randomized, controlled, parallel-group trial-design and rationale

Background: Tiotropium bromide is an effective therapy for COPD patients. Comparing across programs tiotropium Respimat W Soft Mist ™ inhaler was at least as efficacious as tiotropium HandiHaler W , however, concerns have been raised about tiotropium’s safety when given via Respimat W . Methods: The TIOSPIR W trial (NCT01126437) compares the safety and efficacy of tiotropium Respimat W 5 μg once daily (marketed) and 2.5 μg once daily (investigational) with tiotropium HandiHaler W 18 μ once daily (marketed). The hypotheses to be tested are 1). that tiotropium Respimat W 5 μg once daily and Respimat W 2.5 μg once daily are non-inferior to HandiHaler W in terms of all-cause mortality, and 2). that tiotropium Respimat W 5 μg once daily is superior to HandiHaler W in terms of time to first exacerbation. A spirometry substudy evaluates the bronchodilator efficacy. The trial is a randomized, double-blind, double dummy, event-driven, parallel group study. Participants can use any background treatment for COPD except inhaled anticholinergic agents. The study encompasses a wide range of COPD patients, e.g. patients with stable cardiac diseases including arrhythmia can be included. Clinical sites are international and include both primary care as well as specialists. Results: To date, over 17,000 participants have been randomized from over 1200 sites in 50 countries with an anticipated treatment duration of 2–3 years. Conclusion: TIOSPIR W will provide precise estimates of the relative safety and efficacy of the Respimat W and HandiHaler W formulations of tiotropium, assess potential dose-dependence of important outcomes and provide