indacaterol and Dyspnea

Several new fixed-dose combination bronchodilators have been recently launched, and assessing their efficacy relative to each other, and with open dual combinations is desirable. This network meta-analysis (NMA) assessed the efficacy of umeclidinium and vilanterol (UMEC/VI) with that of available dual bronchodilators in single/separate inhalers.. A systematic literature review identified randomized controlled trials of ≥10 weeks among chronic obstructive pulmonary disease patients (≥40 years), assessing the efficacy of combination bronchodilators in single or separate inhalers. Comparative assessment was conducted on change from baseline in trough forced expiratory volume in 1 second (FEV1), St George's Respiratory Questionnaire (SGRQ) total scores, transitional dyspnea index (TDI) focal scores, and rescue medication use at 12 weeks and 24 weeks using an NMA within a Bayesian framework.. A systematic literature review identified 77 articles of 26 trials comparing UMEC/VI, indacaterol/glycopyrronium (QVA149), formoterol plus tiotropium (TIO) 18 μg, salmeterol plus TIO, or indacaterol plus TIO, with TIO and placebo as common comparators at 12 weeks and approximately 24 weeks. The NMA showed that at 24 weeks, efficacy of UMEC/VI was not significantly different compared with QVA149 on trough FEV1 (14.1 mL [95% credible interval: -14.2, 42.3]), SGRQ total score (0.18 [-1.28, 1.63]), TDI focal score (-0.30 [-0.73, 0.13]), and rescue medication use (0.02 [-0.27, 0.32]); compared with salmeterol plus TIO on trough FEV1 (67.4 mL [-25.3, 159.4]), SGRQ total score (-0.11 [-1.84, 1.61]), and TDI focal score (0.58 [-0.33, 1.50]); and compared with formoterol plus TIO 18 μg on SGRQ total score (-0.68 [-1.77, 0.39]). Results at week 12 were consistent with week 24 outcomes. Due to lack of availability of evidence, no comparison was made with formoterol plus TIO on FEV1 or TDI at 24 weeks.. UMEC/VI has comparable efficacy to other dual-bronchodilator combinations on available efficacy endpoints.

Topics: Bronchodilator Agents; Drug Combinations; Drug Therapy, Combination; Dyspnea; Forced Expiratory Volume; Formoterol Fumarate; Glycopyrrolate; Humans; Indans; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Tiotropium Bromide; Treatment Outcome

We investigated the effects of indacaterol on cough and phlegm in patients with stable chronic obstructive pulmonary disease (COPD). We performed a meta-analysis with five randomized controlled trials (RCTs) of indacaterol in stable COPD patients. The symptom severity was defined using the St. George's Respiratory Questionnaire (SGRQ). We analyzed patients treated with 150 µg (n = 945) and 300 µg (n = 832) out of 3,325 patients who completed the SGRQ from five RCTs. After a 12-week treatment of 150 µg indacaterol, cough improvement was reported in 36.5% (316/866) of patients treated with indacaterol vs. 32.2% (259/804) patients treated with placebo (Relative Ratio [RR], 1.13; 95% confidence interval [CI], 0.99-1.29). Phlegm improvement was reported in 31.0% (247/798) of patients treated with indacaterol vs. 30.6% (225/736) of patients treated with placebo (RR, 1.01; 95% CI, 0.87-1.18). Dyspnea improvement was reported in 39.5% (324/820) of patients treated with indacaterol vs. 31.5% (237/753) patients treated with placebo (RR, 1.33; 95% CI, 1.03-1.71; P = 0.001, I(2) = 55.1%). Only dyspnea improvement was significant compared to placebo even at the 300 µg indacaterol dose. Compared to placebo, a 12-week treatment of the long-acting beta-agonist, indacaterol might not have a significant effect on cough or phlegm in stable COPD.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Bronchodilator Agents; Cough; Dyspnea; Forced Expiratory Volume; Humans; Indans; Placebos; Pulmonary Disease, Chronic Obstructive; Quinolones; Sputum; Surveys and Questionnaires; Treatment Outcome

