ANNALSATS Articles in Press. Published on 07-October-2014 as 10.1513/AnnalsATS.201404-174OC
Page 1 of 65
Effects of Tiotropium on Hyperinflation and Treadmill Exercise Tolerance in Mild– Moderate Chronic Obstructive Pulmonary Disease
Richard Casaburi1, François Maltais2, Janos Porszasz1, Frank Albers3,*, Qiqi Deng3, Ahmar Iqbal4,*, Heather A. Paden3, Denis E. O’Donnell5, and on behalf of the 205.440 investigators
1
Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor-
UCLA Medical Center, Torrance, California; 2Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada; 3Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut; 4Pfizer Inc, New York, New York; 5Queen’s University & Kingston General Hospital, Kingston, Ontario, Canada *At the time of the study
Correspondence: Richard Casaburi, PhD, MD Rehabilitation Clinical Trials Center Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center Torrance, CA 90502. Phone: +1 310 222 8200 E-mail: [email protected]
Author Contributions: R.C. was the study co-ordinating investigator, contributed to study design, acquired and interpreted data, and was responsible for manuscript concept, drafting, and revisions. F.M. and D.E.O. acquired and interpreted data, and contributed to and reviewed drafts of the manuscript. J.P. participated in study design, acquired and interpreted data, and contributed to and reviewed drafts of the manuscript. F.A. contributed to preparation and design of the study, interpreted data, and contributed to and reviewed drafts of the manuscript. Q.D. contributed to data analysis, and contributed to and reviewed drafts
1
Copyright © 2014 by the American Thoracic Society
ANNALSATS Articles in Press. Published on 07-October-2014 as 10.1513/AnnalsATS.201404-174OC
of the manuscript. A.I. interpreted data, and contributed to and reviewed drafts of the manuscript. H.A.P. as study clinical monitor, participated in study design, interpreted data, and contributed to and reviewed drafts of the manuscript. All authors approved the final manuscript.
This work was supported by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) and Pfizer, Inc. and writing and editorial support by Envision Scientific Solutions was contracted and compensated by BIPI and Pfizer, Inc.
Running title: Tiotropium and Exercise in Mild–Moderate COPD
Descriptor number: 9.14 COPD: Pharmacological Treatment
Keywords: chronic obstructive pulmonary disease; GOLD; inspiratory capacity; dyspnea; dynamic hyperinflation
Body Count = 3936
This article has a data supplement, which is accessible from this issue's table of content online at www.atsjournals.org
2
Copyright © 2014 by the American Thoracic Society
Page 2 of 65
ANNALSATS Articles in Press. Published on 07-October-2014 as 10.1513/AnnalsATS.201404-174OC
Page 3 of 65
1
ABSTRACT
2
Rationale: Bronchodilator therapy represents a potentially valuable therapeutic option to
3
increase exercise tolerance and enhance lung function in mild-to-moderate chronic
4
obstructive pulmonary disease (COPD).
5
Objectives: To determine effects of tiotropium on pulmonary hyperinflation and exercise
6
tolerance in symptomatic Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1
7
and 2 COPD patients who experienced inspiratory capacity decrease ≥100 mL during
8
incremental and constant work rate treadmill exercise.
9
Methods: 22-week, randomized, double-blind, two-period cross-over study evaluated efficacy
10
of once-daily tiotropium bromide (18 µg) versus placebo in GOLD 1 and 2 COPD patients.
11
Primary endpoint was between-group (tiotropium vs. placebo) difference in inspiratory
12
capacity at isotime (i.e. at the time the shortest test ended) during constant work rate treadmill
13
exercise from baseline to the end of a 6-week treatment period. Key secondary endpoints
14
included differences in exercise duration and exertional dyspnea. Safety was assessed by
15
recording adverse events.
