The Spirometric Efficacy of Once-Daily Dosing With Tiotropium in Stable COPD: A 13-Week Multicenter Trial

doi:10.1378/chest.118.5.1294

Chest

Volume 118, Issue 5, November 2000, Pages 1294-1302

https://doi.org/10.1378/chest.118.5.1294 Get rights and content

Study objective

To compare the bronchodilator efficacyand safety of tiotropium and placebo.

Design

A3-month, randomized, double-blind, placebo-controlled, multicentertrial.

Setting

Outpatient.

Patients

Four hundred seventy patients with stable COPD (meanFEV₁ = 38.6% predicted).

Interventions

Tiotropium 18 μg (N = 279) or placebo (N = 191) given once dailyvia a lactose-based dry-powder inhaler device.

Measurementsand results

Spirometry was evaluated on days 1, 8, 50, and 92.Data were expressed as the mean trough (ie, beforemorning dose; 23 to 24 h after previous dose) and average responseobserved in the 3 h after the dose was received. Tiotropiumproduced significant improvement in trough FEV₁ and FVC,averaging 12% greater than baseline on day 8; these improvements weremaintained on days 50 and 92. The average postdose FEV₁ was16% greater than baseline on day 1 and 20% greater than baseline onday 92; FVC was 17% greater than baseline on day 1 and 19% greaterthan baseline on day 92. Tiotropium was significantly more effectivethan placebo in both trough and average FEV₁ and FVCresponse (p < 0.001). These spirometric effects were corroborated bysignificant improvements in daily morning and evening peak expiratoryflow rate, as well as a reduction in “as-needed” albuterol use.Symptoms of wheezing and shortness of breath were significantly less inpatients receiving tiotropium, and the physician global assessmentnoted overall improvements with those treated with tiotropium relativeto placebo. The most common reported adverse event after tiotropium wasdry mouth (9.3% vs 1.6% relative to placebo; p < 0.05).

Conclusions

These data demonstrate that tiotropium is asafe and effective once-daily anticholinergic bronchodilator and shouldprove useful as first-line maintenance therapy inCOPD.

Section snippets

Design and Conduct of the Study

Twenty-five clinical centers participated in this double-blind,placebo-controlled trial with a 92-day treatment period. The study wasapproved by each center's institutional review board. All patientsprovided written informed consent.

The study group consisted of outpatients of either sex who were ≥ 40years of age and who had a clinical diagnosis of COPD as defined by theAmerican Thoracic Society (ATS).¹³ Study participants wererequired to have a smoking history of > 10 pack-years, to

Results

A total of 470 patients were randomized; 279 to tiotropium and 191to placebo. Demographic and baseline characteristics were similarbetween the two treatment groups (Table 1). The overall mean age was65.2 years, 65% of the trial population was male, and 92% were white.The mean FEV₁ at screening was 1.02 L, and themean percent predicted FEV₁ was 38.6%. The meanFEV₁/FVC ratio was 46.2%. The mean duration ofsmoking was 62.9 pack-years (range, 10.0 to 240.0 pack-years).

Of the 470 patients

Discussion

The dyspnea and diminished capacity to perform exercise andactivities of daily living associated with COPD are in large partcaused by chronic airflow limitation. Improving airflow in COPD is thebasis for bronchodilator therapy in those patients. In fact, theconcept that obstruction is irreversible in COPD can be refuted byseveral clinical trials that show improved airflow after inhaledtherapy.¹⁷¹⁸¹⁹

In addition to smoking cessation, bronchodilator therapy is thefoundation of COPD medical

US Tiotropium Study Group

Devandra Amin, MD, Palm Harbor, FL; Antonio Anzueto, MD, SanAntonio, TX; Robert Baughman, MD, Cincinnati, OH; Horst Blumberg, MD,St. Petersburg, FL; Dick D. Briggs, MD, Birmingham, AL; Jeffrey M.Cary, MD, Seattle, WA; Richard Casaburi, PhD, MD, Torrance, CA; TimothyCraig, DO, Hershey, PA; Arthur C. DeGraff, Jr., MD, Hartford, CT; JamesDonohue, MD, Chapel Hill, NC; Mitchell Friedman, MD, New Orleans, LA;Donald Auerbach, MD, Cherry Hill, NJ; Michael D. Goldman, MD, LosAngeles, CA; F. Charles

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: Supported by a grant from Boehringer Ingelheim Pharmaceuticals, Inc.(BIPI), Ridgefield, CT. Dr. Casaburi is a consultant for BIPI. Drs.Briggs and Donohue are members of the BIPI Speakers Bureau.

^†: A complete list of participants in the US Tiotropium Study Group islocated in the ^Appendix

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Chest

Clinical InvestigationsCOPDThe Spirometric Efficacy of Once-Daily Dosing With Tiotropium in Stable COPD: A 13-Week Multicenter Trial

Study objective

Design

Setting

Patients

Interventions

Measurementsand results

Conclusions

Section snippets

Design and Conduct of the Study

Results

Discussion

US Tiotropium Study Group

Life Sci

Life Sci

Chest

Chest

Chest

Optimal assessment and management of chronic obstructive pulmonary disease (COPD)

Eur Respir J

Management of chronic obstructive pulmonary disease

N Engl J Med

Ipratropium bromide

N Engl J Med

Respiratory care pharmacology and therapeutics

The role of anticholinergic bronchodilators in adult asthma and COPD

Lung

Effect of Ba 679 Br: a novel long-acting anticholinergic agent, on cholinergic neurotransmission in guinea pig and human airways

Am J Respir Crit Care Med

Tiotropium (Ba 679): pharmacology and early clinical observations

Clinical Investigations
COPD
The Spirometric Efficacy of Once-Daily Dosing With Tiotropium in Stable COPD: A 13-Week Multicenter Trial