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.

Conflict of interest statement

Conflict of interest: Disclosures can be found alongside the online version of this article at www.erj.ersjournals.com

Figures

Figure 1–

The SHINE study design.

Figure 2–

Flow diagram for disposition of patients. Data are presented as n (%), unless otherwise stated. #: nine patients were randomised but did not receive the study drug (n = 5: major protocol deviation for an inclusion/exclusion criteria (did not meet electronic diary inclusion criteria); n = 1: patient did not meet spirometry criteria; n = 1: patient withdrew consent; n = 1: patient took tiotropium during visit 3; n = 1: site had issues with the MasterScope® (eResearch Technology, Inc, Philadelphia, PA, USA) and could not continue); ¶: for each treatment group, the full analysis and safety sets comprised the same patients.

Figure 3–

Trough forced expiratory volume in 1 s (FEV1) a) at week 26 and b) over the entire 26-week treatment period. a) Data are presented as least squares mean±se. One-sided adjusted p-values are presented for comparisons in the statistical gatekeeping procedure and two-sided p-values are presented for all other comparisons. b) QVA149 was superior to all active treatments and placebo at all timepoints (all p<0.001). n: number per treatment group in the full analysis set.

Figure 4–

Serial spirometry on a) day 1 and b) week 26. a) QVA149 was superior to placebo and tiotropium at all assessed timepoints (p1: forced expiratory volume in 1 s.