerated, little information is available about gastrointestinal side effects.. To evaluate the effects of long-term PPI treatment on development of bowel symptoms and/or small intestinal bacterial overgrowth (SIBO).. Patients with NERD not complaining of bowel symptoms were selected by upper endoscopy, 24-h pH-metry and a structured questionnaire concerning severity and frequency of bloating, flatulence, abdominal pain, diarrhoea and constipation. Patients were treated with esomeprazole 20 mg bid for 6 months. Prior to and after 8 weeks and 6 months of therapy, patients received the structured questionnaire and underwent evaluation of SIBO by glucose hydrogen breath test (GHBT).. Forty-two patients with NERD were selected out of 554 eligible patients. After 8 weeks of PPI treatment, patients complained of bloating, flatulence, abdominal pain and diarrhoea in 43%, 17%, 7% and 2%, respectively. After 6 months, the incidence of bowel symptoms further increased and GHBT was found positive in 11/42 (26%) patients. By a post hoc analysis, a significant (P < 0·05) percentage of patients (8/42) met Rome III criteria for irritable bowel syndrome.. Prolonged PPI treatment may produce bowel symptoms and SIBO; therefore, the strategy of step-down or on-demand PPI therapy should be encouraged in GERD.

Topics: Adult; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Intestines; Irritable Bowel Syndrome; Italy; Male; Middle Aged; Proton Pump Inhibitors; Time Factors

Erosive oesophagitis appears to be more common in white vs. nonwhite patients with gastro-oesophageal reflux disease (GERD).. To evaluate the association between race and erosive oesophagitis healing in patients with GERD treated with once-daily proton pump inhibitors (PPIs).. Data from five double-blind trials of once-daily treatment with esomeprazole 40mg vs. omeprazole 20mg or lansoprazole 30mg for erosive oesophagitis healing (evaluated at weeks 4 and 8 by endoscopy) were pooled and stratified by baseline race and Los Angeles (LA) severity grade. Multiple logistic regression models were fit with erosive oesophagitis healing (dependent variable) and race (independent variable), with adjustments for treatment, study, baseline LA grade, age, gender, BMI, Helicobacter pylori status, hiatal hernia and interactions of these factors with race.. Of 11,027 patients, 91% were white. Nonwhite (n=978) and black (n=613) patients were less likely to have severe baseline erosive oesophagitis (LA grade C or D) than white patients [adjusted OR: 0.69 (95% CI, 0.61-0.79) and 0.67 (0.57-0.78), respectively; P<0.0001]. At week 8, nonwhite and black patients had lower healing rates than white patients [OR: 0.75 (0.63-0.89) and 0.67 (0.54-0.83), respectively; P≤0.001]. Greater odds of healing were associated with less severe baseline LA grade, increasing age, hiatal hernia, esomeprazole treatment (vs. lansoprazole or omeprazole) and lansoprazole treatment (vs. omeprazole) (all P≤0.0009); no factor interacted significantly with race.. Nonwhite patients with GERD had less severe baseline erosive oesophagitis, but were less likely than white patients to have erosive oesophagitis healing after 8-week PPI therapy.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Aged, 80 and over; Esomeprazole; Esophagitis, Peptic; Faith Healing; Female; Gastroesophageal Reflux; Humans; Lansoprazole; Logistic Models; Los Angeles; Male; Middle Aged; Omeprazole; Proton Pump Inhibitors; Racial Groups; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome; Young Adult

The relationship between symptom elimination and normalization of esophageal acid level of gastroesophageal reflux disease (GERD) on proton-pump inhibitor (PPI) therapy has been questioned. This study aimed to evaluate the relationship between symptom response and gastro-esophageal acidity control in Chinese patients with GERD on esomeprazole therapy, and to assess the role of 24-hour esophageal pH-metry after therapy in GERD patients.. GERD patients with typical reflux symptoms were enrolled and received esomeprazole 40 mg once daily for 4 weeks. Patients with positive baseline 24-hour esophageal pH-metry were divided into two groups depending on an additional dual-channel 24-hour pH-metry after treatment. The pH- group achieved normalization of esophageal pH level whereas the pH+ group did not.. Of the 80 patients studied, 76 had abnormal baseline esophageal pH levels. Of these, 90% (52/58) of symptom-free patients and 67% (12/18) of symptom-persistent patients achieved esophageal pH normalization after therapy (P = 0.030). The mean post-therapy gastric nocturnal percent time of pH < 4.0 was significantly higher in pH+ group than that in pH- group (P < 0.001) after therapy. The multivariate regression analysis identified hiatus hernia (P < 0.001) and persistent reflux symptom (P = 0.004) were two independent factors predicting the low post-therapy esophageal pH level.. Symptom elimination is not always accompanied by esophageal pH normalization, and vice verse. Esophageal pH-metry is recommended for GERD patients with hiatus hernia or with persistent reflux symptoms after PPI therapy.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Endoscopy, Gastrointestinal; Esomeprazole; Esophageal pH Monitoring; Esophagus; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Prospective Studies; Young Adult

A 37-year-old female, who had a neuroendocrine pancreatic neoplasm, underwent duodeno-cephalo-pancreatectomy. In the 2 years following surgery, she had normal levels of serum chromogranin A (CgA), gastrin and other tumor markers. About 3 years after surgery, owing to the onset of reflux-like dyspeptic symptoms, the patient started treatment with the PPI esomeprazole. During PPI treatment, the patient's serum CgA level rose to more than three times the upper limit of normal, although her gastrin levels remained in the normal range. These findings were interpreted as being suggestive of neuroendocrine tumor relapse.. Thoraco-abdominal CT, In¹¹¹-octreotide total body scan, CT of sella turcica, Tc(99m)-sestamibi neck scan, mutational analysis of chromosome 11q13 (site of multiple endocrine neoplasia type 1 [MEN1] gene). Discontinuation of, and rechallenge with, esomeprazole.. Esomeprazole-induced hyperchromograninemia in the absence of elevated levels of fasting serum gastrin.. Discontinuation of acid-suppressive treatment and continuation of oncologic follow-up.

Topics: Adult; Anti-Ulcer Agents; Chromogranin A; Education, Medical, Continuing; Esomeprazole; Female; Gastrins; Gastroesophageal Reflux; Humans; Neuroendocrine Tumors

In some cases of drug therapy, the available evidence might be sufficient to extend the indications to children without further clinical studies.. We reviewed the available evidence for one of the categories of drugs most frequently used off-label in children: proton pump inhibitors (PPIs) used for the treatment of gastroesophageal reflux disease (GERD). A classification of the appropriateness of off-label use of PPIs in children with GERD was also performed.. Of the five PPIs evaluated, only omeprazole has a paediatric indication in Europe. Overall, 19 clinical trials were retrieved and evaluated on the basis of pharmacokinetics, efficacy and safety data. The off-label use of omeprazole, esomeprazole and lansoprazole in children was evaluated as appropriate given the consistent available evidence retrieved in literature.. This study demonstrates the existence of a large body of clinical evidence on the use of PPIs in children. Regulatory agencies and ethical committees should cope with this issue for ethical reasons to avoid unnecessary trial replication.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Child; Clinical Trials as Topic; Databases, Bibliographic; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Administration Schedule; Drug Utilization Review; Esomeprazole; European Union; Gastroesophageal Reflux; Government Agencies; Humans; Isomerism; Lansoprazole; Multicenter Studies as Topic; Omeprazole; Pediatrics; Proton Pump Inhibitors; United States; United States Food and Drug Administration

Proton pump inhibitor (PPI) therapy is known to suppress gastric acid secretion. Thus PPI therapy may decrease gastric volume and gastric contents available for gastro-oesophageal reflux by decreasing acid secretion.. To determine the effect of PPI therapy on the gastric volume after a standard meal.. A total of nine healthy subjects were studied using magnetic resonance imaging, before and after a standard liquid meal mixed with a paramagnetic contrast to help demarcate the gastric region. Images were acquired for a total of 90 min after the meal. Studies were conducted before and following esomeprazole twice daily for 7 days. Images were analysed to determine the gastric liquid volume.. Gastric volume, 15 min after the meal peaked to 611 +/- 37 mL on the control day and 539 +/- 30 mL following the PPI administration (P < 0.001). Average gastric volume remained significantly lower (56 +/- 9 mL, P < 0.05) on the PPI therapy from 5 to 75 min after the meal.. Proton pump inhibitor therapy causes a significant reduction in the gastric contents volume during first 75 min after the meal. In addition to increasing the gastric pH, PPI therapy may decrease the frequency of gastro-oesophageal reflux by decreasing the volume of gastric contents.