Chronic obstructive pulmonary disease (COPD) is a common disease in the general population and it places a considerable burden on patients, with the disease negatively affecting quality of life. In practice, patients with COPD generally seek medical attention because of symptoms, particularly breathlessness, and the resulting physical limitations, which affect the health-related quality of life (HR-QOL) in patients. The defining feature of COPD is airflow limitation that causes air trapping and increased hyperinflation as the ventilation rate increases during physical effort. Hyperinflation causes or worsens breathlessness as breathing becomes inefficient, with the end result being an avoidance of physical exertion and a cycle of increasing dyspnea caused by inactivity and deconditioning, with deleterious effects on HR-QOL. Current published guidelines for COPD state that the goals of pharmacologic therapy should be to control symptoms, improve health status and exercise tolerance, and reduce the frequency of COPD exacerbations. Effective and sustained bronchodilation has emerged as a key strategy for improving dyspnea and ability to exercise. As there is no cure for COPD, a major goal of treatment and of research into new therapies is to improve HR-QOL in COPD patients.. More recently, indacaterol, an inhaled ultra-long-acting β(2)-agonist (24-hour action), has been approved in many countries at different doses (between 75 and 300 μg once daily) for treatment of patients with stable but symptomatic COPD. The aim of this review was to explore once-daily indacaterol clinical data as related to improvement in HR-QOL in COPD. Indacaterol studies have shown significant improvements in lung function of COPD patients, and these improvements have also translated into clinically meaningful improvements in patient symptoms and HR-QOL.

Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Bronchodilator Agents; Clinical Trials as Topic; Dyspnea; Exercise Tolerance; Humans; Indans; Pulmonary Disease, Chronic Obstructive; Quality of Life; Quinolones; Severity of Illness Index

Tiotropium bromide is an anticholinergic agent that has gained worldwide acceptance as a first-line, once daily maintenance therapy for patients with moderate-to-severe chronic obstructive pulmonary disease. The purpose of this review is to synthesize the evidence base in the past 10 years on the development of tiotropium and its efficacy compared to other able interventions such as long-acting beta agonists (LABAs), as well as to assess its safety profile and its effects on health-related outcomes in patients with COPD. Treatment with tiotropium bromide has generally improved patients' health-related quality of life, reduced the number of patients suffering from acute exacerbations, decreased the number of hospitalizations, improved dyspnea, and reduced adverse events compared to placebo. In the past decade, several studies have examined the safety and efficacy of tiotropium in comparison to placebo and to LABAs (salmeterol, formoterol, and indacaterol) over periods ranging from 3 months to 48 months of follow-up. Head-to-head comparisons of tiotropium 18μg (once daily) with salmeterol 50μg (twice daily) in well-controlled trials demonstrated that tiotropium was superior in reducing acute exacerbation events and in improving quality of life. In a few short-term studies, indacaterol was comparable to tiotropium in its efficacy in improving health-related outcomes. Although the safety record of tiotropium has been exemplary in comparison to placebo, anticholinergic events such as dry mouth can be encountered in some patients. While the long-term safety of tiotropium when delivered in the HandiHaler® has been well documented, its delivery using the Respimat® Soft Mist Inhaler™ was associated with an elevated risk of cardiovascular complications, including increased mortality when compared to placebo. The exact mechanism for this is not known but is being investigated in a large multinational study that will evaluate the long-term safety of different doses of tiotropium delivered by the Respimat® soft mist inhaler versus the HandiHaler®. Further studies are required to investigate the efficacy and safety of tiotropium in comparison with novel LABAs such as indacaterol and vilanterol, and with other emerging novel anticholinergic agents such as aclidinium bromide and NVA237 (glycopyrronium bromide).

Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Bronchodilator Agents; Dyspnea; Ethanolamines; Formoterol Fumarate; Humans; Indans; Medication Adherence; Mucociliary Clearance; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Quality of Life; Quinolones; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide

Indacaterol is a novel, once-daily (od), inhaled, long-acting β(2)-agonist bronchodilator for maintenance treatment of airflow limitation in patients with COPD. The aim of this study was to evaluate the efficacy of indacaterol on dyspnea, using available randomized placebo-controlled trials.. A systematic search was made of MEDLINE, EMBASE, the Cochrane trials databases, and a manual search of journals. Randomized placebo-controlled trials of 12 weeks or more comparing indacaterol with placebo were reviewed, and eligible studies were included in a meta-analysis. The odds ratio (OR) for likelihood of achieving TDI score ≥ 1 after 12 weeks of treatment was used as an outcome measure to compare indacaterol to placebo.. Six trials were included in the analysis. Relative to placebo, the overall ORs for response were: indacaterol 75 μg od 1.784 (95% CI 1.282 to 2.482); indacaterol 150 μg od 2.149 (95% CI 1.746 to 2.645); and indacaterol 300 μg od 2.458 (95% CI 2.010 to 3.006). Overall OR for response in TDI tended to increase with higher indacaterol doses.. Patients receiving indacaterol had clinically significant improvements in symptoms of dyspnea compared to placebo. Incremental benefits in TDI were observed with increasing doses. Indacaterol may provide patients and physicians with a useful treatment option in symptomatic patients with dyspnea.

Topics: Adrenergic beta-2 Receptor Agonists; Dyspnea; Humans; Indans; Placebos; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic

Indacaterol is a once-daily, long-acting β(2)-agonist bronchodilator that improves dyspnoea and health status in patients with moderate-to-severe COPD. While its bronchodilator effects have been shown to be maintained in different patient subgroups, effects on clinical outcomes in certain subgroups are not yet defined.. Post-hoc analysis of pooled clinical study data to investigate efficacy and safety of indacaterol compared with placebo and other long-acting bronchodilators (formoterol, salmeterol, open-label tiotropium) in patient subgroups defined by COPD severity (GOLD stage II or III; n = 4082) and ICS use at baseline (no/yes; n = 4088). Efficacy outcomes were trough (24-h post-dose) FEV(1), dyspnoea (transition dyspnoea index; TDI) and health status (St George's Respiratory Questionnaire; SGRQ) after 26 weeks.. All active treatments significantly improved trough FEV(1) and dyspnoea compared with placebo, and all apart from open-label tiotropium improved health status compared with placebo. Among active treatments, indacaterol 150 μg had the best overall efficacy profile in the GOLD II and no-ICS subgroups. In the GOLD III and ICS subgroups, indacaterol 300 μg had the best overall efficacy, including a marked effect on dyspnoea (1.4-point improvement in TDI total score vs. placebo; p < 0.001). Within subgroups, the incidence of adverse events was similar between treatments.. Indacaterol maintained its efficacy regardless of disease severity or use of concurrent ICS. Indacaterol 150 μg had the best overall efficacy profile in the GOLD stage II patients while, in patients with more severe disease, indacaterol 300 μg provided useful improvements in dyspnoea.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Albuterol; Bronchodilator Agents; Drug Administration Schedule; Drug Therapy, Combination; Dyspnea; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Indans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Scopolamine Derivatives; Severity of Illness Index; Tiotropium Bromide; Treatment Outcome; Vital Capacity

The purpose of this study was to update our network meta-analysis in order to compare the efficacy of indacaterol 75 μg with that of a fixed-dose combination of formoterol and budesonide (FOR/BUD) and a fixed-dose combination salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on evidence identified previously in addition to two new randomized clinical trials.. Fifteen randomized, placebo-controlled clinical trials including COPD patients were evaluated: indacaterol 75 μg once daily (n = 2 studies), indacaterol 150 μg once daily (n = 5), indacaterol 300 μg once daily (n = 4), FOR/BUD 9/160 μg twice daily (n = 2), FOR/BUD 9/320 μg twice daily (n = 2), SAL/FP 50/500 μg twice daily (n = 4), and SAL/FP 50/250 μg twice daily (n = 1). All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained. Treatment-by-covariate interactions were included where possible to improve the similarity of the trials. Outcomes of interest were trough forced expiratory volume in 1 second (FEV(1)) and transitional dyspnea index at 12 weeks.. Based on the results without adjustment for covariates, indacaterol 75 μg resulted in a greater improvement in FEV(1) at 12 weeks compared with FOR/BUD 9/160 μg (difference in change from baseline 0.09 L [95% credible interval 0.04-0.13]) and FOR/BUD 9/320 μg (0.07 L [0.03-0.11]) and was comparable with SAL/FP 50/250 μg (0.00 L [-0.07-0.07]) and SAL/FP 50/500 μg (0.01 L [-0.04-0.05]). For transitional dyspnea index, data was available only for indacaterol 75 μg versus SAL/FP 50/500 μg (-0.49 points [-1.87-0.89]).. Based on results of a network meta-analysis with and without covariates, indacaterol 75 μg is expected to be at least as efficacious as FOR/BUD (9/320 μg and 9/160 μg) and comparable with SAL/FP (50/250 μg and 50/500 μg) in terms of lung function. In terms of breathlessness (transitional dyspnea index) at 12 weeks, the results are inconclusive given the limited data.

Topics: Albuterol; Androstadienes; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Therapy, Combination; Dyspnea; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Indans; Outcome Assessment, Health Care; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic

The purpose of this study was to evaluate the correlation between immediate responsiveness with the short-acting β. The REVERBREZ study was a phase IV, multicentre, open-label study in which patients with moderate-to-severe COPD received indacaterol 150 μg once-daily for 5 months. The primary endpoint was the correlation between immediate response of forced expiratory volume in 1 s (FEV. Of the 602 patients enrolled from 177 centres in France, 543 patients received at least one indacaterol dose, 512 patients completed 1 month of indacaterol treatment (primary endpoint), and 400 patients completed 5 months of treatment. At study entry, mean FEV. Immediate FEV. ClinicalTrials.gov: NCT01272362 . Date: January 5, 2011.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Dose-Response Relationship, Drug; Dyspnea; Female; Forced Expiratory Volume; France; Humans; Indans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Quinolones; Vital Capacity

COPD is often associated with cardiovascular comorbidity. Treatment guidelines recommend therapy with bronchodilators as first choice. We investigated the acute effect of single-dose indacaterol on lung hyperinflation in COPD subjects, for the first time evaluating the potential effects on right heart performance.. In this Phase IV, randomized, interventional, double-blind, crossover clinical study, we recruited 40 patients (50-85 years of age) with stable COPD. Patients were treated with 150 μg indacaterol or placebo and after 60 minutes (T60) and 180 minutes (T180) the following tests were performed: trans-thoracic echocardiography (TTE), plethysmography, diffusing capacity of the lung for carbon monoxide, saturation of peripheral oxygen, and visual analog scale dyspnea score. Patients underwent a crossover re-challenge after a further 72 hours of pharmacological washout. All TTE measurements were conducted blindly by the same operator and further interpreted by two different blinded operators. Consensus decisions were taken on every value and parameter. The primary outcome was the effect of the reduction of residual volume and functional residual capacity on right heart systolic and diastolic function indexes evaluated by TTE in patients treated with indacaterol, as compared to placebo.. Vital capacity, inspiratory capacity, and forced expiratory volume in 1 second were significantly increased by indacaterol, when compared with placebo, while residual volume, intrathoracic gas volume, and specific airway resistance were significantly reduced in patients treated with indacaterol. Tricuspid annular plane systolic excursion was significantly increased versus placebo, paralleled by an increase of tricuspid E-wave deceleration time. The cardiac frequency was also significantly reduced in indacaterol-treated patients.. Indacaterol significantly reduces lung hyperinflation in acute conditions, with a clinically relevant improvement of dyspnea. These modifications are associated with a significant increase of the right ventricular compliance indexes and may have a role in improving left ventricular preload leading to a reduction in cardiac frequency.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Aged, 80 and over; Airway Resistance; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Dyspnea; Echocardiography; Female; Forced Expiratory Volume; Humans; Indans; Inspiratory Capacity; Lung Volume Measurements; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Quinolones; Treatment Outcome

In COPD patients, reversibility is currently evaluated from the changes of forced expiratory volume at 1s (ΔFEV1) and forced vital capacity (ΔFVC). By lowering peripheral airway smooth muscle tone, bronchodilators should decrease dynamic hyperinflation, gas trapping, and possibly dyspnea at rest. Hence, we hypothesize that specific airway resistance changes (ΔsRAW) should better characterize the acute response to bronchodilators.. On two days, 60 COPD patients underwent dyspnea evaluation (VAS score) and pulmonary function testing at baseline and one hour after placebo or 300μg indacaterol administration.. Spirographic and ΔsRAW-based criteria identified as responders 24 and 45 patients, respectively. ΔsRAW correlated with changes of intrathoracic gas volume (ΔITGV) (r=0.61; p<0.001), residual volume (ΔRV) (r=0.60; p<0.001), ΔFVC (r=0.44; p=0.001), and ΔVAS (r=0.73; p<0.001), while ΔFEV1 correlated only with ΔFVC (r=0.34; p=0.008). Significant differences in terms of ΔITGV (p=0.002), ΔRV (p=0.023), and ΔVAS (p<0.001) occurred only if patients were stratified according to ΔsRAW.. In assessing the acute functional effect of bronchodilators, ΔsRAW-based criterion is preferable to FEV1-FVC-based criteria, being more closely related to bronchodilator-induced improvements of lung mechanics and dyspnea at rest.

Topics: Adrenergic beta-Agonists; Aged; Airway Resistance; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Dyspnea; Female; Humans; Indans; Lung Volume Measurements; Male; Plethysmography; Pulmonary Disease, Chronic Obstructive; Quinolones; Respiratory Function Tests; Time Factors; Treatment Outcome

