Dual bronchodilation with QVA149 versus single bronchoditator therapy: the SHINE study

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 mu g/glycopyrronium 50 mu g), indacaterol 150 mu g, glycopyrronium 50 mu g, open-label tiotropium 18 mu g 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 beta(2)-agonist combinations for the treatment of COPD.