Treadmill Endurance During 2-Year Treatment With Tiotropium in Patients With COPD : A Randomized Trial

BackgroundDisease 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.MethodsThis was a randomized, double-blind, placebo-controlled trial of tiotropium, 18 μg daily, in patients with COPD (FEV1/FVC < 70%; postbronchodilator FEV1 < 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).ResultsA 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 < .01). SGRQ total score at 96 weeks improved with tiotropium vs placebo by 4.03 units (P = .007).ConclusionsTreadmill 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.Trial registryClinicalTrials.gov; No.: NCT00525512; URL: www.clinicaltrials.gov