Chronic obstructive pulmonary disease (COPD) is a progressive, inflammatory condition, involving airways and lung parenchyma. The disease leads to airflow limitation, and pulmonary hyperinflation, resulting in dyspnea, decreased exercise tolerance, and impaired quality of life. COPD pharmacotherapy guidelines are based on a combination of long-acting beta2-agonists (LABA), long-acting antimuscarinic agents (LAMA) and methyloxantins. Recently, indacaterol, ultralong acting beta2-agonist, has been introduced. The aim of our study was to assess the impact of indacaterol add-on therapy on lung function, exercise tolerance and quality of life of COPD patients. Thirty four COPD patients, receiving stable bronchodilator therapy were randomly allocated into two arms of add-on treatment (1:1 - indacaterol:placebo) for 3 months. Indacaterol replaced LABA in all patients receiving LABA. Spirometry, lung volumes, DLCO, St George's Respiratory Questionnaire (SGRQ) and 6 min Walk Distance (6MWD) were performed before and after therapy. We found that in the indacaterol group FEV1 did not changed significantly. However, there were significant improvements in ERV, 6MWD, and 6MWD-related dyspnea score. We also found that the degree of desaturation before and after 6MWD, and fatigue levels significantly improved in the indacaterol group. The patients' quality of life also changed favorably in the indacaterol treatment arm. We conclude that the add-on therapy with indacaterol exerts positive effects in COPD patients.

Topics: Adrenergic beta-2 Receptor Agonists; Aged; Bronchodilator Agents; Dyspnea; Exercise; Exercise Tolerance; Female; Forced Expiratory Volume; Humans; Indans; Lung; Male; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation; Quality of Life; Quinolones; Receptors, Adrenergic, beta-2; Respiratory Function Tests; Surveys and Questionnaires

Indacaterol is an inhaled, once-daily, long-acting ®(2)-agonist for the treatment of COPD. Most previous studies were conducted with doses of 150 and/or 300 μg once-daily, and data with the 75 μg dose are limited. Two identically designed studies were, therefore, conducted to evaluate the efficacy and safety of the 75 μg once-daily dose. In two double-blind studies conducted in the USA, patients with moderate-to-severe COPD were randomized to treatment with indacaterol 75 μg once-daily (n = 163 and 159) or matching placebo (n = 160 and 159) for 12 weeks. The primary variable was forced expiratory volume in 1 s measured 24 h post-dose after 12 weeks (reported elsewhere). This report describes secondary efficacy endpoints, including transition dyspnea index (TDI) and St George's Respiratory Questionnaire (SGRQ) total scores, and the percentages of patients with improvements of or above the minimal clinically important difference (MCID; ≥1 in TDI score and ≥4 in SGRQ score). Differences between indacaterol and placebo for TDI total score at week 12 were 1.23 (p < 0.001) and 0.45 (p = 0.16), with odds ratios for achieving the MCID of 2.19 (p = 0.002) and 1.58 (p = 0.065). SGRQ total score decreased (improved) from baseline by 5.8 and 4.9 units with indacaterol at week 12 (2.0 and 0.9 with placebo), with odds ratios for achieving the MCID of 1.80 (p = 0.024) and 1.71 (p = 0.031). Patients receiving indacaterol had statistically significant or numerical improvements in diary-derived symptom variables compared with placebo. Treatment with indacaterol 75 μg may provide useful improvements in patient-reported outcomes in patients with moderate-to-severe COPD.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Analysis of Variance; Double-Blind Method; Drug Administration Schedule; Dyspnea; Female; Forced Expiratory Volume; Health Status Indicators; Humans; Indans; Logistic Models; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Surveys and Questionnaires; Treatment Outcome

This post hoc analysis evaluated the efficacy of indacaterol, a novel inhaled once-daily long-acting β(2)-agonist, by disease severity (GOLD 2005) in patients with moderate-to-severe COPD from six Asian countries/areas (Hong Kong, India, Japan, Korea, Singapore, Taiwan).. Data from a 12-week, double-blind, placebo-controlled, parallel-group study in patients randomized to indacaterol 150 μg, indacaterol 300 μg or placebo once daily were analyzed based on baseline disease severity (moderate or severe). Endpoints were: trough FEV(1) (average of 23 h 10 min and 23 h 45 min post-dose values), transition dyspnoea index (TDI) and St George's Respiratory Questionnaire (SGRQ) at Week 12. Safety data were collected.. Of 347 patients randomized, 59.7% had moderate, and 40.3% had severe COPD. Least squares means (LSMs) indacaterol-placebo differences in trough FEV(1) at Week 12 exceeded the pre-specified minimal clinically important difference (MCID) of 0.12L and were statistically superior (p < 0.001) for indacaterol (150 μg, 300 μg) versus placebo in the two subgroups [0.19L, 0.20L (moderate); 0.15L, 0.19L (severe) respectively]. LSM TDI scores for both indacaterol doses versus placebo in both subgroups were statistically superior (p < 0.05) and clinically meaningful (≥1 unit). Both indacaterol doses showed improvements in LSM SGRQ total scores at Week 12 which exceeded the MCID (4 units) versus placebo in both subgroups, with indacaterol 300 μg-placebo difference in the severe subgroup being statistically significant (p < 0.01). Overall incidence of adverse events was lower with indacaterol than with placebo across both subgroups.. Indacaterol demonstrated clinically relevant improvements versus placebo in lung function, dyspnea and health status in Asian COPD patients irrespective of disease severity.. NCT00794157.

