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Clinical Trial
. 2014 Sep 4;9(9):e106195.
doi: 10.1371/journal.pone.0106195. eCollection 2014.

Testing two different doses of tiotropium Respimat® in cystic fibrosis: phase 2 randomized trial results

Judy M Bradley  1 , Paul Koker  2 , Qiqi Deng  2 , Petra Moroni-Zentgraf  3 , Felix Ratjen  4 , David E Geller  5 , J Stuart Elborn  6 ; Tiotropium Cystic Fibrosis Study Group
Collaborators, Affiliations
Clinical Trial

Testing two different doses of tiotropium Respimat® in cystic fibrosis: phase 2 randomized trial results

Judy M Bradley et al. PLoS One. .

Abstract

Background: 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.

Methods: 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.

Findings: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT00737100 EudraCT 2008-001156-43.

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Conflict of interest statement

Competing Interests: The authors have read the journal’s policy, declare the following conflicts of interest, and confirm that these do not alter their adherence to PLOS ONE policies on sharing data and materials: JSE acted as a consultant for Boehringer Ingelheim and was principal investigator for this study; JMB declares no conflicts; PK, QD, and PMZ are employees of Boehringer Ingelheim; FR acts as a consultant for Boehringer Ingelheim and is the principal investigator for the phase 3 study of tiotropium in CF; DEG declares no conflicts related to bronchodilators in CF.

Figures

Figure 1
Figure 1. Flow diagram of participant recruitment and randomization .
Figure 2
Figure 2. Adjusted mean FEV1 AUC0–4h (percent-predicted ± SE) change from baseline (full analysis set).
AUC0–4h, area under the curve from 0 to 4 hours; FEV1, forced expiratory volume in 1 second.
See this image and copyright information in PMC

References

    1. Davis PB, Drumm M, Konstan MW (1996) Cystic fibrosis. Am J Respir Crit Care Med 154: 1229–1256. - PubMed
    1. Konstan MW, Butler SM, Schidlow DV, Morgan WJ, Julius JR, et al. (1999) Patterns of medical practice in cystic fibrosis: part II. Use of therapies. Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis. Pediatr Pulmonol 28: 248–254. - PubMed
    1. Johnson C, Butler SM, Konstan MW, Morgan W, Wohl ME (2003) Factors influencing outcomes in cystic fibrosis: a center-based analysis. Chest 123: 20–27. - PubMed
    1. Colombo JL (2003) Long-acting bronchodilators in cystic fibrosis. Curr Opin Pulm Med 9: 504–508. - PubMed
    1. Cropp GJ (1996) Effectiveness of bronchodilators in cystic fibrosis. Am J Med 100: 19S–29S. - PubMed

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