Thierry Troosters1,2, François Maltais3, Nancy Leidy4, Kim L Lavoie5,6, Maria Sedeno7, Wim Janssens8,9, Judith Garcia-Aymerich10, Damijan Erzen11, Dorothy De Sousa12, Lawrence Korducki13, Alan Hamilton12, Jean Bourbeau7. 1. 1 Department of Rehabilitation Sciences, and. 2. 2 Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium. 3. 3 Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Québec, Canada. 4. 4 Evidera, Bethesda, Maryland. 5. 5 Montréal Behavioural Medicine Centre, Research Centre, Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-de-l'Ile-de Montréal Hôpital du Sacré-Coeur de Montreal, Montréal, Québec, Canada. 6. 6 Department of Psychology, University of Québec at Montréal, Montréal, Québec, Canada. 7. 7 Research Institute of the McGill University Health Centre and McGill University, Montréal, Québec, Canada. 8. 9 Department of Chronic Diseases, Metabolism and Ageing, Laboratory of Respiratory Diseases, Katholieke Universiteit Leuven, Leuven, Belgium. 9. 8 University Hospital Gasthuisberg, Respiratory Division, Leuven, Belgium. 10. 10 Instituto de Salud Global Barcelona, Centre for Research in Environmental Epidemiology, Universitat Pompeu Fabra, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Barcelona, Spain. 11. 11 Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany. 12. 12 Boehringer Ingelheim (Canada) Ltd., Burlington, Ontario, Canada; and. 13. 13 Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut.
Abstract
RATIONALE: Bronchodilation and exercise training (ExT) improve exercise tolerance in patients with chronic obstructive pulmonary disease (COPD); however, behavior modification is required to impact daily physical activity (PA). OBJECTIVES: To assess whether tiotropium/olodaterol, with or without ExT, would improve exercise endurance time (EET) and PA compared with placebo in patients participating in a self-management behavior-modification (SMBM) program. METHODS: This was a 12-week, randomized, partially double-blind, placebo-controlled, parallel-group trial in patients with COPD (PHYSACTO; NCT02085161). All patients were enrolled into SMBM and randomized 1:1:1:1 to once-daily placebo, tiotropium 5 μg, tiotropium/olodaterol 5/5 μg, or tiotropium/olodaterol 5/5 μg plus 8 weeks ExT. EET, measured by endurance shuttle walk test after 8 weeks, was the primary endpoint. Additional endpoints assessed downstream effects on PA (measured via accelerometry), and activity-related dyspnea and difficulty (using validated patient-reported questionnaires). MEASUREMENTS AND MAIN RESULTS:SMBM plus tiotropium/olodaterol, with or without ExT, significantly improved EET at Week 8 versus SMBM plus placebo (treatment ratio vs. placebo: with ExT, 1.46; 95% confidence interval, 1.20-1.78; P = 0.0002; without ExT, 1.29; 95% confidence interval, 1.06-1.57; P = 0.0109). No significant increases in steps per day from baseline were observed over SMBM plus placebo at Week 12 (increase of 1,098) when other therapies were added. Adding tiotropium/olodaterol, with or without ExT, to SMBM reduced activity-related dyspnea versus placebo, whereas adding tiotropium/olodaterol plus ExT reduced activity-related difficulty. CONCLUSIONS:Tiotropium/olodaterol, with or without ExT, improved EET in patients with COPD taking part in an SMBM program. Combination bronchodilation, with or without ExT, did not provide additional increases in objective PA compared with SMBM alone but did reduce PA-related dyspnea and difficulty. Clinical trial registered with www.clinicaltrials.gov (NCT02085161).
RCT Entities:
RATIONALE: Bronchodilation and exercise training (ExT) improve exercise tolerance in patients with chronic obstructive pulmonary disease (COPD); however, behavior modification is required to impact daily physical activity (PA). OBJECTIVES: To assess whether tiotropium/olodaterol, with or without ExT, would improve exercise endurance time (EET) and PA compared with placebo in patients participating in a self-management behavior-modification (SMBM) program. METHODS: This was a 12-week, randomized, partially double-blind, placebo-controlled, parallel-group trial in patients with COPD (PHYSACTO; NCT02085161). All patients were enrolled into SMBM and randomized 1:1:1:1 to once-daily placebo, tiotropium 5 μg, tiotropium/olodaterol 5/5 μg, or tiotropium/olodaterol 5/5 μg plus 8 weeks ExT. EET, measured by endurance shuttle walk test after 8 weeks, was the primary endpoint. Additional endpoints assessed downstream effects on PA (measured via accelerometry), and activity-related dyspnea and difficulty (using validated patient-reported questionnaires). MEASUREMENTS AND MAIN RESULTS:SMBM plus tiotropium/olodaterol, with or without ExT, significantly improved EET at Week 8 versus SMBM plus placebo (treatment ratio vs. placebo: with ExT, 1.46; 95% confidence interval, 1.20-1.78; P = 0.0002; without ExT, 1.29; 95% confidence interval, 1.06-1.57; P = 0.0109). No significant increases in steps per day from baseline were observed over SMBM plus placebo at Week 12 (increase of 1,098) when other therapies were added. Adding tiotropium/olodaterol, with or without ExT, to SMBM reduced activity-related dyspnea versus placebo, whereas adding tiotropium/olodaterol plus ExT reduced activity-related difficulty. CONCLUSIONS:Tiotropium/olodaterol, with or without ExT, improved EET in patients with COPD taking part in an SMBM program. Combination bronchodilation, with or without ExT, did not provide additional increases in objective PA compared with SMBM alone but did reduce PA-related dyspnea and difficulty. Clinical trial registered with www.clinicaltrials.gov (NCT02085161).
Entities:
Keywords:
dyspnea; exercise capacity; tiotropium/olodaterol; walking test
Authors: Wassim W Labaki; Lucas M Kimmig; Gökhan M Mutlu; MeiLan K Han; Surya P Bhatt Journal: Am J Respir Crit Care Med Date: 2019-06-15 Impact factor: 21.405
Authors: Imran Satia; Mohammad Abdul Malik Farooqi; Ruth Cusack; Masanobu Matsuoka; Xie Yanqing; Om Kurmi; Paul M O'Byrne; Kieran J Killian Journal: Physiol Rep Date: 2020-04
Authors: Christian R Osadnik; Matthias Loeckx; Zafeiris Louvaris; Heleen Demeyer; Daniel Langer; Fernanda M Rodrigues; Wim Janssens; Ioannis Vogiatzis; Thierry Troosters Journal: Int J Chron Obstruct Pulmon Dis Date: 2018-10-24