Tiotropium Respimat in cystic fibrosis: Phase 3 and Pooled phase 2/3 randomized trials

J Cyst Fibros. 2015 Sep;14(5):608-14. doi: 10.1016/j.jcf.2015.03.004. Epub 2015 Mar 26.


Background: 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.

Methods: 12-week, randomized, double-blind, placebo-controlled trial of tiotropium Respimat 5 μg once daily in patients with CF (N=463).

Results: 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).

Conclusion: Tiotropium was well tolerated in patients with CF; lung function improvements compared with placebo were not statistically significant in the phase 3 trial.

Clinical trials: 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.

Keywords: Bronchodilator; Cystic fibrosis; Respimat; Tiotropium.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Cholinergic Antagonists / administration & dosage
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / physiopathology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Forced Expiratory Flow Rates / physiology
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Tiotropium Bromide / administration & dosage*
  • Treatment Outcome
  • Young Adult


  • Cholinergic Antagonists
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT00737100
  • ClinicalTrials.gov/NCT01179347
  • EudraCT/2008-001156-43
  • EudraCT/2010-019802-17