Topics: Adult; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Magnetic Resonance Imaging; Male; Observer Variation; Proton Pump Inhibitors; Stomach

Gastro-oesophageal reflux disease (GERD) can be associated with laryngo-respiratory symptoms (LRS) such as chronic cough, asthma or laryngeal symptoms.. To analyse the long-term clinical course of LRS in a large population with GERD and LRS.. ProGERD is a prospective multicentre cohort study of 6215 adult out-patients with GERD. At baseline, the prevalence of LRS was assessed. Initial standardized treatment was esomeprazole for up to 8 weeks. After 5 years of follow-up, patients were interviewed for LRS and a multivariate analysis was performed with resolved vs. persistent symptoms for chronic cough, asthma and laryngeal symptoms.. In all, 2886 patients (46.4%) were available for analysis at baseline and at 5 years. The prevalence of chronic cough and laryngeal disorders had decreased while the prevalence of asthma had increased. Resolution of LRS was independent of clinical reflux characteristics or PPI medication.. In a large population with GERD, only few patients reported persistent LRS over 5 years. Resolution of LRS was independent of the stage of GERD and PPI treatment. Accordingly, data on the direction of causality between GERD and LRS are lacking and the strength of the association between the two must remain controversial.

Topics: Adult; Aged; Aged, 80 and over; Epidemiologic Methods; Esomeprazole; Female; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Laryngeal Diseases; Male; Middle Aged; Outcome Assessment, Health Care; Prevalence; Young Adult

Topics: Asthma; Esomeprazole; Gastric Acid; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Proton Pump Inhibitors

Topics: Asthma; Esomeprazole; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Proton Pump Inhibitors; Respiratory Aspiration

Topics: Asthma; Esomeprazole; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Proton Pump Inhibitors; Respiratory Aspiration; Stomach

To determine treatment satisfaction in patients with gastro-oesophageal reflux disease (GORD) when switched to esomeprazole.. This observational, multicentre study conducted in the Netherlands included primary-care patients being treated with a proton pump inhibitor (PPI) [omeprazole, pantoprazole, rabeprazole or lansoprazole] for GORD who were switched to esomeprazole by their physician. After a median of 28 days' esomeprazole therapy, patients' satisfaction was assessed using a questionnaire. Patients self-rated whether they were 'more satisfied', felt there was 'no difference' or were 'less satisfied' with esomeprazole compared with previous PPI therapy. Symptom control, concomitant medication use and tolerability were also assessed.. Overall, 4929 patients were included in this study; of these, only 21.9% were satisfied with PPI treatment at consultation (i.e. prior to switching to esomeprazole). Following switching to esomeprazole therapy, 88.0% of patients were satisfied with therapy and only 26.9% of patients were still experiencing symptoms (vs 84.0% at consultation); 71.3% were more satisfied with esomeprazole than with their previous PPI, most frequently because they had fewer or no symptoms. Among patients who had been using concomitant therapy to control GORD symptoms, 62.0% were no longer using any such medication. Of the 1069 patients who had been satisfied with their previous PPI therapy, 39.4% were even more satisfied with esomeprazole. Esomeprazole was well tolerated; the most commonly reported adverse events were nausea/vomiting and headache, and no treatment-related serious adverse events occurred.. Among primary-care patients receiving PPI therapy for GORD, switching to esomeprazole therapy impacts positively on treatment satisfaction and symptom control.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Netherlands; Omeprazole; Patient Satisfaction; Primary Health Care; Proton Pump Inhibitors; Surveys and Questionnaires; Young Adult

Topics: Adult; Aged; Anti-Ulcer Agents; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Omeprazole

Long-term therapy with potent acid inhibitors is a common treatment for gastro-esophageal reflux disease. Administration of proton pump inhibitors (PPIs) causes profound and continuous hypochlorhydria by inhibition of the proton pump in gastric parietal cells. Long-term hypergastrinaemia increases mucosal thickness and enterochromaffin-like cell density in oxyntic mucosa.. The aim of this study was to see whether this very common clinical intervention induces significant changes in the gastric mucosal gene expression pattern.. Seven patients suffering from gastro-esophageal reflux disease were included in this study. Endoscopic biopsies were taken from the corpus mucosa before and toward the end of a 3-month treatment with the PPI esomeprazole.. Microarray analysis identified 186 differentially expressed genes. A high proportion of genes with changed gene expression levels during PPI treatment are involved in proliferation, apoptosis, and stress response.. This study identified many genes that were not previously known to be affected by inhibition of gastric acid secretion. Further characterization of the functional roles of genes whose expression is modulated by potent acid inhibition may give new insight into the biological responses to potent acid inhibition, including the mucosal response to the moderately increased gastrin levels encountered in clinical practice.

Topics: Adult; Aged; Anti-Ulcer Agents; Apoptosis; Biopsy; Cell Proliferation; Esomeprazole; Esophagoscopy; Female; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Gene Expression Profiling; Gene Expression Regulation; Humans; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Proton Pump Inhibitors

Proton pump inhibitors (PPIs) are one of the most widely used drug classes in the US and are now frontline medications for gastro-oesophageal reflux disease (GERD) and dyspepsia. In a previous work, we observed that a transmucosal, upper gastrointestinal (GI) leak exists in Barrett's oesophagus (BO) patients. PPI medications are commonly used by Barrett's patients.. To examine if the PPI, esomeprazole, affects the barrier function of the upper GI tract.. The sucrose permeability test (SPT) was used to assess the possible effect of the PPI, esomeprazole, on upper GI leak in 37 first-time-presenting GERD patients and 25 healthy controls.. Esomeprazole induced a significant transmucosal leak in the upper GI tract of patients taking the drug for the first time. The leak occurred quickly, within days of first taking the drug. The leak was also reversed within days of stopping the medication.. This is the first patient-based study showing that a PPI compromises upper GI barrier function. There are potential implications for transmucosal leak of other medications that a patient on a PPI may be taking, as well as possible leak of endogenous peptides/proteins. The clinical consequences of this phenomenon are currently unknown, but are potentially important.

Topics: Adult; Aged; Case-Control Studies; Esomeprazole; Female; Gastric Mucosa; Gastroesophageal Reflux; Humans; Male; Middle Aged; Permeability; Proton Pump Inhibitors; Sucrose; Young Adult

Oesophageal acidification induces dyspeptic symptoms in healthy individuals. This study aimed to evaluate the correlation between oesophageal acid exposure and dyspeptic symptoms in patients with nonerosive reflux disease.. A total of 68 patients with dominant symptoms of heartburn, negative upper gastrointestinal endoscopy and concomitant dyspeptic symptoms participated in the study. The severity of dyspepsia and reflux-related symptoms was evaluated, and 24-h gastro-oesophageal pH-monitoring study was performed in all patients at baseline and after 4 weeks of therapy with esomeprazole 40 mg.. Oesophageal basal acid exposure was pathological in 43 patients and normal in 25 patients, with a similar prevalence and severity of individual dyspeptic symptoms in the two groups. A significant correlation between reflux and dyspepsia scores was observed in the subgroup of patients with normal, but not in those with abnormal pHmetry (r=0.4, P=0.04 and r=0.2 P=0.07, respectively). After esomeprazole, a reduction in severity of dyspepsia (>or=50% with respect to baseline) was observed, independent of improvement of reflux-associated symptoms. Improvement in dyspepsia was, however, similar in patients with normal and abnormal basal acid exposure (14/25 vs. 33/43, respectively, P=NS).. Dyspeptic symptoms coexist in a subset of nonerosive reflux disease patients, but prevalence and severity of the symptoms seems to be independent of oesophageal acid exposure.

