title: Treadmill endurance during 2-year treatment with tiotropium in patients with COPD: a randomized trial.
abstract: BACKGROUND
  Disease progression in COPD is associated with a decline in exercise performance over time. We assessed whether tiotropium might mitigate this by determining its effect on treadmill endurance time (ET) over 2 years.
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled trial of tiotropium, 18 μg daily, in patients with COPD (FEV1/FVC &lt; 70%; postbronchodilator FEV1 &lt; 65%). The primary end point was ET at 90% of baseline maximum work rate at 96 weeks. Secondary end points were ET at other visits, ET by smoking status, spirometry, and St. George's Respiratory Questionnaire (SGRQ).
  
  
  RESULTS
  A total of 519 patients were randomized (tiotropium 260, placebo 259). Mean age was 65 years, 77% were men, 34% were continuing smokers, and mean FEV1 was 1.25 L (44% predicted). Significantly more patients discontinued placebo (hazard ratio [95% CI], 0.61 [0.44-0.83]). Baseline ET was 301 s (improvement tiotropium/placebo was 13% overall; P = .009; 18% at 48 weeks, P = .004; 13% at 96 weeks, P = .106). In patients with baseline ET between 2 and 10 min (n = 404), improvement at 96 weeks was 19% (P = .04). Current smokers had higher ET with tiotropium vs placebo (P = .018). FEV1/FVC improved with tiotropium (P &lt; .01). SGRQ total score at 96 weeks improved with tiotropium vs placebo by 4.03 units (P = .007).
  
  
  CONCLUSIONS
  Treadmill ET was numerically greater over 2 years with tiotropium vs placebo. However, the 96-week difference was not statistically significant. Spirometry and health status also improved with tiotropium over 2 years, attesting to the benefits of long-acting bronchodilator therapy.
  
  
  BACKGROUND
  ClinicalTrials.gov; No.: NCT00525512; URL: www.clinicaltrials.gov.
authors.affiliation: David Geffen School of Medicine, University of California, Los Angeles, CA. Electronic address: ccooper@mednet.ucla.edu.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Cooper
authors.affiliation: Brigham and Women's Hospital, Boston, MA.
authors.forename: Bartolome R
authors.initials: BR
authors.lastname: Celli
authors.affiliation: Federal University of São Paulo, São Paulo, Brazil.
authors.forename: José R
authors.initials: JR
authors.lastname: Jardim
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Baltimore, MD.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wise
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT.
authors.forename: Daniel
authors.initials: D
authors.lastname: Legg
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT.
authors.forename: Junhai
authors.initials: J
authors.lastname: Guo
authors.affiliation: Cytori Therapeutics, Inc, San Diego, CA.
authors.forename: Steven
authors.initials: S
authors.lastname: Kesten
mesh_terms: D000368:Aged; D001993:Bronchodilator Agents / Q000494:pharmacology*; D018450:Disease Progression; D004311:Double-Blind Method; D023381:Endpoint Determination; D005080:Exercise Test; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D008297:Male; D008875:Middle Aged; D010807:Physical Endurance / Q000502:physiology*; D010919:Placebos; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology*; D012129:Respiratory Function Tests; D012602:Scopolamine Derivatives / Q000494:pharmacology*; D012907:Smoking / Q000009:adverse effects; D000069447:Tiotropium Bromide
chemical_list: D001993:Bronchodilator Agents; D010919:Placebos; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide