Efficacy and safety of once-daily QVA149 compared with the free combination of once-daily tiotropium plus twice-daily formoterol in patients with moderate-to-severe COPD (QUANTIFY): a randomised, non-inferiority study.
Buhl, Roland 1; Gessner, Christian 2,3; Schuermann, Wolfgang 4; Foerster, Karin 5; Sieder, Christian 6; Hiltl, Simone 6; Korn, Stephanie 7
[Article]
Thorax.
70(4):311-319, April 2015.
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Background: QVA149 is a once-daily (o.d.) inhaled dual bronchodilator containing a fixed-dose combination of the long-acting [beta]2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium for the treatment of COPD. The QUANTIFY study compared QVA149 with a free-dose bronchodilator combination of tiotropium plus formoterol (TIO FOR) in improving health-related quality of life (HRQoL) of patients with COPD.
Methods: This multicentre, blinded, triple-dummy, parallel-group, non-inferiority study randomised patients aged >=40 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s (FEV1) >=30% to <80% predicted) to QVA149 110/50 [micro]g o.d. or TIO 18 [micro]g o.d. FOR 12 [micro]g twice daily (1:1) for 26 weeks. The primary endpoint was to demonstrate non-inferiority in HRQoL assessed using St George's Respiratory Questionnaire-COPD (SGRQ-C). The prespecified non-inferiority margin was 4 units. Secondary endpoints included Transition Dyspnoea Index (TDI) score, pre-dose FEV1, forced vital capacity (FVC) and safety.
Results: Of the 934 patients randomised (QVA149=476 and TIO FOR=458), 87.9% completed the study. At week 26, non-inferiority was met for SGRQ-C (QVA149 vs TIO FOR; difference: -0.69 units; 95% CI -2.31 to 0.92; p=0.399). A significantly higher percentage of patients achieved a clinically relevant >=1 point improvement in TDI total score with QVA149 (49.6%) versus TIO FOR (42.4%; p=0.033). QVA149 significantly increased pre-dose FEV1 ( 68 mL, 95% CI 37 mL to 100 mL; p<0.001) and FVC ( 74 mL, 95% CI 24 mL to 125 mL; p=0.004) compared with TIO FOR at week 26. The incidence of adverse events was comparable between both treatments (QVA149=43.7% and TIO FOR=42.6%).
Conclusions: QVA149 is non-inferior to TIO FOR in improving HRQoL, with clinically meaningful and significant improvements in breathlessness and lung function in patients with COPD.
Trial registration number: NCT01120717.
(C) 2015 BMJ Publishing Group Ltd & British Thoracic Society