Topics: Anti-Ulcer Agents; Dyspepsia; Esomeprazole; Esophageal pH Monitoring; Female; Gastric Acid; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Treatment Outcome

Topics: Adolescent; Child; Child, Preschool; Dosage Forms; Drug Approval; Enzyme Inhibitors; Esomeprazole; Gastroesophageal Reflux; Humans; Infant; Proton Pump Inhibitors; United States; United States Food and Drug Administration

Proton pump inhibitors (PPIs) rank third among drug classes in the amount they cost the French health care system annually (more than a billion euros, i.e., 5.7% of community pharmaceutical expenditures, 50% prescribed for gastroesophageal reflux disease (GERD)).. Data for a representative sample of patients aged 20 years and older, who visited their GP at least once in 2005 for uncomplicated symptomatic GERD came from the Thales database (1200 representative general practitioners (GP) connected to a computerized network) a.. In 2005, 122 571 patients (mean age, 56 years, 45% male, 2.6 consultations for GERD) met the inclusion criteria. Extrapolated to the French population, this sample corresponds to 5.7 million people, i.e., 13% of the adult population who visited a GP during the year. PPIs were prescribed as first-line treatment for GERD in 84% of the consultations. Omeprazole, as a proprietary or generic drug, was prescribed most often (79%) and at a full dose (20mg), while other compounds (lansoprazole, pantoprazole, rabeprazole and esomeprazole) were prescribed at half dose in 64% of cases. The extrapolated annual cost of PPIs reimbursed for this indication was 465 million euros (Meuro) at a mean reimbursement level of 73%. Brand-name omeprazole still accounts for 11% of the total cost reimbursed. Complete replacement of brand-name omeprazole by its generic counterpart would reduce costs by 18.35Meuro (-4.3% reimbursed expenditure). The switch from generic full-dose omeprazole to a half dose of other PPIs would allow a further saving of 2.6 (with lansoprazole) to 13.2 Meuro (with pantoprazole).. A substantial saving in reimbursed pharmaceutical spending in uncomplicated GERD and full compliance with clinical practice recommendations could be achieved by the substitution of less expensive PPIs.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Costs and Cost Analysis; Esomeprazole; Family Practice; Female; France; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Pantoprazole; Proton Pumps; Rabeprazole

Episodes of respiratory distress with chest retraction and wheezing, sometimes associated with facial edema, were noted after administering the proton pump inhibitors omeprazole and esomeprazole in an infant with gastroesophageal reflux. The disturbances relieved dramatically after withdrawing the proton pump inhibitor.

Topics: Enzyme Inhibitors; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Infant; Lung Diseases; Omeprazole; Proton Pump Inhibitors; Respiratory Sounds

Patients with gastro-oesophageal reflux disease may complain of epigastric pain, bloating, early satiety, epigastric fullness, epigastric burning, nausea and vomiting.. To evaluate the symptoms in response to gastric distension and its relationship to a therapeutic course in patients with gastro-oesophageal reflux disease using the water load test, compared to healthy controls.. Thirty gastro-oesophageal reflux disease patients with grade A oesophagitis (studied before and after 4 weeks of therapy with esomeprazole, 40 mg per day) and 15 patients with reflux-related symptoms demonstrated at wireless pH monitoring (non-erosive reflux disease) were compared to 30 healthy volunteers.. Patients with grade A oesophagitis and with reflux-related symptoms ingested significantly lower water volumes than did controls, before onset of fullness, without statistically significant difference between erosive or non-erosive gastro-oesophageal reflux disease; this variable improved in patients after treatment. Nausea scores were higher basally in patients, pre- and post-therapy, and improved after therapy. Thirty-minute fullness and bloating scores improved after therapy in all gastro-oesophageal reflux disease patients compared to controls and pre-therapy. In all pre-treatment patients, a significant correlation was found only with epigastric fullness; after treatment, there was no significant relationship between the water load and the symptom scores.. In patients with reflux-related symptoms, with or without grade A oesophagitis, the water load test is frequently abnormal, suggesting an altered gastric function. This could explain the incomplete resolution of symptoms after treatment in some patients, and should lead to additional studies aimed at exploring gastric function in gastro-oesophageal reflux disease patients.

Topics: Adult; Drinking; Dyspepsia; Enzyme Inhibitors; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Treatment Outcome; Water

A sensitive method was developed for the simultaneous determination of omeprazole and its major metabolites 5-hydroxyomeprazole and omeprazole sulfone in human plasma by HPLC-electrospray mass spectrometry. Following liquid-liquid extraction HPLC separation was achieved on a ProntoSil AQ, C18 column using a gradient with 10 mM ammonium acetate in water (pH 7.25) and acetonitrile. The mass spectrometer was operated in the selected ion monitoring mode using the respective MH(+) ions, m/z 346 for omeprazole, m/z 362 for 5-hydroxy-omeprazole and omeprazol-sulfone and m/z 300 for the internal standard (2-{[(3,5-dimethylpyridine-2-yl)methyl]thio}-1H-benzimidazole-5-yl)methanol. The limit of quantification (LOQ) achieved with this method was 5 ng/ml for 5-hydroxyomeprazole and 10 ng/ml for omeprazole and omeprazole-sulfone using 0.25 ml of plasma. Intra- and inter-assay variability was below 11% over the whole concentration range from 5 to 250 ng/ml for 5-hydroxyomeprazol and from 10 to 750 ng/ml for omeprazole and omeprazole-sulfone. The method was successfully applied to the determination of pharmacokinetic parameters of esomeprazole and the two major metabolites after a single dose and under steady state conditions.

Topics: Chromatography, High Pressure Liquid; Esomeprazole; Gastroesophageal Reflux; Humans; Omeprazole; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization

Symptom diaries are potentially attractive but, because of concerns about patient compliance, they have had limited use in clinical trials. We assessed the validity and responsiveness of a symptom diary for patients with gastro-oesophageal reflux disease.. We included 215 patients with gastro-oesophageal reflux disease after starting treatment for 4 weeks with 40 mg esomeprazole once daily. Patients recorded whether they experienced night-time heartburn (yes/no), the severity of daytime heartburn on a scale from 1 (no heartburn) to 4 (severe heartburn) and their antacid use. Patients also completed a number of disease-specific and preference-based Health-related Quality of Life questionnaires at baseline and follow-up.. Consistent with a priori predictions, daytime heartburn showed moderate to strong correlations with the Quality of Life in Reflux and Dyspepsia questionnaire (0.36-0.67) and four scales of symptom severity (0.36-0.70) for baseline, follow-up and change scores, but low correlations with the Standard Gamble. Responsiveness of the daytime heartburn item was excellent with a mean change from baseline to follow-up of -1.3 (95% CI -1.4 to -1.1) and a standardized response mean of 1.33 while responsiveness of the daily antacid use item was moderate (mean change scores -1.8 tablets taken, 95% CI -2.3 to -1.3 and standardized response mean of 0.64).. The excellent psychometric properties of this simple gastro-oesophageal reflux disease diary make it an attractive measure for future trials.

