Introduction QVA149, a novel once-daily inhaled dual bronchodilator combining a fixed dose of the long-acting β2 agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium, has demonstrated improvements in dyspnoea versus its mono-components (indacaterol and glycopyrronium), tiotropium, and salmeterol/fluticasone using the interviewer-based Transition Dyspnoea Index (TDI) questionnaire.1,2 The BLAZE study evaluated the effect of once-daily QVA149 on patient-reported dyspnoea versus placebo and blinded tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).
Methods This was a 6 week, multicentre, randomised, blinded, double-dummy, placebo-controlled, 3-period, cross-over study. Patients aged ≥40 years with moderate-to-severe COPD, post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥30% and <80% of the predicted normal, and post-bronchodilator FEV1/ forced vital capacity <0.7 were randomised to receive QVA149 110/50 μg (via the Breezhaler® device) or placebo (via the Breezhaler®/ HandiHaler® device) or blinded tiotropium 18 μg (via the HandiHaler® device). The primary objective of the study was to evaluate the superiority of QVA149 versus placebo in the improvement of patient-reported dyspnoea as assessed by Self-Administered Computerised (SAC) version of the Baseline Dyspnoea Index (BDI)/TDI after 6 weeks of treatment. Other objectives included; standardised FEV1 area under the curve from 0 to 4 hours post-dose (AUC0–4 h); rescue medication use; safety and tolerability.
Results Of the 247 patients (mean age 62.8 years) randomised, 191 completed the study. The SAC TDI total score was significantly improved with QVA149 compared with placebo and tiotropium after 6 weeks (figure). FEV1 AUC 0–4 h was significantly higher for QVA149 versus placebo and tiotropium at Day 1 and Week 6 (all p < 0.001). Rescue medication use was significantly lower with QVA149 versus placebo (p < 0.001) and tiotropium (p = 0.002). Incidence rate of adverse events was similar across all the treatment groups (QVA 149: 35.0%; tiotropium: 35.5%; placebo: 39.4%).
Conclusion The BLAZE study provides evidence that the improved lung function with QVA149 translates into greater relief of breathlessness and improved patient-reported outcomes.
Bateman et al. Eur Respir J. 2013 May 30.
Vogelmeier et al. Lancet Respir Med. 2013; 1:51–60.