Chest
Volume 144, Issue 2, August 2013, Pages 490-497
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Original Research
COPD
Treadmill Endurance During 2-Year Treatment With Tiotropium in Patients With COPD: A Randomized Trial

https://doi.org/10.1378/chest.12-2613Get rights and content

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 < 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).

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 < .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.

Section snippets

Study Design

This randomized, placebo-controlled, double-blind, parallel-group study compared 96 weeks of treatment with tiotropium 18 μg via HandiHaler (Boerhringer Ingelheim International GmbH) vs placebo on exercise duration in patients with COPD.6 Patients continued all respiratory medications other than inhaled anticholinergics. An incremental treadmill protocol was conducted during screening (visit 1). During a 2-week baseline period (3 weeks for patients taking tiotropium in the 2 weeks prior to

Results

A total of 713 patients were screened, and 519 patients were randomized (placebo, n = 259; tiotropium, n = 260) (Fig 1). Altogether, 464 patients were analyzed for the primary end point. Premature discontinuation was more frequent with placebo (96 patients vs 66 patients, hazard ratio for tiotropium/placebo [95% CI], 0.61 [0.44-0.83]; P = .002) (Fig 2), with a difference in mean treatment exposure of approximately 2 months (506 ± 252 days vs 572 ± 209 days). Adverse events leading to

Discussion

Our longitudinal study of exercise ET in moderate to very severe COPD found that tiotropium resulted in consistently longer ETs than placebo at 90% of maximum work rate (approximately 40 s) over 2 years. However, the primary end point of the difference in ET between treatment groups at 96 weeks was not statistically significant. Lung function (FEV1 and FVC) was improved along with health status, as measured by the SGRQ.

Sustained bronchodilation with tiotropium reduces static and dynamic

Acknowledgments

Author contributions: Dr Cooper is the guarantor for the manuscript content.

Dr Cooper: contributed to the study design, monitoring, and the statistical analysis plan of the study; was an investigator in the trial; participated in the review and interpretation of the data; and contributed to the manuscript.

Dr Celli: contributed as an investigator in the trial, participated in the review and interpretation of the data, and contributed to the manuscript.

Dr Jardim: contributed as an investigator in

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    Funding/Support: This study was funded jointly by Boehringer Ingelheim Pharma GmbH & Co KG and Pfizer, Inc.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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