title: Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study.
abstract: We investigated the efficacy and safety of dual bronchodilation with QVA149 versus its monocomponents indacaterol and glycopyrronium, tiotropium and placebo in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). This was a multicentre, randomised, double-blind, placebo- and active-controlled, 26-week trial. Patients (n = 2144) were randomised (2:2:2:2:1) to receive once-daily QVA149 (indacaterol 110 μg/glycopyrronium 50 μg), indacaterol 150 μg, glycopyrronium 50 μg, open-label tiotropium 18 μg or placebo. The primary end-point was trough forced expiratory volume in 1 s (FEV1) at week 26 for QVA149 versus its monocomponents. Secondary end-points included dyspnoea, health status, rescue medication use and safety. Trough FEV1 at week 26 was significantly improved (p<0.001) with QVA149 compared with indacaterol and glycopyrronium (least squares mean (LSM) differences 0.07 L and 0.09 L, respectively), tiotropium and placebo (LSM differences 0.08 L and 0.20 L, respectively); these beneficial effects were sustained throughout the 26-week study. QVA149 significantly improved dyspnoea and health status versus placebo (p<0.001 and p = 0.002, respectively) and tiotropium (p = 0.007 and p = 0.009, respectively) at week 26. All treatments were well tolerated. Dual bronchodilation with once-daily QVA149 demonstrated superior and clinically meaningful outcomes versus placebo and superiority versus treatment with a single bronchodilator, with a safety and tolerability profile similar to placebo, supporting the concept of fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist combinations for the treatment of COPD.
authors.affiliation: University of Cape Town, Cape Town, South Africa.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Bateman
authors.forename: Gary T
authors.initials: GT
authors.lastname: Ferguson
authors.forename: Neil
authors.initials: N
authors.lastname: Barnes
authors.forename: Nicola
authors.initials: N
authors.lastname: Gallagher
authors.forename: Yulia
authors.initials: Y
authors.lastname: Green
authors.forename: Michelle
authors.initials: M
authors.lastname: Henley
authors.forename: Donald
authors.initials: D
authors.lastname: Banerji
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005541:Forced Expiratory Volume; D006024:Glycopyrrolate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007189:Indans / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000008:administration & dosage*; D012602:Scopolamine Derivatives / Q000008:administration & dosage; D013147:Spirometry; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D004338:Drug Combinations; D007189:Indans; D015363:Quinolones; D012602:Scopolamine Derivatives; C554862:indacaterol-glycopyrronium combination; C510790:indacaterol; D006024:Glycopyrrolate; D000069447:Tiotropium Bromide