title: Dual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: the BLAZE study.
abstract: We evaluated the effect of QVA149, a dual bronchodilator combining indacaterol and glycopyrronium, on direct patient-reported dyspnoea in patients with moderate-to-severe chronic obstructive pulmonary disease. In this multicentre, blinded, double-dummy, three-period crossover study, 247 patients were randomised to once-daily QVA149 110/50 μg, placebo or tiotropium 18 μg. Superiority of QVA149 versus placebo (primary objective) and tiotropium (secondary objective) was assessed for improvement in dyspnoea via the self-administered computerised (SAC) version of the Baseline and Transition Dyspnoea Index after 6 weeks. Secondary end-points included lung function, rescue medication use and safety. After 6 weeks, the SAC Transition Dyspnoea Index total score was significantly higher with QVA149 versus placebo (least squares mean (LSM) treatment difference 1.37, p<0.001) and tiotropium (LSM treatment difference 0.49, p=0.021). QVA149 provided significant improvements in lung function, with higher forced expiratory volume in 1 s area under the curve from 0-4 h post-dose 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). All treatments were well tolerated. Once-daily QVA149 provided superior improvements in patient-reported dyspnoea and lung function versus placebo and tiotropium. These benefits were associated with improvements in other symptoms and reduced use of rescue medication.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA Donald.A.Mahler@hitchcock.org.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Mahler
authors.affiliation: Division of Respiratory Medicine, University Hospital, Katholieke Universiteit, Leuven, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Decramer
authors.affiliation: Dept of Family and Community Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: D'Urzo
authors.affiliation: Dept of Pneumology and Cardiology, Hospital Fürth, University Erlangen-Nürnberg, Fürth, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Worth
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: White
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Vijay K T
authors.initials: VK
authors.lastname: Alagappan
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Hungta
authors.initials: H
authors.lastname: Chen
authors.affiliation: Novartis Horsham Research Centre, Horsham, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Gallagher
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Károly
authors.initials: K
authors.lastname: Kulich
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Banerji
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004338:Drug Combinations; D004417:Dyspnea / Q000150:complications* / Q000188:drug therapy*; 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; D011208:Powders; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000188:drug therapy*; 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; D011208:Powders; D015363:Quinolones; D012602:Scopolamine Derivatives; C554862:indacaterol-glycopyrronium combination; D006024:Glycopyrrolate; D000069447:Tiotropium Bromide