title: The Tiotropium Safety and Performance in Respimat® (TIOSPIR®) Trial: Spirometry Outcomes.
abstract: BACKGROUND
  Tiotropium Safety and Performance in Respimat® (TIOSPIR®) compared the safety and efficacy of tiotropium Respimat® and tiotropium HandiHaler® in patients with chronic obstructive pulmonary disease (COPD). A prespecified spirometry substudy compared the lung function efficacy between treatment groups.
  
  
  METHODS
  TIOSPIR® was a large-scale, long-term (2.3-year), event-driven, randomized, double-blind, parallel-group trial of 17,135 patients with COPD. In the spirometry substudy, trough forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured at baseline and every 24 weeks for the duration of the trial.
  
  
  RESULTS
  The substudy included 1370 patients who received once-daily tiotropium Respimat® 5 μg (n = 461), 2.5 μg (n = 464), or tiotropium HandiHaler® 18 μg (n = 445). Adjusted mean trough FEV1 (average 24-120 weeks) was 1.285, 1.258, and 1.295 L in the Respimat® 5 μg, 2.5 μg, and HandiHaler® 18 μg groups (difference versus HandiHaler® [95 % CI]: -10 [-38, 18] mL for Respimat® 5 μg and, -37 [-65, -9] mL for Respimat® 2.5 μg); achieving noninferiority to tiotropium HandiHaler® 18 μg for tiotropium Respimat® 5 but not for 2.5 μg (prespecified analysis). Adjusted mean trough FVC was 2.590, 2.544, and 2.593 L in the Respimat® 5 μg, 2.5 μg, and HandiHaler® 18 μg groups. The rates of FEV1 decline over 24 to 120 weeks were similar for the three treatment arms (26, 40, and 34 mL/year for the tiotropium Respimat® 5-μg, 2.5-μg, and HandiHaler® 18-μg groups). The rate of FEV1 decline in GOLD I + II patients was greater than in GOLD III + IV patients (46 vs. 23 mL/year); as well as in current versus ex-smokers, in patients receiving combination therapies at baseline versus not, and in those experiencing an exacerbation during the study versus not.
  
  
  CONCLUSIONS
  The TIOSPIR® spirometry substudy showed that tiotropium Respimat® 5 μg was noninferior to tiotropium HandiHaler® 18 μg for trough FEV1, but Respimat® 2.5 μg was not. Tiotropium Respimat® 5 μg provides similar bronchodilator efficacy to tiotropium HandiHaler® 18 μg with comparable rates of FEV1 decline. The rate of FEV1 decline varied based on disease severity, with a steeper rate of decline observed in patients with moderate airway obstruction.
  
  
  BACKGROUND
  NCT01126437.
authors.affiliation: Pulmonary/Critical Care, University of Texas Health Science Center, and South Texas Veterans Health Care System, 111E, 7400 Merton Minter Blvd, San Antonio, TX, 78229, USA. anzueto@uthscsa.edu.
authors.forename: Antonio
authors.initials: A
authors.lastname: Anzueto
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA. rwise@jhmi.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Wise
authors.affiliation: Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK. pmacal@liverpool.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Calverley
authors.affiliation: Service de Pneumologie Hôpital Cochin, Paris, France. daniel.dusser@cch.aphp.fr.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dusser
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA. wenbo.tang@boehringer-ingelheim.com.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Tang
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany. norbert.metzdorf@boehringer-ingelheim.com.
authors.forename: Norbert
authors.initials: N
authors.lastname: Metzdorf
authors.affiliation: Odense University Hospital, Odense, Denmark. ronald.dahl2@rsyd.dk.
authors.forename: Ronald
authors.initials: R
authors.lastname: Dahl
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D013147:Spirometry; D013997:Time Factors; D000069447:Tiotropium Bromide / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D001993:Bronchodilator Agents; D000069447:Tiotropium Bromide