16
Measurements and Main Results: Study population comprised 48 GOLD 1 and 78 GOLD 2
17
patients. Resting inspiratory capacity significantly improved with tiotropium versus placebo
18
in the overall (P
Page 1 of 65
Effects of Tiotropium on Hyperinflation and Treadmill Exercise Tolerance in Mild– Moderate Chronic Obstructive Pulmonary Disease
Richard Casaburi1, François Maltais2, Janos Porszasz1, Frank Albers3,*, Qiqi Deng3, Ahmar Iqbal4,*, Heather A. Paden3, Denis E. O’Donnell5, and on behalf of the 205.440 investigators
1
Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor-
UCLA Medical Center, Torrance, California; 2Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada; 3Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut; 4Pfizer Inc, New York, New York; 5Queen’s University & Kingston General Hospital, Kingston, Ontario, Canada *At the time of the study
Correspondence: Richard Casaburi, PhD, MD Rehabilitation Clinical Trials Center Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center Torrance, CA 90502. Phone: +1 310 222 8200 E-mail: [email protected]
Author Contributions: R.C. was the study co-ordinating investigator, contributed to study design, acquired and interpreted data, and was responsible for manuscript concept, drafting, and revisions. F.M. and D.E.O. acquired and interpreted data, and contributed to and reviewed drafts of the manuscript. J.P. participated in study design, acquired and interpreted data, and contributed to and reviewed drafts of the manuscript. F.A. contributed to preparation and design of the study, interpreted data, and contributed to and reviewed drafts of the manuscript. Q.D. contributed to data analysis, and contributed to and reviewed drafts
1
Copyright © 2014 by the American Thoracic Society
ANNALSATS Articles in Press. Published on 07-October-2014 as 10.1513/AnnalsATS.201404-174OC
of the manuscript. A.I. interpreted data, and contributed to and reviewed drafts of the manuscript. H.A.P. as study clinical monitor, participated in study design, interpreted data, and contributed to and reviewed drafts of the manuscript. All authors approved the final manuscript.
This work was supported by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) and Pfizer, Inc. and writing and editorial support by Envision Scientific Solutions was contracted and compensated by BIPI and Pfizer, Inc.
Running title: Tiotropium and Exercise in Mild–Moderate COPD
Descriptor number: 9.14 COPD: Pharmacological Treatment
Keywords: chronic obstructive pulmonary disease; GOLD; inspiratory capacity; dyspnea; dynamic hyperinflation
Body Count = 3936
This article has a data supplement, which is accessible from this issue's table of content online at www.atsjournals.org
2
Copyright © 2014 by the American Thoracic Society
Page 2 of 65
ANNALSATS Articles in Press. Published on 07-October-2014 as 10.1513/AnnalsATS.201404-174OC
Page 3 of 65
1
ABSTRACT
2
Rationale: Bronchodilator therapy represents a potentially valuable therapeutic option to
3
increase exercise tolerance and enhance lung function in mild-to-moderate chronic
4
obstructive pulmonary disease (COPD).
5
Objectives: To determine effects of tiotropium on pulmonary hyperinflation and exercise
6
tolerance in symptomatic Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1
7
and 2 COPD patients who experienced inspiratory capacity decrease ≥100 mL during
8
incremental and constant work rate treadmill exercise.
9
Methods: 22-week, randomized, double-blind, two-period cross-over study evaluated efficacy
10
of once-daily tiotropium bromide (18 µg) versus placebo in GOLD 1 and 2 COPD patients.
11
Primary endpoint was between-group (tiotropium vs. placebo) difference in inspiratory
12
capacity at isotime (i.e. at the time the shortest test ended) during constant work rate treadmill
13
exercise from baseline to the end of a 6-week treatment period. Key secondary endpoints
14
included differences in exercise duration and exertional dyspnea. Safety was assessed by
15
recording adverse events.
16
Measurements and Main Results: Study population comprised 48 GOLD 1 and 78 GOLD 2
17
patients. Resting inspiratory capacity significantly improved with tiotropium versus placebo
18
in the overall (P
