Effect of lung deflation with indacaterol plus glycopyrronium on ventricular filling in patients with hyperinflation and COPD (CLAIM): a double-blind, randomised, crossover, placebo-controlled, single-centre trial

Summary Background Pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) is associated with reduced biventricular end-diastolic volumes and increased morbidity and mortality. The combination of a long-acting β agonist (LABA) and a muscarinic antagonist (LAMA) is more effective in reducing hyperinflation than LABA–inhaled corticosteroid combination therapy but whether dual bronchodilation improves cardiac function is unknown. Methods We did a double-blind, randomised, two-period crossover, placebo-controlled, single-centre study (CLAIM) at the Fraunhofer Institute of Toxicology and Experimental Medicine (Hannover, Germany), a specialty clinic. Eligible participants were patients aged at least 40 years with COPD, pulmonary hyperinflation (defined by a baseline residual volume >135% of predicted), a smoking history of at least ten pack-years, and airflow limitation (FEV 1 1 : forced vital capacity Findings Between May 18, 2015, and April 20, 2017, we randomly assigned 62 eligible participants to treatment; 30 to indacaterol–glycopyrronium followed by placebo and 32 to placebo followed by indacaterol–glycopyrronium. The 62 randomly assigned patients were included in the intent-to-treat analysis. There were two protocol violations and therefore 60 were included in the per-protocol analysis. 57 patients completed both treatment periods. After indacaterol–glycopyrronium treatment, left-ventricular end-diastolic volume increased from a mean 55·46 mL/m 2 (SD 15·89) at baseline to a least-squares (LS) mean of 61·76 mL/m 2 (95% CI 57·68–65·84), compared with a change from 56·42 mL/m 2 at baseline (13·54) to 56·53 mL/m 2 (52·43–60·62) after placebo (LS means treatment difference 5·23 mL/m 2 [95% CI 3·22 to 7·25; p Interpretation This is the first study to analyse the effect of LABA–LAMA combination therapy on cardiac function in patients with COPD and lung hyperinflation. Dual bronchodilation with indacaterol–glycopyrronium significantly improved cardiac function as measured by left-ventricular end-diastolic volume. The results are important because of the known association of cardiovascular impairment with COPD, and support the early use of dual bronchodilation in patients with COPD who show signs of pulmonary hyperinflation. Funding Novartis Pharma GmbH.