Topics: Antacids; Anti-Ulcer Agents; Cross-Sectional Studies; Esomeprazole; Female; Gastroesophageal Reflux; Heartburn; Humans; Longitudinal Studies; Male; Medical Records; Middle Aged; Quality of Life; Severity of Illness Index; Treatment Outcome

Topics: Adult; Aged; Chronic Disease; Enzyme Inhibitors; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Laryngitis; Male; Middle Aged; Proton Pump Inhibitors; Quality of Life; Treatment Outcome

There is a controversy as to whether gastroesophageal reflux disease (GERD) exists as a spectrum of disease severity or as a categorial disease in three distinct groups: nonerosive (NERD) and erosive reflux disease (ERD) and Barrett's esophagus (BE). Aim of the study was to assess progression or regression of GERD over 2 yr in a large cohort of patients (N = 3,894) under routine clinical care in Germany, Austria, and Switzerland (ProGERD study).. Patients with predominant heartburn, with or without esophagitis, were recruited and classified according to endoscopic status at baseline, i.e., NERD, erosive reflux disease-Los Angeles (ERD-LA) grade A/B and ERD-LA grade C/D, and BE. After an initial treatment with esomeprazole, they were followed, regardless of their response. Medical therapy or endoscopy was initiated at the discretion of their primary care physician, in line with routine care. At 2 yr, endoscopy with biopsy was performed according to the protocol.. After 2 yr, 25% of patients who had NERD at baseline progressed to LA A/B and 0.6% to LA C/D; 1.6% of patients who had LA A/B progressed to LA C/D and 61% regressed to NERD; 42% of patients who had LA C/D regressed to LA A/B and 50% regressed to NERD (all figures exclude patients with confirmed BE at baseline). At 2 yr, 22% of patients had been off medication for at least 3 months. Patients with ERD-LA grade C/D were at greatest risk of developing BE: 5.8% compared with 1.4% for ERD-LA grade A/B and 0.5% for NERD.. GERD does not seem to be a categorial disease. Progression and regression between grades was observed in this large cohort of patients under routine clinical care.

Topics: Barrett Esophagus; Disease Progression; Esomeprazole; Esophageal Neoplasms; Esophagitis; Esophagoscopy; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Male; Middle Aged; Prospective Studies

This study determined the diagnostic and therapeutic response of the Reflux Disease Questionnaire (RDQ) using the symptom association probability (SAP) as reference. In addition, the RDQ's construct validity and its relationship to quality of life (QOL) were ascertained.. Seventy-four patients with GORD symptoms (age 51 years (22-78); male 62%) derived from primary care completed the RDQ, GSRS and QOLRAD before and after a 2 weeks' course of esomeprazole 40 mg daily. The SAP was determined by a 24-hour pH recording before PPI treatment. The diagnostic abilities of the RDQ (total and 4 dimensions scores) were assessed with the area under the curve (AUC) of a receiver operating curve. RDQ scores before and after PPI treatment were compared with Wilcoxon tests. Multiple linear regressions assessed the RDQ's construct validity (GSRS) and relationship to QOL (QOLRAD).. The AUCs were low for all RDQ dimensions (AUC <0.6). In the SAP-positive patients all RDQ dimensions improved (p < 0.0001) while the scores of the SAP negatives did not (heartburn p < 0.01; GORD and total score p < 0.05; regurgitation and dyspepsia n.s.). The RDQ was related to the total and reflux GSRS dimensions while the food and drink QOL dimension was linearly associated with the RDQ.. The RDQ is a valid and reliable questionnaire with excellent construct validity and a good relationship to QOL. The diagnostic value of the RDQ in primary care is limited, but combination with an additional PPI treatment course might improve the RDQ's ability to discriminate GORD patients according to their SAP outcome.

Topics: Administration, Oral; Adult; Aged; Dose-Response Relationship, Drug; Drug Administration Schedule; Esomeprazole; Family Practice; Female; Follow-Up Studies; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Monitoring, Physiologic; Patient Compliance; Probability; Quality of Life; Risk Factors; Sickness Impact Profile; Surveys and Questionnaires; Treatment Outcome

The correlation between treatment satisfaction and demographic characteristics, symptoms, or health-related quality of life (HRQL) in patients with gastroesophageal reflux disease (GERD) is unknown. The objective of this study was to assess correlates of treatment satisfaction in patients with GERD receiving a proton pump inhibitor, esomeprazole.. Adult GERD patients (n = 217) completed demography, symptom, HRQL, and treatment satisfaction questionnaires at baseline and/or after treatment with esomeprazole 40 mg once daily for 4 weeks. We used multiple linear regressions with treatment satisfaction as the dependent variable and demographic characteristics, baseline symptoms, baseline HRQL, and change scores in HRQL as independent variables.. Among the demographic variables only Caucasian ethnicity was positively associated with treatment satisfaction. Greater vitality assessed by the Quality of Life in Reflux and Dyspepsia (QOLRAD) and worse heartburn assessed by a four-symptom scale at baseline, were associated with greater treatment satisfaction. The greater the improvement on the QOLRAD vitality (change score), the more likely the patient is to be satisfied with the treatment.. Ethnicity, baseline vitality, baseline heartburn severity, and change in QOLRAD vitality correlate with treatment satisfaction in patients with GERD.

Topics: Adult; Aged; Aged, 80 and over; Canada; Demography; Enzyme Inhibitors; Esomeprazole; Female; Gastroesophageal Reflux; Heartburn; Humans; Linear Models; Male; Middle Aged; Patient Satisfaction; Quality of Life; Surveys and Questionnaires; Treatment Outcome

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Esomeprazole; Gastroesophageal Reflux; Humans; Pantoprazole; Randomized Controlled Trials as Topic; Sulfoxides; Therapeutic Equivalency; Treatment Outcome

Resistance to proton pump inhibitors (PPI) in gastroesophageal reflux disease (GERD), which has been described in patients treated with omeprazole, could explain some exceptional cases of treatment failure and the need for surgery. The objective test of resistance to PPI is obtained with 24-hour intragastric pH-metry performed during treatment. A gastric pH of less than 4 for more than 50% of recording time indicates resistance. We present a patient with non-erosive GERD and treatment failure to omeprazole and proven resistance to esomeprazole which, to our knowledge, has only been reported in patients with Barrett's esophagus.

Topics: Adult; Anti-Ulcer Agents; Esomeprazole; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Omeprazole; Proton Pump Inhibitors; Treatment Failure

Adequacy of acid suppression is a critical factor influencing healing in gastro-oesophageal reflux disease (GORD). The European prospective study ProGORD was set up to determine the endoscopic and symptomatic progression of GORD over five years under routine care, after initial acid suppression with esomeprazole. We report on factors influencing endoscopic healing and symptom resolution during the acute treatment phase.. Patients with symptoms suggestive of GORD underwent endoscopy and biopsies were obtained from the oesophagus for diagnosis of abnormalities, including Barrett's oesophagus (BO). Data from 6215 patients were included in the "intention to treat" analysis, 3245 diagnosed as having erosive reflux disease (ERD) and 2970 non-erosive reflux disease (NERD). ERD patients were treated with esomeprazole 40 mg for 4-8 weeks for endoscopic healing while NERD patients received 20 mg for 2-4 weeks for resolution of heartburn symptoms.. Endoscopic healing occurred overall in 87.7% of ERD patients although healing was significantly lower in those with more severe oesophagitis (76.9%) and in those with BO (72.4%), particularly in Helicobacter pylori negative BO patients (70.1%). Age, sex, and body mass index appeared to have no significant impact on healing. Complete heartburn resolution was reported by 70.4% of ERD patients and by 64.8% of NERD patients at the last visit. Only H pylori infection had a significant influence on complete heartburn resolution in the NERD group (68.1% and 63.7% for H pylori positive and H pylori negative, respectively; p = 0.03).. The presence of Barrett's mucosa, as well as severe mucosal damage, exerts a negative impact on healing. H pylori infection had a positive influence on healing in ERD patients with coexistent BO but no influence on those without BO.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antacids; Anti-Ulcer Agents; Barrett Esophagus; Biopsy; Cohort Studies; Endoscopy, Gastrointestinal; Esomeprazole; Esophagitis; Female; Gastroesophageal Reflux; Heartburn; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Treatment Outcome

Data on Asian patients who present with reflux symptoms to their primary care physicians are limited.. To determine whether empirical therapy without endoscopy is appropriate for patients who present to their primary care physicians with uninvestigated reflux symptoms without alarm symptoms.. Forty-seven patients presenting with uninvestigated, dominant reflux symptoms but without alarm features to their primary care physicians underwent endoscopy within 2 weeks of referral. Their endoscopic findings were compared with those of 162 primary care patients presenting with uninvestigated dominant dyspepsia. All patients, except those with ulcers, were treated with esomeprazole 20 mg b.d. for 2 weeks. Their treatment response was assessed at 2 weeks using a symptom score.. Among patients with dominant reflux symptoms, 14 (30%) had erosive oesophagitis. No other clinically significant endoscopic findings were detected among them. In contrast, erosive oesophagitis and peptic ulcer were found in 13 (8%, P < 0.001 vs. reflux group), and 12 (7%, P = 0.06 vs. reflux group), respectively, of patients with dominant dyspepsia. Thirty-seven of forty-five (82%) of those with dominant reflux symptoms and 109 of 139 (78%; P = N.S. vs. reflux group) of those with dominant dyspepsia reported > or = 50% resolution of symptoms after esomeprazole treatment.. Empirical proton pump inhibitor without endoscopy is reasonable for uninvestigated patients who present to primary care physicians with dominant reflux symptoms.

Topics: Adult; Aged; Anti-Ulcer Agents; Endoscopy, Gastrointestinal; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Prospective Studies; Treatment Outcome

Laryngopharyngeal reflux (LPR) is frequently treated with empiric proton-pump inhibitors (PPI), but the optimal dosing and duration is unknown. We performed an open label prospective cohort study to evaluate whether twice-daily (BID) PPI is more effective than once-daily (QD) PPI for the treatment of LPR.. Patients diagnosed with LPR based on ear, nose, and throat (ENT) symptoms and laryngoscopy findings were enrolled. Questionnaire assessed demographics, ENT symptoms, symptom severity, and exposure to other potential laryngeal irritants. Esophageal manometry, ambulatory 24-hour pH monitoring, and upper gastrointestinal endoscopy were performed before initiation of therapy. Patients were consecutively assigned to three groups: BID PPI (lansoprazole 30 mg BID), BID PPI + H2 receptor antagonist (H2RA; omeprazole 20 mg BID + ranitidine 300 mg each night), or QD PPI (esomeprazole 40 mg QD). Greater than 50% primary symptom improvement from baseline defined symptom response. At 2 month follow-up, the same PPI dose was continued for responders, and PPIs were doubled for nonresponders for an additional 2 months. Repeat symptom assessment and laryngoscopy performed at 4 month follow-up.. Eighty-five patients were enrolled (median age 49 years, interquartile range 44.0 - 65.0; 76% white; 34% male). Treatment groups were BID PPI for 30 patients, BID PPI + H2RA for 30 patients, and QD PPI for 25 patients. RESPONSE TO THERAPY: At 2 months, BID response occurred among 15 of 30 (50%) patients, BID + H2RA for 15 of 30 (50%), and QD for 7 of 25 (28%) (P = .03). No statistical difference found between the two BID PPI groups with and without H2RA. Among the QD group nonresponders, 7 of 13 (54%) achieved symptom response with additional 2 months of BID dosing. At 4 month follow-up, an additional 22% of responses were obtained from the two BID groups (43/60, 72%). The overall response rate for all three groups was 70% (54/77). PREDICTORS OF OUTCOME: Pretherapy interarytenoid mucosa and true vocal folds abnormalities were associated with twofold increase in symptom response (odds ratio 1.99 and 1.96, respectively, P = .017).. BID PPI appears to be more effective than QD PPI in achieving clinical symptom response in suspected LPR. More response was achieved at 4 months compared with 2 months. Therefore, aggressive acid suppression with BID PPI for at least 4 months is warranted for treatment of LPR.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Cohort Studies; Drug Administration Schedule; Enzyme Inhibitors; Esomeprazole; Female; Fiber Optic Technology; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Hypopharynx; Lansoprazole; Laryngoscopy; Male; Manometry; Middle Aged; Omeprazole; Predictive Value of Tests; Prospective Studies; Proton Pump Inhibitors; Severity of Illness Index; Surveys and Questionnaires; Time Factors

Gastro-esophageal reflux disease (GERD) is a common disease. It impairs health related quality of life (HRQL). However, the impact on utility scores and work productivity in patients with moderate to severe GERD is not well known.. We analyzed data from 217 patients with moderate to severe GERD (mean age 50, SD 13.7) across 17 Canadian centers. Patients completed three utility instruments--the standard gamble (SG), the feeling thermometer (FT), and the Health Utilities Index 3 (HUI 3)--and several HRQL instruments, including Quality of Life in Reflux and Dyspepsia (QOLRAD) and the Medical Outcomes Short Form-36 (SF-36). All patients received a proton pump inhibitor, esomeprazole 40 mg daily, for four to six weeks.. The mean scores on a scale from 0 (dead) to 1 (full health) obtained for the FT, SG, and HUI 3 were 0.67 (95% CI, 0.64 to 0.70), 0.76 (95% CI, 0.75 to 0.80), and 0.80 (95% CI, 0.77 to 0.82) respectively. The mean scores on the SF-36 were lower than the previously reported Canadian and US general population mean scores and work productivity was impaired.. GERD has significant impact on utility scores, HRQL, and work productivity in patients with moderate to severe disease. Furthermore, the FT and HUI 3 provide more valid measurements of HRQL in GERD than the SG. After treatment with esomeprazole, patients showed improved HRQL.

Topics: Adult; Aged; Aged, 80 and over; Enzyme Inhibitors; Esomeprazole; Gastroesophageal Reflux; Health Status; Humans; Middle Aged; Pain Measurement; Proton Pump Inhibitors; Quality of Life; Sickness Impact Profile; Work Capacity Evaluation

To study the effect of proton pump inhibitor (PPI) treatment on patients with reflux esophagitis and its in vivo effect on apoptosis, p53- and epidermal growth factor receptor (EGFR) expression.. After informed consent was obtained, gastric biopsies of the antrum were taken from patients with reflux oesophagitis prior to and after 6 mo of 20 mg omeprazole (n = 14) or 40 mg esomeprazole (n = 12) therapy. Patients did not take any other medications known to affect the gastric mucosa. All patients were Helicobacter pylori negative as confirmed by rapid urease test and histology, respectively. Cell proliferation, apoptosis, EGFR, and p53 expression were measured by immunohistochemical techniques. At least 600 glandular epithelial cells were encountered and results were expressed as percentage of total cells counted. Was considered statistically significant.. Although there was a trend towards increase of cell proliferation and EGFR expression both in omeprazole and esomeprazole treated group, the difference was not statistically significant. Neither apoptosis nor p53 expression was affected.. Long-term PPI treatment does not significantly increase gastric epithelial cell proliferation and EGFR expression and has no effect on apoptosis and p53 expression.

