title: The Tiotropium Safety and Performance in Respimat Trial (TIOSPIR), a large scale, randomized, controlled, parallel-group trial-design and rationale.
abstract: BACKGROUND
  Tiotropium bromide is an effective therapy for COPD patients. Comparing across programs tiotropium Respimat Soft Mist inhaler was at least as efficacious as tiotropium HandiHaler, however, concerns have been raised about tiotropium's safety when given via Respimat.
  
  
  METHODS
  The TIOSPIR trial (NCT01126437) compares the safety and efficacy of tiotropium Respimat 5 μg once daily (marketed) and 2.5 μg once daily (investigational) with tiotropium HandiHaler 18 μ once daily (marketed). The hypotheses to be tested are 1). that tiotropium Respimat 5 μg once daily and Respimat 2.5 μg once daily are non-inferior to HandiHaler in terms of all-cause mortality, and 2). that tiotropium Respimat 5 μg once daily is superior to HandiHaler 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.
  
  
  CONCLUSIONS
  TIOSPIR will provide precise estimates of the relative safety and efficacy of the Respimat and HandiHaler formulations of tiotropium, assess potential dose-dependence of important outcomes and provide information on the clinical epidemiology of COPD in a large international patient cohort.
authors.affiliation: Johns Hopkins Asthma & Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. rwise@jhmi.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wise
authors.forename: Antonio
authors.initials: A
authors.lastname: Anzueto
authors.forename: Peter
authors.initials: P
authors.lastname: Calverley
authors.forename: Ronald
authors.initials: R
authors.lastname: Dahl
authors.forename: Daniel
authors.initials: D
authors.lastname: Dusser
authors.forename: Gordon
authors.initials: G
authors.lastname: Pledger
authors.forename: Michael
authors.initials: M
authors.lastname: Koenen-Bergmann
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Joseph
authors.forename: Daniel
authors.initials: D
authors.lastname: Cotton
authors.forename: Bernd
authors.initials: B
authors.lastname: Disse
mesh_terms: D000280:Administration, Inhalation; D001993:Bronchodilator Agents / Q000008:administration & dosage; D005260:Female; D006801:Humans; D038622:Internationality; D008297:Male; D036501:Metered Dose Inhalers / Q000706:statistics & numerical data*; D015995:Prevalence; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000453:epidemiology*; D012307:Risk Factors; D012602:Scopolamine Derivatives / Q000008:administration & dosage*; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide
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