tiotropium-bromide and Cystic-Fibrosis

Topics: Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Cystic Fibrosis; Forced Expiratory Volume; Humans; Muscarinic Antagonists; Tiotropium Bromide

Cystic fibrosis is a life-limiting inherited condition which affects one in 2500 newborns in the UK and 70,000 children and adults worldwide. The condition is multifaceted and affects many systems in the body. The respiratory system is particularly affected due to a build up of thickened secretions and a predisposition to infection. Inhaled bronchodilators are prescribed for 80% of people with cystic fibrosis in order to widen the airways and alleviate symptoms. Both short- and long-acting inhaled bronchodilators are used to improve respiratory symptoms. Short-acting inhaled bronchodilators take effect in minutes and typically last for four to eight hours (muscarinic antagonists). Long-acting inhaled bronchodilators also take effect within minutes but typically last for around 12 hours and sometimes longer. This review is one of two which are replacing a previously published review of both long- and short-acting inhaled bronchodilators.. This review aims to evaluate long-acting inhaled bronchodilators in children and adults with cystic fibrosis in terms of clinical outcomes and safety. If possible, we aimed to assess the optimal drug and dosage regimen.. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search: 10 October 2017.We also carried out a separate search of Embase and the reference lists of included trials. We searched clinical trials registries for any ongoing trials and made contact with pharmaceutical companies for any further trials.Date of Embase search: 11 October 2017.. Randomised or quasi-randomised parallel trials comparing long-acting inhaled bronchodilators (beta-2 agonists and muscarinic antagonists) with placebo, no treatment or a different long-acting inhaled bronchodilator in adults and children with cystic fibrosis.. Both authors independently assessed trials for inclusion (based on title, abstract and full text). The authors independently assessed the included trials for quality and risk of bias and extracted data. Discrepancies were resolved by a third party.. The searches identified 195 unique references, of which 155 were excluded on title and abstract. We assessed the full texts of the remaining references, excluded 16 trials (28 references) and included four trials (12 references) in the review with 1082 participants.One trial (n = 16) measuring the effect of beta-2 agonists reported an improvement in forced expiratory volume at one second (FEV. Neither long-acting beta-2 agonists nor long-acting muscarinic antagonist bronchodilators demonstrate improvement in our primary outcome of FEV

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Cystic Fibrosis; Disease Progression; Forced Expiratory Volume; Humans; Muscarinic Antagonists; Quality of Life; Randomized Controlled Trials as Topic; Time Factors; Tiotropium Bromide

People with cystic fibrosis (CF) suffer from chronic lung disease that is often treated with a bronchodilator. This trial evaluated the pharmacokinetics, safety, and tolerability of single and multiple doses of tiotropium inhaled via the Respimat® Soft Mist™ Inhaler in patients with CF.. Patients received a single dose (placebo, 2.5 μg, 5 μg, or 10 μg) and/or multiple doses (placebo, 2.5 μg, or 5 μg) of tiotropium daily for 28 days.. Ninety-two patients, aged 5-57 years, were treated. All doses showed a satisfactory safety profile for adverse events, vital signs, laboratory evaluations, and physical examination. At steady-state, peak exposure to tiotropium was comparable between adult patients with CF and patients with chronic obstructive pulmonary disease.. Tiotropium 2.5 μg or 5 μg inhaled via the Respimat® Soft Mist™ Inhaler once daily was well tolerated in patients with CF.

Topics: Administration, Inhalation; Adolescent; Adult; Age Factors; Bronchodilator Agents; Child; Child, Preschool; Cholinergic Antagonists; Cystic Fibrosis; Double-Blind Method; Drug Administration Schedule; Drug Monitoring; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Tiotropium Bromide; United States; Young Adult

Tiotropium Respimat improved lung function in a phase 2 trial in patients with cystic fibrosis (CF). We investigated its efficacy and safety in a phase 3 trial, including a pre-specified pooled analysis of the phase 2 and 3 trials.. 12-week, randomized, double-blind, placebo-controlled trial of tiotropium Respimat 5 μg once daily in patients with CF (N=463).. Co-primary efficacy endpoints showed no statistical difference between tiotropium and placebo: percent-predicted forced expiratory volume in 1s (FEV1) area under the curve from 0-4h (AUC0-4h) (95% CI): 1.64% (0.27,3.55; p=0.092); percent-predicted trough FEV1 (95% CI) 1.40% (0.50,3.30; p=0.15). Adverse events were similar between groups. Pooled phase 2/3 trial results showed a treatment difference in favor of tiotropium: percent-predicted FEV1 AUC0-4h (95% CI): 2.62% (1.34,3.90).. Tiotropium was well tolerated in patients with CF; lung function improvements compared with placebo were not statistically significant in the phase 3 trial.. These studies are registered with clinical trial identifier numbers NCT00737100 and NCT01179347 NCT00737100 NCT01179347. These studies are also registered with the EudraCT number: 2008-001156-43 and 2010-019802-17.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Child; Child, Preschool; Cholinergic Antagonists; Cystic Fibrosis; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Forced Expiratory Flow Rates; Humans; Infant; Male; Middle Aged; Tiotropium Bromide; Treatment Outcome; Young Adult