Topics: Adult; Aged; Asia; Bronchodilator Agents; Double-Blind Method; Dyspnea; Female; Forced Expiratory Volume; Health Status; Humans; Indans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Sleep Wake Disorders; Treatment Outcome; Vital Capacity

Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β(2)-agonist bronchodilator recently approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the efficacy and safety of indacaterol compared with placebo and the twice-daily β(2)-agonist, salmeterol, as an active control. Patients with moderate-to-severe COPD were randomised to 6 months double-blind treatment with indacaterol (150 μg once daily), salmeterol (50 μg twice daily) or placebo. The primary efficacy end-point was trough (24 h post-dose) forced expiratory volume in 1 s (FEV(1)) after 12 weeks. 1,002 patients were randomised and 838 (84%) completed the study. Indacaterol increased trough FEV(1) at week 12 by 170 mL over placebo (p<0.001) and by 60 mL over salmeterol (p<0.001). Both active treatments improved health status (St George's Respiratory Questionnaire) and dyspnoea (transition dyspnoea index) compared with placebo, with differences between them favouring indacaterol. Safety profiles were similar across the treatment groups, and both indacaterol and salmeterol were well tolerated. Once-daily treatment with 150 μg indacaterol had a significant and clinically relevant bronchodilator effect over 24 h post-dose and improved health status and dyspnoea to a greater extent than twice-daily 50 μg salmeterol. Indacaterol should prove a useful additional treatment for patients with COPD.

Topics: Adrenal Cortex Hormones; Aged; Albuterol; Bronchodilator Agents; Drug Administration Schedule; Dyspnea; Female; Health Status; Humans; Indans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Respiratory Function Tests; Salmeterol Xinafoate; Smoking; Surveys and Questionnaires

Indacaterol is a novel, inhaled, ultra-long-acting β(2)-agonist bronchodilator for maintenance use in patients with COPD. The aim of this paper is to assess the effect of indacaterol on dyspnoea and health status, using pooled study data to evaluate the relative efficacy of indacaterol and existing bronchodilators.. Individual patient data were pooled from three randomized, placebo-controlled studies (NCT00393458; NCT00567996; NCT00463567), conducted in patients with moderate-to-severe COPD. Treatments were double-blind indacaterol 150 μg (n = 746) or 300 μg (n = 853) once-daily, formoterol 12 μg twice-daily (n = 556), salmeterol 50 μg twice-daily (n = 333) and placebo (n = 1185); and open-label tiotropium 18 μg once-daily (n = 415). Evaluation after 6 months' treatment was by transition dyspnoea index (TDI; minimum clinically important difference [MCID] ≥1 point), and St George's Respiratory Questionnaire (SGRQ; MCID ≥4 units).. Differences from placebo in TDI total score were 1.01 (indacaterol 150 μg) 1.28 (indacaterol 300 μg), 0.74 (formoterol), 0.92 (salmeterol) and 0.88 (tiotropium) (all p < 0.05), with corresponding odds ratios versus placebo for exceeding the MCID from baseline of 1.91, 2.69, 2.02, 1.79 and 1.49 (all p < 0.05). Differences versus placebo in SGRQ total score were -4.4 (indacaterol 150 μg), -3.4 (indacaterol 300 μg), -2.8 (formoterol), -4.0 (salmeterol) and -1.7 (tiotropium) (all p < 0.05), with corresponding odds ratios versus placebo for exceeding the MCID of 1.95, 1.63, 1.54, 1.82 and 1.29 (all p < 0.05 apart from tiotropium).. Indacaterol provided clinically important improvements in dyspnoea and health status that were at least as good as and often better than those observed with existing bronchodilator treatments for COPD.

