BACKGROUND: Static and dynamic lung hyperinflation are associated with exercise impairment and poor outcomes in COPD patients. Aclidinium bromide is a novel, long-acting inhaled muscarinic antagonist currently in development for COPD treatment. METHODS:Patients with moderate to severe COPD (N = 181) were randomized to once-daily aclidinium 200 μg or placebo for 6 weeks. Constant work rate cycling exercises at 75% of peak work rate were performed at baseline, Day 1, Week 3, and Week 6. The primary efficacy measure was change in exercise endurance time (ET) from baseline to Week 6. Secondary outcomes included changes in trough forced expiratory volume in 1 s (FEV(1)), inspiratory capacity (IC), IC/total lung capacity (TLC), and functional residual capacity (FRC) from baseline to Day 1, Week 3, and Week 6. Borg dyspnea scores during exercise, locus of symptom limitation, and safety measures were assessed. RESULTS: Aclidinium significantly improved ET on Day 1 (P = 0.0002), and improvements were sustained through Week 3 (P = 0.0007) and Week 6 (P = 0.0042) vs placebo. Compared with placebo, aclidinium improved trough FEV(1), IC, and IC/TLC at Weeks 3 and 6 (P < 0.05 for all). Exertional dyspnea scores at isotime were reduced on Day 1, Week 3, and Week 6 for aclidinium vs placebo (P < 0.05). Furthermore, the likelihood of stopping exercise due to breathing discomfort was lower in the aclidinium group at study end (P = 0.0208) compared with placebo. No differences in safety outcomes were reported between treatments. CONCLUSIONS: Aclidinium significantly increased exercise tolerance, improved airflow obstruction and lung hyperinflation, and was safe and well tolerated. REGISTRATION OF TRIAL: This trial was registered with ClinicalTrials.gov (NCT00500318) under the name "A Study of Exercise Endurance and Lung Hyperinflation in Patients with Moderate to Severe COPD".
RCT Entities:
BACKGROUND: Static and dynamic lung hyperinflation are associated with exercise impairment and poor outcomes in COPDpatients. Aclidinium bromide is a novel, long-acting inhaled muscarinic antagonist currently in development for COPD treatment. METHODS:Patients with moderate to severe COPD (N = 181) were randomized to once-daily aclidinium 200 μg or placebo for 6 weeks. Constant work rate cycling exercises at 75% of peak work rate were performed at baseline, Day 1, Week 3, and Week 6. The primary efficacy measure was change in exercise endurance time (ET) from baseline to Week 6. Secondary outcomes included changes in trough forced expiratory volume in 1 s (FEV(1)), inspiratory capacity (IC), IC/total lung capacity (TLC), and functional residual capacity (FRC) from baseline to Day 1, Week 3, and Week 6. Borg dyspnea scores during exercise, locus of symptom limitation, and safety measures were assessed. RESULTS:Aclidinium significantly improved ET on Day 1 (P = 0.0002), and improvements were sustained through Week 3 (P = 0.0007) and Week 6 (P = 0.0042) vs placebo. Compared with placebo, aclidinium improved trough FEV(1), IC, and IC/TLC at Weeks 3 and 6 (P < 0.05 for all). Exertional dyspnea scores at isotime were reduced on Day 1, Week 3, and Week 6 for aclidinium vs placebo (P < 0.05). Furthermore, the likelihood of stopping exercise due to breathing discomfort was lower in the aclidinium group at study end (P = 0.0208) compared with placebo. No differences in safety outcomes were reported between treatments. CONCLUSIONS:Aclidinium significantly increased exercise tolerance, improved airflow obstruction and lung hyperinflation, and was safe and well tolerated. REGISTRATION OF TRIAL: This trial was registered with ClinicalTrials.gov (NCT00500318) under the name "A Study of Exercise Endurance and Lung Hyperinflation in Patients with Moderate to Severe COPD".
Authors: Gerard J Criner; Jean Bourbeau; Rebecca L Diekemper; Daniel R Ouellette; Donna Goodridge; Paul Hernandez; Kristen Curren; Meyer S Balter; Mohit Bhutani; Pat G Camp; Bartolome R Celli; Gail Dechman; Mark T Dransfield; Stanley B Fiel; Marilyn G Foreman; Nicola A Hanania; Belinda K Ireland; Nathaniel Marchetti; Darcy D Marciniuk; Richard A Mularski; Joseph Ornelas; Jeremy D Road; Michael K Stickland Journal: Chest Date: 2015-04 Impact factor: 9.410
Authors: Gerard J Criner; Jean Bourbeau; Rebecca L Diekemper; Daniel R Ouellette; Donna Goodridge; Paul Hernandez; Kristen Curren; Meyer S Balter; Mohit Bhutani; Pat G Camp; Bartolome R Celli; Gail Dechman; Mark T Dransfield; Stanley B Fiel; Marilyn G Foreman; Nicola A Hanania; Belinda K Ireland; Nathaniel Marchetti; Darcy D Marciniuk; Richard A Mularski; Joseph Ornelas; Jeremy D Road; Michael K Stickland Journal: Chest Date: 2015-04 Impact factor: 9.410