Topics: Adult; Apoptosis; Cell Proliferation; Epithelial Cells; ErbB Receptors; Esomeprazole; Female; Gastric Mucosa; Gastroesophageal Reflux; Humans; Male; Middle Aged; Omeprazole; Proton Pump Inhibitors; Tumor Suppressor Protein p53

Gastro-oesophageal reflux disease (GORD) is a recurring condition with many patients requiring long-term maintenance therapy. Therefore initial choice of treatment has long-term cost implications. The aim was to compare the costs and effectiveness of treatment of GORD the (unconfirmed by endoscopy) with seven proton pump inhibitors (PPIs: esomeprazole, lansoprazole (capsules and oro-dispersible tablets), omeprazole (generic and branded), pantoprazole and rabeprazole), over one year.. A treatment model was developed of 13 interconnected Markov models incorporating acute treatment of symptoms, long-term therapy and subsequent decisions to undertake endoscopy to confirm diagnosis. Patients were allowed to stop treatment or to receive maintenance treatment either continuously or on-demand depending on response to therapy. Long-term dosing schedule (high dose or step-down dose) was based on current market data. Efficacy of treatments was based on clinical trials and follow-up studies, while resource use patterns were determined by a panel of physicians.. The model predicts total expected annual costs, number of symptom-free days and quality-adjusted life-years (QALY).. Generic omeprazole and rabeprazole dominated (i.e. cost less and resulted in more symptom-free days and higher QALY gains) the other PPIs. Rabeprazole had a favourable cost-effectiveness ratio of 3.42 pounds per symptom-free day and 8308 pounds/quality-adjusted life-year gained when compared with generic omeprazole. Rabeprazole remained cost-effective independent of choice of maintenance treatment (i.e. proportion of patients remaining on continuous treatment versus on-demand treatment).. Economic models provide a useful framework to evaluate PPIs in realistic clinical scenarios. Our findings show that rabeprazole is cost-effective for the treatment of GORD.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Esomeprazole; Gastroesophageal Reflux; Humans; Lansoprazole; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Sulfoxides; United Kingdom

Gastroesophageal reflux disease (GERD), is a common disorder. The most effective medical treatment for GERD is a proton pump inhibitor (PPI). The aim of this study was to specify the most inexpensive PPI therapy for GERD, and to examine the implications of varying outcome measure, holding time, on the conclusions about the cost-effectiveness of the treatments. Proton pump inhibitors that have holding time of intragastric pH>4 for at least 11h in 24h period (esomeprazole, lansoprazole, omeprazole and rabeprazole), were included. In this cost-minimization analysis (CMA), data on holding times were gathered from scientific publications listed in MEDLINE, prices of proton pump inhibitors from the Finnish database of drug prices and the treatment dosages were taken from the official guide of drug therapies in Finland. A decision tree was applied and the probabilities utilized were acquired from three expert physicians. The cost-minimization analysis was performed in three settings. At first, drugs that had a holding time (pH>4) of 11h or more were included. Secondly, drugs that had a holding time of 12h or more were included, and thirdly, a holding time of 13h or more was required. In the first analysis, the least expensive PPI treatment was lansoprazole (average cost of 138.89 per patient). In the second analysis, least expensive treatment was rabeprazole (193.81 per patient), and in the third, rabeprazole again (193.81 per patient). Esomeprazole and omeprazole were not among two of the least expensive alternatives in any of the settings. Which proton pump therapy turns out to be the least expensive for GERD, depends on the length of the holding time desired. Varying the holding time of the drug had a profound effect on the conclusions about the cost-effectiveness of the alternative treatments.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Benzimidazoles; Cost Control; Cost-Benefit Analysis; Databases, Factual; Decision Trees; Dose-Response Relationship, Drug; Drug Administration Schedule; Enzyme Inhibitors; Esomeprazole; Gastroesophageal Reflux; Humans; Lansoprazole; Models, Economic; Omeprazole; Proton Pump Inhibitors; Rabeprazole; Treatment Outcome

The proton pump inhibitor esomeprazole comprises the S-isomer of omeprazole. An intravenous formulation of the drug has been developed for use in patients not able to take oral drugs. The level of gastric acid control was similar with intravenous and oral esomeprazole in two studies in healthy volunteers receiving 20 or 40 mg once daily for 5 days. In addition, a similar level of gastric acid control occurred with intravenous esomeprazole 40 mg administered by infusion or injection once daily for 10 days. In healthy volunteers, intravenous esomeprazole provided faster and more effective gastric acid control than intravenous pantoprazole (40 mg once daily for 5 days). In addition, control of basal and pentagastrin-stimulated gastric acid secretion was better with intravenous esomeprazole 40 mg than with intravenous omeprazole 40 mg (single-dose study). Healing rates at 4 weeks were approximate, equals 80% in a well designed study in patients with erosive oesophagitis (n = 246) who received esomeprazole 40 mg once daily intravenously (by injection or infusion) or orally. Intravenous therapy was administered for the first week, after which all patients received oral esomeprazole. Intravenous esomeprazole was generally well tolerated in patients with erosive oesophagitis, with a tolerability profile similar to that of the oral formulation.

Topics: Administration, Oral; Area Under Curve; Double-Blind Method; Drug Administration Schedule; Esomeprazole; Gastroesophageal Reflux; Humans; Inactivation, Metabolic; Infusions, Intravenous; Injections, Intravenous; Isomerism; Multicenter Studies as Topic; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome

We describe the design and report the first results of the Progression of Gastroesophageal Reflux Disease (ProGERD) study, to our knowledge the largest prospective study of GERD patients.. Patients were recruited at 1,253 centers in Germany, Austria, and Switzerland. Following an assessment of medical history, all patients were endoscoped and received esomeprazole for 2 to 8 weeks before entering the 5-year observational phase.. A total of 6,215 patients (53% male, age 54+/-14) were included. Of these patients, 46% reported at least daily symptoms, 15% were unable to work at least once during the prior year, and 71% had visited a physician due to reflux symptoms. Barrett's esophagus (BE) was found in 11% of our GERD patients. In polychotomous regression analysis, the main factors related to the occurrence of the three GERD subgroups (nonerosive, erosive disease, and BE) were age, gender, duration of GERD, body mass index (BMI), smoking, and previous PPI use. Factors associated with longer disease duration were increasing age, male gender, BMI, increasing symptom severity, presence of erosive GERD or BE, positive family history, and smoking.. The findings indicate that GERD is a great burden for patients, and has significant socioeconomic implications. The long-term follow-up period with further endoscopic and histologic evaluations, will help further our understanding of the natural course of the disease.

Topics: Adult; Age Factors; Aged; Anti-Ulcer Agents; Body Mass Index; Chronic Disease; Disease Progression; Esomeprazole; Female; Follow-Up Studies; Gastroesophageal Reflux; Gastroscopy; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Sex Factors; Smoking

Patients with gastroesophageal reflux disease may suffer from a variety of symptoms from the upper aerodigestive tract. The objective of this study was to determine the impact of dual-probe 24-hr pH monitoring in the diagnosis of reflux-related otolaryngological disorders.. Twenty-two patients with symptoms such as chronic cough, globus pharyngeus, heartburn, dysphonia and burning sensation of the tongue underwent a complete ear, nose and throat examination, 24-hr dual-probe pH monitoring, and oesophago-gastro-duodenoscopy.. pH monitoring revealed gastroesophageal (distal) reflux in all patients and pharyngeal (proximal) reflux in 21 patients. Treatment consisted of a proton pump inhibitor (esomeprazole). Within 4 weeks 68 per cent of patients had no laryngopharyngeal symptoms; within 8 weeks 95 per cent of patients were symptom-free.. Patients with atypical reflux symptoms such as hoarseness, globus sensation or throat-clearing responded well to anti-reflux treatment.

Topics: Adult; Aged; Anti-Ulcer Agents; Cough; Endoscopy, Gastrointestinal; Esomeprazole; Female; Gastroesophageal Reflux; Hoarseness; Humans; Hydrogen-Ion Concentration; Laryngeal Diseases; Male; Middle Aged; Monitoring, Ambulatory

