Chest
Volume 122, Issue 1, July 2002, Pages 47-55
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Clinical Investigations
Copd
A 6-Month, Placebo-Controlled Study Comparing Lung Function and Health Status Changes in COPD Patients Treated With Tiotropium or Salmeterol

https://doi.org/10.1378/chest.122.1.47Get rights and content

Background

Tiotropium, a once-daily anticholinergic, and salmeterol represent two inhaled, long-acting bronchodilators from different pharmacologic classes. A trial was designed to examine the efficacy and safety of both compounds with multiple outcome measures, including lung function, dyspnea, and health-related quality of life (HRQoL) in patients with COPD.

Methods

A 6-month, randomized, placebo-controlled, double-blind, double-dummy, parallel-group study of tiotropium, 18 μg once daily via dry-powder inhaler, compared with salmeterol, 50 μg bid via metered-dose inhaler, was conducted in patients with COPD. Efficacy was assessed by 12-h monitoring of spirometry, transition dyspnea index (TDI), and the St. George's Respiratory Questionnaire (SGRQ).

Results

A total of 623 patients participated (tiotropium, n= 209; salmeterol, n = 213; and placebo, n = 201). The groups were similar in age (mean, 65 years), gender (75% men), and baseline FEV1 (mean, 1.08 ± 0.37 L; percent predicted, 40 ± 12% [± SD]). Compared with placebo treatment, the mean predose morning FEV1 following 6 months of therapy increased significantly more for the tiotropium group (0.14 L) than the salmeterol group (0.09 L; p < 0.01). The average FEV1 (0 to 12 h) for tiotropium was statistically superior to salmeterol (difference, 0.08 L; p < 0.001). Tiotropium improved TDI focal score by 1.02 U compared with placebo (p = 0.01), whereas there was no significant change in TDI focal score with salmeterol (0.24 U). Tiotropium was superior to salmeterol in improving TDI focal score (p < 0.05). At 6 months, the mean improvement in SGRQ total score vs baseline was tiotropium, − 5.14 U (p < 0.05 vs placebo); salmeterol, − 3.54 U (p = 0.4 vs placebo); and placebo, − 2.43 U. A statistically higher proportion of patients receiving tiotropium achieved at least a 4-U change in SGRQ score compared to patients receiving placebo. Both active drugs reduced the need for rescue albuterol (p < 0.0001).

Conclusions

Tiotropium once daily produces superior bronchodilation, improvements in dyspnea, and proportion of patients achieving meaningful changes in HRQoL compared to twice-daily salmeterol in patients with COPD.

Section snippets

Study Design

This was a 6-month, placebo-controlled, multicenter, multinational, randomized, parallel-group study to compare the long-term efficacy of tiotropium dry-powder inhalation capsules with salmeterol inhalation aerosol in patients with COPD. The drugs were administered in a double-dummy design with tiotropium, 18 μg, or placebo capsules received once daily in the morning, and salmeterol, 50 μg, or placebo metered-dose inhaler (MDI) received twice daily (every 12 h). Capsules were administered using

Results

A total of 623 patients were entered into the trial, with 209 patients receiving tiotropium, 213 receiving salmeterol, and 201 receiving placebo. A greater proportion of patients in the tiotropium group (88%) completed the 6-month treatment period compared with the salmeterol group (83%) and the placebo group (72%). The majority of premature discontinuations were secondary to adverse events, the most frequent of which were related to underlying respiratory disease. A significantly greater

Discussion

Bronchodilators are the mainstay of pharmacotherapy for patients with COPD.123 Mechanism of action, route of administration, frequency of administration, onset of action, duration of action, symptomatic improvement, and side effect profile differentiates various bronchodilator medications. Generally, inhaled therapy has been preferred over oral therapy due to the targeted delivery to the lung, superior spirometric results, and superior tolerability. In addition, differential benefits have led

Appendix

The following investigators participated in this study: Professor D. McKenzie, Dr. E. Beck, Dr. M.V. Middle, Professor D. Ruffin, Dr. T. Schaberg, Dr. J. M. Montserrat, Professor P. Thompson, Dr. C.F. Marchioni, Dr. M. Miravitlles, Professor J. Aumann, Dr. C. Sanguinetti, Dr. J. Morera, Professor W. Vincken, Professor V. Brusasco, Dr. S.J. Langley, Dr. J. Verhaert, Dr. J.A. van Noord, Dr. R.J. White, Dr. N. Zamel, Dr. T.A. Bantje, Dr. A.J. Winning, Dr. R. Hodder, Dr. A.P.M. Greefhorst, Dr. K.R.

ACKNOWLEDGMENT

We are grateful to the patients and their families, and the coordinators, nurses, and therapists for their dedication to the study.

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    Drs. Donohue, van Noord, Bateman, and Langley have been consultants for Boehringer Ingelheim.

    Supported by Boehringer Ingelheim Pharmaceuticals, Inc.

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