Chest
Volume 127, Issue 3, March 2005, Pages 809-817
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Clinical Investigations: COPD
Improvement in Exercise Tolerance With the Combination of Tiotropium and Pulmonary Rehabilitation in Patients With COPD

https://doi.org/10.1378/chest.127.3.809Get rights and content

Study objectives

Pulmonary rehabilitation (PR) improves exercise tolerance in COPD patients. Tiotropium is a once-daily, inhaled anticholinergic bronchodilator that provides sustained 24-h improvements in airflow and lung hyperinflation reduction. We hypothesized that ventilatory mechanics improvements from tiotropium would permit enhanced ability to train muscles of ambulation and therefore augment exercise tolerance benefits of PR

Design

In a randomized, double-blind, placebo-controlled trial (tiotropium, n = 47; placebo, n = 44), tiotropium (18 μg qd) was administered to COPD patients participating in 8 weeks of PR (treadmill training three times a week; ≥ 30 min per session) at 17 sites. Study drug was administered 5 weeks prior to, 8 weeks during, and 12 weeks following PR. The primary end point was treadmill walking (0% incline) endurance time at 80% of maximum speed attained in an initial incremental test. The transition dyspnea index (TDI), St. George's respiratory questionnaire (SGRQ), and rescue albuterol use were secondary end points

Participants

Mean age of the 93 participants was 67 years, 57% were men, and mean FEV1 was 0.88 L (34% predicted)

Results

Mean endurance time differences (tiotropium minus placebo) prior to PR, at the end of PR, and 12 weeks after PR were 1.65 min (p = 0.183), 5.35 min (p = 0.025), and 6.60 min (p = 0.018), respectively. Mean TDI focal scores at the end of PR were 1.75 for tiotropium and 0.91 for placebo (p > 0.05). At 12 weeks after PR, TDI focal scores were 1.75 for tiotropium and 0.08 for placebo (p < 0.05). Relative to placebo, tiotropium improved SGRQ total scores by 3.86 at the end of PR and 4.44 at 12 weeks after PR (p > 0.05). Mean albuterol use declined following PR plus tiotropium, compared to PR alone (p ≤ 0.05 for 17 of 25 weeks)

Conclusions

Tiotropium in combination with PR improved endurance of a constant work rate treadmill task and produced clinically meaningful improvements in dyspnea and health status compared to PR alone. Improvements with tiotropium were sustained for 3 months following PR completion

Section snippets

Study Design

This study is a 25-week, multicenter, single-country, randomized, double-blind, parallel-group clinical trial to determine the efficacy of tiotropium inhalation capsules compared to placebo on exercise tolerance in patients with COPD participating in a PR program. Randomization to tiotropium, 18 μg qd, or placebo occurred in a 1:1 ratio. Tiotropium or matching placebo were supplied as a dry-powder capsule and inhaled (HandiHaler device; Boehringer Ingelheim; Ingelheim, Germany) in the morning.

Results

A total of 108 patients were randomized and received at least one dose of study medication. The full analysis data sets included all randomized patients who had adequate baseline measurements and at least one efficacy measurement after the multiple administration of study medication. By this definition, 12 patients (6 in each treatment group) were excluded from all efficacy analyses. In addition to the 12 patients excluded from all efficacy analyses, 5 additional patients were excluded from the

Discussion

The purpose of the present study was to determine whether tiotropium enhances exercise training benefits in PR programs in COPD patients. In addition, this study sought to assess the impact of tiotropium on dyspnea and health-related quality of life following PR. Finally, the inclusion of a 12-week postrehabilitation period was used to determine whether benefits of PR are better maintained with tiotropium. Patients receiving tiotropium showed significantly longer exercise endurance time at the

References (25)

  • W Vincken et al.

    Improvement in health status in patients with COPD during one year treatment with tiotropium

    Eur Respir J

    (2002)
  • DE O'Donnell et al.

    Effects of tiotropium on lung hyperinflation, dyspnea and exercise tolerance in COPD

    Eur Respir J

    (2004)
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    Dr. Casaburi holds the Alvin Grancell/Mary Burns Chair in the Rehabilitative Sciences. Dr. Casaburi is a consultant of Boehringer-Ingelheim Pharmaceuticals and Pfizer and serves on their Academic Advisory Board. Dr. Cooper receives research support from Boehringer-Ingelheim Pharmaceuticals and is a member of their Speaker's Bureau and Scientific Advisory Board. Drs. Witek and Kesten areemployees of Boehringer-Ingelheim Pharmaceuticals. This study was supported by Boehringer-Ingelheim Pharmaceuticals Inc. and Pfizer Inc

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