Patients with gastroesophageal reflux disease (GERD) may suffer from a large variety of symptoms in the upper aerodigestive tract such as globus sensation, chronic cough, hoarseness and many others. Diagnosis and causal therapy may sometimes be difficult with gastroenterologic evaluation sometimes revealing no pathologic result. The objective of this study was to determine the impact of 24-hour intraesophageal pH monitoring with 2 channels (gastric and laryngeal) in the diagnosis of reflux-induced otolaryngologic disorders.. This study included 22 patients presenting to the Department of Otolaryngology with symptoms like chronic cough (n = 3), globus sensation and dysphagia (n = 11), heartburn (n = 2), hoarseness and dysphonia (n = 2) or burning sensation of the tongue (n = 1). Three patients had a pathologic formation in the glottic area (leukoplakia, granuloma, polyp). All patients underwent a otolaryngological examination, a gastroenterological investigation and a 24-hour intraesophageal pH monitoring with 2 channels.. All 22 patients showed laryngeal mucosal lesions (posterior laryngitis). The gastroenterological evaluation with esophagogastroduodenoscopy was normal in 4 cases. 13 patients showed a hiatal hernia, 4 patients were suffering from a reflux-esophagitis grade I and 2 patients from grade II. One patient had an erythema and 5 patients showed erosions of the gastric mucosa. Seven patients had more than one of the above mentioned diagnoses. Intraesophageal pH-monitoring with 2 channels over 24 hours revealed a gastroesophageal reflux of all 22 patients and a high reflux to the laryngeal level of 21 patients, probably causing laryngopharyngeal symptoms. Therapy of the patients consisted of medical antireflux treatment with proton pump inhibitor esomeprazol (Nexium, 40 mg, 1-0-0). Within 4 weeks 15 of 22 patients had no more laryngopharyngeal symptoms or at least a significant reduction.. Patients with laryngopharyngeal symptoms such as hoarseness, globus sensation or dysphagia can suffer from GERD, even if typical symptoms such as heartburn or retrosternal pain do not exist and gastroesophageal intervention reveals a normal result. The best diagnostic instrument for the diagnosis of reflux-induced otolaryngologic disorders is a 24-hour intraesophageal pH-monitoring with 2 channels (measure-points at the distal esophagus and laryngeal level). Medical antireflux treatment should consist of proton pump inhibitors (e. g. Nexium) in a dose of 40 mg per day over at least 4 weeks.

Topics: Adult; Aged; Anti-Ulcer Agents; Esomeprazole; Esophagitis, Peptic; Female; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Male; Middle Aged; Monitoring, Ambulatory; Otorhinolaryngologic Diseases; Proton Pump Inhibitors; Reproducibility of Results; Signal Processing, Computer-Assisted; Treatment Outcome

To determine the impact of gastro-oesophageal reflux disease (GERD) on the quality of life, to assess changes in the quality of life during treatment with esomeprazole and to define factors that can predict these changes.. Patients with GERD (n=6215) were included in a prospective cohort study (ProGERD). All patients underwent endoscopy and received esomeprazole. At baseline and after 2 weeks of treatment, symptoms and quality of life were assessed. Factors that influenced changes in the quality of life were determined by multiple regression analyses.. At baseline, the quality of life in GERD patients was lower than that in the general population, and was similar to that in patients after acute coronary events. No differences in symptoms or quality of life were observed between the subgroups of patients with non-erosive GERD, erosive GERD and Barrett's oesophagus. After treatment with esomeprazole, the symptoms and quality of life were improved in all subscales within 2 weeks (P<0.001). The mean score of the disease-specific quality of life instrument (Quality of Life in Reflux and Dyspepsia Patients) increased from 4.6 to 6.2 points, representing a highly relevant clinical improvement. The generic quality of life (SF-36) reached levels similar to those in the general population, but, again, no difference was found between the three different subgroups of GERD patients. The main factors associated with an improvement in the quality of life after treatment were symptom relief, severe erosive reflux disease, absence of extra-oesophageal disorders, avoidance of non-steroidal anti-inflammatory drug intake and positive Helicobacter pylori status.. GERD causes a significant impairment in the quality of life that can be attenuated or normalized within a time period as short as 2 weeks by treatment with esomeprazole. These findings were similar across the whole GERD patient spectrum.

Topics: Adult; Aged; Anti-Ulcer Agents; Cohort Studies; Esomeprazole; Esophagoscopy; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Prospective Studies; Quality of Life

Barrett's esophagus is a metaplastic condition associated with gastroesophageal reflux disease and an increased risk for adenocarcinoma. Acid plays a significant role in the development and progression of Barrett's esophagus and high dose proton pump inhibitor (PPI) therapy is often needed. The aim of this study is to assess the efficacy of esomeprazole, a new potent PPI, on symptom relief and intraesophageal and intragastric acid suppression in patients with Barrett's esophagus (BE). Patients were evaluated by standardized questionnaires and dual sensor 24-h pH monitoring while receiving esomeprazole at a dose (40-80 mg/day) needed for control of symptoms. Analyses of intraesophageal and intragastric pH profiles were then made. Thirteen patients, mostly men, were studied. All tolerated esomeprazole (40-80 mg/day) with good symptom control. Sixty-two percent of patients with BE had abnormal intraesophageal pH profiles despite adequate symptom control on esomeprazole which was associated with significant breakthrough of intraesophageal acid control, particularly at night. Low nocturnal intragastric pH correlated highly with nocturnal intraesophageal acid reflux (P = 0.004) and there was a relative failure of nocturnal intragastric acid control with esomeprazole. A high percentage of patients with BE continue to exhibit pathologic GERD and low intragastric pH despite esomeprazole for reflux symptom control. For an antisecretory treatment aimed at chemoprevention of esophageal adenocarcinoma to be effective, higher PPI dosing confirmed by pH monitoring may be necessary.

Topics: Barrett Esophagus; Esomeprazole; Esophagus; Female; Gastric Acidity Determination; Gastric Mucosa; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors

Since their introduction in the late 1980s, proton pump inhibitors have demonstrated gastric acid suppression superior to that of histamine H2-receptor blockers. Proton pump inhibitors have enabled improved treatment of various acid-peptic disorders, including gastroesophageal reflux disease, peptic ulcer disease, and nonsteroidal antiinflammatory drug-induced gastropathy. Proton pump inhibitors have minimal side effects and few significant drug interactions, and they are generally considered safe for long-term treatment. The proton pump inhibitors omeprazole, lansoprazole, rabeprazole, and the recently approved esomeprazole appear to have similar efficacy.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Benzimidazoles; Drug Interactions; Esomeprazole; Gastroesophageal Reflux; Humans; Lansoprazole; Omeprazole; Pantoprazole; Peptic Ulcer; Proton Pump Inhibitors; Rabeprazole; Sulfoxides

The aim of this study was to create a useful model of the effect of the area under the plasma concentration vs time curve (AUC) and the maximum plasma concentration (C(max)) of esomeprazole on intragastric pH, measured as the percentage of total time with intragastric pH above 4 (%pH>4) during a 24-h period.. The evaluation is based on esomeprazole data from two crossover studies. In the first study ( n=36), intragastric pH and plasma concentrations were measured on day 5 of repeated once-daily 20-mg and 40-mg doses of esomeprazole during fasting conditions. In the second study ( n=24), measurements were made on days 1 and 5 of repeated once-daily dosing with 40 mg of esomeprazole under fasting and fed conditions. A model was applied in which the logistic function of %pH>4 was assumed to be linearly dependent on log-transformed AUC and C(max). The effects of repeated dosing and of fed relative to fasting conditions were included in the model, and the interindividual variation in %pH>4 was accounted for.. The effect of the pharmacokinetic variables AUC and C(max) of esomeprazole on %pH>4 can be adequately described by a model using a logistic function for %pH>4 and a normally distributed error. In this model, log-transformed AUC and C(max) were both statistically significant. The model showed that for a fixed AUC, a decrease in C(max) gives an increase in %pH>4. A decrease in AUC, keeping C(max) fixed, gives a decrease in %pH>4, but a simultaneous decrease in C(max) and AUC will result in a less pronounced decrease in %pH>4. The model may be used for predicting differences in %pH>4 between two formulations, based on assessments of AUC and C(max). Repeated dosing gave an increased %pH>4, where approximately half of the increase stemmed from increased AUC and C(max), and the rest could be attributable to the persistent blockade of the proton pumps. Food intake reduced AUC and C(max) but had no obvious effect on %pH>4, which is explained by a prolonged time period with quantifiable plasma concentrations.. The effect of the pharmacokinetic variables AUC and C(max) of esomeprazole on %pH>4 can be adequately described by a model using a logistic function for %pH>4 and a normally distributed error.