Topics: Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Double-Blind Method; Dyspnea; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Health Status; Humans; Indans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Salmeterol Xinafoate

Indacaterol is a novel, inhaled once-daily ultra long-acting β2-agonist for the treatment of COPD. This randomised, double-blind, placebo-controlled, two-period crossover study evaluated the effect of two-week treatment with indacaterol 300 μg on peak and isotime exercise inspiratory capacity (IC) in patients with COPD. Patients (40-80 years) with post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 70%, percent predicted FEV1 ≥ 40% and ≤ 80%, smoking history ≥ 20 pack-years and functional residual capacity > 120% of predicted normal were randomised to receive indacaterol 300 μg or placebo once-daily via a single-dose dry powder inhaler. Following 14 days of treatment, IC at peak and isotime during constant-load (80% of maximum workload) cycle ergometry was analysed using linear mixed-effects models. Safety and tolerability were also monitored. Twenty-seven patients (67% male; mean age, 61.3 years) were randomised; 24 completed the study. On Day 14, indacaterol showed statistically significant improvements over placebo in peak (317 mL [95% CI: 118-517]; p < 0.01) and isotime IC (268 mL [95% CI: 104-432]; p < 0.01). Statistically significant improvements were observed with indacaterol versus placebo on Day 14 for the following secondary endpoints: resting IC, trough FEV1, dyspnoea (BDI/TDI and Borg CR10 scale at isotime) and exercise endurance time. Indacaterol was well tolerated, with no serious adverse events or deaths. In conclusion, indacaterol 300 μg administered once-daily showed a clinically relevant increase in IC after 14 days of treatment, reflecting a reduction in dynamic hyperinflation.

Topics: Adrenergic beta-2 Receptor Agonists; Aged; Cross-Over Studies; Double-Blind Method; Dyspnea; Exercise Tolerance; Female; Forced Expiratory Volume; Humans; Indans; Inspiratory Capacity; Linear Models; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Treatment Outcome

Indacaterol is the first once-daily, long-acting inhaled beta(2)-agonist bronchodilator studied in patients with chronic obstructive pulmonary disease (COPD).. To demonstrate greater efficacy of indacaterol versus placebo on FEV(1) at 24 hours post dose (trough) after 12 weeks, to compare efficacy with placebo and tiotropium, and to evaluate safety and tolerability over 26 weeks.. Patients with moderate-to-severe COPD were randomized to double-blind indacaterol 150 or 300 microg or placebo, or open-label tiotropium 18 microg, all once daily, for 26 weeks. The primary efficacy outcome was trough FEV(1) at 12 weeks. Additional analyses (not adjusted for multiplicity) included transition dyspnea index (TDI), health status (St George's Respiratory Questionnaire [SGRQ]), and exacerbations. Serum potassium, blood glucose, and QTc interval were measured.. A total of 1,683 patients (age, 63.3 yr; post-bronchodilator FEV(1), 56% predicted; FEV(1)/FVC, 0.53) were randomized to the four treatment arms. Trough FEV(1) at Week 12 increased versus placebo by 180 ml with both indacaterol doses and by 140 ml with tiotropium (all P < 0.001 vs. placebo). At Week 26, for indacaterol 150/300 microg, respectively, versus placebo, TDI increased (1.00/1.18, P < 0.001) and SGRQ total score decreased (-3.3/-2.4, P < 0.01); corresponding results with tiotropium were 0.87 (P < 0.001) for TDI and (-1.0, P = not significant) for SGRQ total score. The incidence of adverse events, low serum potassium, high blood glucose, and prolonged QTc interval was similar across treatments.. Indacaterol was an effective once-daily bronchodilator and was at least as effective as tiotropium in improving clinical outcomes for patients with COPD. Clinical trial registered with clinicaltrials.gov (NCT 00463567).

Topics: Administration, Inhalation; Blood Glucose; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Dyspnea; Electrocardiography; Female; Forced Expiratory Volume; Health Status; Humans; Indans; Male; Middle Aged; Potassium; Pulmonary Disease, Chronic Obstructive; Quinolones; Scopolamine Derivatives; Spirometry; Tiotropium Bromide

Although the prevalence of chronic obstructive pulmonary disease (COPD) increases with age, no specific therapeutic approaches are available till date for the elderly population.. To assess the efficacy and safety of once-daily indacaterol 150 and 300 μg in elderly patients with moderate to severe COPD.. Data were pooled from 11 randomized, double-blind, placebo- and active-controlled studies (8445 patients with COPD). The patient population was stratified into age groups: young (≥40-<65 years; 52.3%), elderly (≥65-<75 years; 36.4%), and very elderly (≥75 years; 11.4%). The efficacy outcomes included improvements in trough forced expiratory volume in 1 s (FEV. At Week 12, the mean improvement in FEV. This pooled analysis suggests that the efficacy and safety of indacaterol treatment is similar between elderly and younger patients with COPD.

Topics: Adrenergic beta-2 Receptor Agonists; Aged; Aged, 80 and over; Bronchodilator Agents; Clinical Trials, Phase III as Topic; Double-Blind Method; Dyspnea; Female; Forced Expiratory Volume; Formoterol Fumarate; Health Status; Humans; Indans; Male; Middle Aged; Netherlands; Prevalence; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Severity of Illness Index; Smoking; Tiotropium Bromide; Treatment Outcome; Vital Capacity

Guidelines for chronic obstructive pulmonary disease (COPD) recommend that treatment choices be based partly on symptoms.. A post-hoc analysis of pooled data from clinical studies compared the efficacy and safety of once-daily inhaled bronchodilators indacaterol (150 and 300 μg) and open-label tiotropium (18 μg) according to baseline dyspnoea severity on the modified Medical Research Council (mMRC) scale in patients with COPD (mMRC scores <2 = 'less dyspnoea'; scores ≥2 = 'more dyspnoea'). Outcomes were assessed after 26 weeks.. The analysis included 3177 patients. In patients with less dyspnoea: indacaterol (both doses) improved 24-h post-dose ('trough') forced expiratory volume in 1 s (FEV1), transition dyspnoea index (TDI) and St George's Respiratory Questionnaire (SGRQ) total scores at week 26 and reduced the risk of COPD exacerbations vs placebo; and open-label tiotropium improved trough FEV1 and TDI total score vs placebo at week 26. In patients with more dyspnoea: indacaterol (both doses) improved trough FEV1, TDI and SGRQ total scores at week 26; indacaterol 300 μg was the only treatment to improve the TDI total score by more than the minimum clinically important difference (≥1 point) vs placebo; and open-label tiotropium improved trough FEV1, TDI total score at week 26 and decreased the risk of COPD exacerbations vs placebo. In both subgroups, all treatments were well tolerated.. In patients with less dyspnoea, all treatments had similar effects. Indacaterol 300 μg may be a useful treatment option for patients with COPD who experience more severe breathlessness.

Topics: Bronchodilator Agents; Delayed-Action Preparations; Dose-Response Relationship, Drug; Dyspnea; Forced Expiratory Volume; Humans; Indans; Patient Acuity; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic; Scopolamine Derivatives; Tiotropium Bromide

Once-daily long-acting β2-agonists (LABAs) are an important treatment option, either alone or in combination with other inhaled long-acting bronchodilators in the management of chronic obstructive pulmonary disease (COPD).. To audit the effectiveness of indacaterol as maintenance therapy in patients with moderate-to-severe COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] stage II/III).. This was a single-center audit of a primary care COPD cohort comprising all patients treated with indacaterol following treatment escalation (as per National Institute for Health and Care Excellence guidelines) or failure with other therapies. The sample was restricted to patients treated for a minimum of 12 months with indacaterol, for whom preswitching and follow-up spirometry as well as exacerbation frequency data were available (GOLD spirometry guidelines). Pulmonary function was assessed by spirometry (recorded as forced expiratory volume in 1 second [FEV1] expressed as percentage predicted). Relevant self-reported qualitative information was recorded in descriptive terms for quality of life (QoL) assessment.. A total of 15 patients met the audit inclusion criteria (66.6% male, mean age 64.9±7.7 years). COPD disease duration ranged from 1 to 22 years; 93% had GOLD stage II or III COPD. Follow-up ranged in duration from 12 to 27 months. Indacaterol was associated with a significant reduction in exacerbation frequency compared with the 12 months prior to initiation (P=0.02). In those patients who experienced three or more exacerbations/year, mean exacerbation rate fell from 5.43±1.07 to 2.43±0.2 after 12 months treatment with indacaterol (P=0.02). A reduction in dyspnea was noted in 53% of patients. Similarly, improvements in exercise tolerance and well-being were self-reported in 67% and 93%, respectively.. Indacaterol was found to be an effective LABA as an escalation or switch medication in patients with moderate-to-severe COPD. Indacaterol was effective both as monotherapy and in combination with a long-acting muscarinic antagonist. Switching to indacaterol from a LABA/inhaled corticosteroid fixed-combination inhaler significantly reduced the number of acute exacerbations and also improved self-reported QoL.

Topics: Adrenergic beta-2 Receptor Agonists; Aged; Bronchodilator Agents; Drug Substitution; Drug Therapy, Combination; Drug Utilization Review; Dyspnea; England; Exercise Tolerance; Female; Forced Expiratory Volume; Humans; Indans; Lung; Male; Medical Audit; Middle Aged; Muscarinic Antagonists; Primary Health Care; Pulmonary Disease, Chronic Obstructive; Quality of Life; Quinolones; Retrospective Studies; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Treatment Outcome