Tiotropium is the first bronchodilator to be studied systematically in cystic fibrosis (CF). We investigated whether any intrinsic or extrinsic factors affected pharmacokinetic (PK) parameters of inhaled tiotropium delivered by Respimat(®) in adults and children with CF. Tiotropium PK in patients with CF was compared with that of healthy volunteers and patients with chronic obstructive pulmonary disease (COPD). This pooled analysis summarizes the PK parameters of inhaled tiotropium Respimat(®) across 9 early- and late-phase trials involving 27 healthy volunteers (1 trial), 409 patients with CF (3 trials), and 281 patients with COPD (5 trials). Patients with CF aged 5 to 11, 12 to 17, and ≥ 18 years had similar tiotropium plasma concentrations (geometric mean C(0.083,ss,norm): 2.22 pg/mL/μg; not determined for patients aged <5 years). The fraction excreted unchanged in the urine was 3.4-fold lower for patients aged 0.4 to <5 years than for those aged 5 to 11 years (fe(0-4,ss): 1.19% vs 4.09%). Tiotropium PK parameters were similar between CF patients and COPD patients.

Topics: Adolescent; Adult; Age Factors; Aged; Bronchodilator Agents; Case-Control Studies; Child; Child, Preschool; Cystic Fibrosis; Double-Blind Method; Humans; Infant; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide; Young Adult

Tiotropium is a once-daily, long-acting anticholinergic bronchodilator with the potential to alleviate airway obstruction in cystic fibrosis. Our objective was to evaluate the efficacy and safety of 2.5 and 5 µg once-daily tiotropium delivered via the Respimat Soft Mist Inhaler vs. placebo in people with cystic fibrosis.. This phase 2, 12-week, randomized, double-blind, placebo-controlled parallel-group study of tiotropium Respimat as add-on to usual cystic fibrosis maintenance therapy included people with cystic fibrosis with pre-bronchodilator forced expiratory volume in 1 second (FEV1) ≥ 25% predicted. Co-primary efficacy end points were change from baseline in percent-predicted FEV1 area under the curve from 0 to 4 hours (FEV1 AUC0-4h), and trough FEV1 at the end of week 12.. A total of 510 subjects with cystic fibrosis aged 5-69 years were randomized. Both doses of tiotropium resulted in significant improvement compared with placebo in the co-primary efficacy end points at the end of week 12 (change from baseline in percent-predicted FEV1 AUC0-4h: 2.5 µg: 2.94%, 95% confidence interval 1.19-4.70, p = 0.001; 5 µg: 3.39%, 95% confidence interval 1.67-5.12, p = 0.0001; in percent-predicted trough FEV1 ∶ 2.5 µg: 2.24%, p = 0.2; 5 µg: 2.22%, p = 0.02). There was a greater benefit with tiotropium 5 vs. 2.5 µg. No treatment-related adverse events or unexpected safety findings were observed in patients taking tiotropium.. Tiotropium significantly improved lung function in people with cystic fibrosis. The improvement was greater with the higher dose than the lower dose, with no difference in adverse events.. ClinicalTrials.gov NCT00737100 EudraCT 2008-001156-43.

Topics: Administration, Inhalation; Adolescent; Adult; Child; Cystic Fibrosis; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Respiratory Function Tests; Scopolamine Derivatives; Tiotropium Bromide; Young Adult

Chronic lung disease is the leading cause of death in patients with Cystic Fibrosis (CF) and is often treated with bronchodilators. It is not known whether long-term tiotropium bromide treatment may have a positive impact on lung function.. This retrospective cohort study estimated annual lung function decline utilizing longitudinal data for forced expiratory volume in 1 s (FEV1).. A total of 160 adult patients with CF were analyzed. The subjects treated for 24 months with tiotropium bromide had a significantly slower decline of mean annual change of FEV1 (treated: -0.3±4.0%; control: -2.3±5.0%; p = 0.0130). In patients with FEV1 ≥70% predicted, long-term tiotropium bromide treatment was associated with greater improvements in annual lung function decline (FEV1 ≥70% predicted: treated: +0.5±4.7%; control: -4.0±6.3%; p = 0.0132; FEV1 50-69% predicted: treated: -0.5±4.4%; control: -0.8±3.8%; p = 0.7142; FEV1 ≤49% predicted: treated: -0.6±3.4%; control: -2.4±4.8%; p = 0.0898).. This study suggests that long-term tiotropium bromide treatment may be associated with reduced annual decline of FEV1 in patients with CF, particularly in adults with a mild degree of severity.

Topics: Adult; Bronchodilator Agents; Cystic Fibrosis; Female; Forced Expiratory Volume; Humans; Lung; Male; Tiotropium Bromide