Topics: Administration, Oral; Adult; Anti-Ulcer Agents; Area Under Curve; Circadian Rhythm; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Eating; Esomeprazole; Fasting; Female; Gastric Acid; Gastric Acidity Determination; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged

Esomeprazole is the last PPI registered on the Belgian market. It is the stable s-isomer of omeprazole. It has a better pharmacokinetic profile than omeprazole (racemate), allowing also better clinical performances. Esomeprazole is the first PPI shown superior to omeprazole in acute and chronic treatment of gastro-esophageal reflux disease. Controlled trials with this drug have also allowed to define new cost-effective strategies, such as on demand treatment for endoscopy-negative gastro-esophageal reflux and one week treatment of Helicobacter pylori positive duodenal ulcer.

Topics: Cost Control; Drug Costs; Duodenal Ulcer; Enzyme Inhibitors; Esomeprazole; Gastroesophageal Reflux; Helicobacter Infections; Humans; Omeprazole; Proton Pump Inhibitors

Topics: Anti-Ulcer Agents; Costs and Cost Analysis; Drug Approval; Drug Interactions; Duodenal Ulcer; Esomeprazole; Gastroesophageal Reflux; Humans; United States; United States Food and Drug Administration

To evaluate the cost effectiveness of on-demand treatment with esomeprazole 20mg compared with two alternative omeprazole treatment strategies for the long-term management of patients with gastro-oesophageal reflux disease (GORD) without oesophagitis.. A simple Markov model was designed to compare the cost effectiveness of on-demand esomeprazole 20mg therapy for 6 months with a strategy consisting of intermittent 4-week acute treatment courses of omeprazole 20mg once daily or a strategy consisting of continuous omeprazole treatment (20mg once daily) following acute treatment of first relapse while on no drug treatment (a commonly used conventional care strategy). Relapse probabilities were based on pooled results from two 6-month placebo-controlled clinical studies of on-demand esomeprazole 20mg treatment in patients with GORD without oesophagitis and on results from a GORD study with a 6-month untreated follow-up. The expected number of relapses per patient was used as the effectiveness measure. SETTING AND PERSPECTIVE: Patient management assumptions were based on a UK physician survey. The cost-effectiveness analysis considered UK direct medical costs from the perspective of the National Health Service.. The pooled analysis showed that after 6 months treatment, 90% of patients could control symptoms effectively with on-demand esomeprazole 20mg. The expected number of relapses per patient was estimated at 0.10 for on-demand esomeprazole, 0.57 to 1.12 for intermittent omeprazole and 0.47 to 0.75 for conventional omeprazole treatment. The esomeprazole strategy incurred considerably lower direct medical costs (16 to 61%) than either omeprazole strategy.. On-demand treatment with esomeprazole 20mg is cost effective compared with two alternative omeprazole treatment strategies in patients with GORD without oesophagitis.

Topics: Adult; Cost-Benefit Analysis; Enzyme Inhibitors; Esomeprazole; Esophagitis; Female; Gastroesophageal Reflux; Humans; Male; Markov Chains; Middle Aged; Models, Economic; Omeprazole; Proton Pump Inhibitors; United Kingdom

To evaluate the pharmacokinetics and safety of esomeprazole (Nexium), the S-isomer of omeprazole, after repeated oral dosing in patients with hepatic impairment.. Single-centre, open-label one-way study.. Twelve patients (aged 40-60 years) with mild to severe hepatic impairment received once-daily oral esomeprazole 40 mg for 5 days. Serial blood samples were drawn up to 24 h post-dose on day 5 to determine plasma levels of esomeprazole and its metabolites. Pharmacokinetic parameters were compared with an historical control group of 36 gastro-oesophageal reflux disease (GORD) patients (aged 29-58 years) with normal hepatic function.. Esomeprazole was absorbed rapidly (mean maximum plasma concentration (Cmax) 6.1 micromol/l, mean time to Cmax (tmax) 1.9 h) and eliminated rapidly (mean plasma elimination half-life (t1/2) 2.1 h). Elimination of its pharmacologically inactive sulphone and hydroxy metabolites was more gradual. Patients with mild hepatic impairment had area under the plasma concentration-time curve during the dosage interval (AUCtau) and t1/2 values largely within the range of the control group. In patients with moderate hepatic impairment, t1/2 values were similar and AUCtau was slightly higher than in controls, whereas both parameters were increased in patients with severe hepatic impairment. The mean ratios of esomeprazole AUCtau, Cmax and t1/2 values in patients with and without hepatic impairment were 1.8, 1.3 and 1.3, respectively.. The steady-state pharmacokinetics of esomeprazole were not altered substantially by mild or moderate hepatic impairment; however, plasma levels of esomeprazole were elevated in severe cases. Thus, dose adjustment appears unwarranted in mild or moderate hepatic impairment, but may be required in some severely impaired patients. Esomeprazole was tolerated well across the spectrum of hepatic impairment.

Topics: Administration, Oral; Adult; Anti-Ulcer Agents; Case-Control Studies; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Liver Cirrhosis; Male; Middle Aged

Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor to be developed as a single optical isomer. It provides better acid control than current racemic proton pump inhibitors and has a favourable pharmacokinetic profile relative to omeprazole. In large well designed 8-week trials in patients with erosive oesophagitis, esomeprazole recipients achieved significantly higher rates of endoscopically confirmed healed oesophagitis than those receiving omeprazole or lansoprazole. Esomeprazole was effective across all baseline grades of oesophagitis; notably, relative to lansoprazole, as the baseline severity of disease increased, the difference in rates of healed oesophagitis also increased in favour of esomeprazole. In two trials, 94% of patients receiving esomeprazole 40mg once daily achieved healed oesophagitis versus 84 to 87% of omeprazole recipients (20mg once daily). In a study in >5000 patients, respective healed oesophagitis rates with once-daily esomeprazole 40mg or lansoprazole 30mg were 92.6 and 88.8%. Resolution of heartburn was also significantly better with esomeprazole than with these racemic proton pump inhibitors. Long-term (up to 12 months) therapy with esomeprazole effectively maintained healed oesophagitis in these patients. Esomeprazole 20 or 40mg once daily for 4 weeks proved effective in patients with symptomatic gastro-oesophageal reflux disease (GORD) without oesophagitis. Eradicating Helicobacter pylori infection is considered pivotal to successfully managing duodenal ulcer disease. Ten days' triple therapy (esomeprazole 40mg once daily, plus twice-daily amoxicillin 1g and clarithromycin 500mg) eradicated H. pylori in 77 to 78% of patients (intention-to-treat) with endoscopically confirmed duodenal ulcer disease. Esomeprazole is generally well tolerated, both as monotherapy and in combination with antimicrobial agents. The tolerability profile is similar to that of other proton pump inhibitors. Few patients discontinued therapy because of treatment-emergent adverse events (<3% of patients) and very few (<1%) drug-related serious adverse events were reported.. Esomeprazole is an effective and well tolerated treatment for managing GORD and for eradicating H. pylori infection in patients with duodenal ulcer disease. In 8-week double-blind trials, esomeprazole effectively healed oesophagitis and resolved symptoms in patients with endoscopically confirmed erosive oesophagitis. Notably, in large (n >1900 patients) double-blind trials, esomeprazole provided significantly better efficacy than omeprazole or lansoprazole in terms of both healing rates and resolution of symptoms. Long-term therapy with esomeprazole effectively maintained healed oesophagitis in these patients. Esomeprazole was also effective in patients with symptomatic GORD. Thus, esomeprazole has emerged as an effective option for first-line therapy in the management of acid-related disorders.

Topics: Animals; Anti-Ulcer Agents; Enzyme Inhibitors; Esomeprazole; Gastroesophageal Reflux; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole; Proton Pump Inhibitors

Topics: Biological Availability; Controlled Clinical Trials as Topic; Delayed-Action Preparations; Double-Blind Method; Enzyme Inhibitors; Esomeprazole; Esophagitis; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors

Topics: Anti-Ulcer Agents; Enzyme Inhibitors; Esomeprazole; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors