ABSTRACT
BACKGROUND: QVA149 is a once-daily (o.d.) inhaled dual bronchodilator containing a fixed-dose combination of the long-acting ß2-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 ≥40â years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1â s (FEV1) ≥30% to <80% predicted) to QVA149 110/50â µg o.d. or TIO 18â µg o.d.+ FOR 12â µg twice daily (1:1) for 26â 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 (+68â mL, 95% CI 37â mL to 100â mL; p<0.001) and FVC (+74â mL, 95% CI 24â mL to 125â 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.
Subject(s)
Bronchodilator Agents/therapeutic use , Ethanolamines/therapeutic use , Glycopyrrolate/analogs & derivatives , Indans/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Quinolones/therapeutic use , Scopolamine Derivatives/therapeutic use , Adrenergic beta-2 Receptor Agonists/administration & dosage , Adrenergic beta-2 Receptor Agonists/adverse effects , Adrenergic beta-2 Receptor Agonists/therapeutic use , Aged , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/adverse effects , Double-Blind Method , Drug Administration Schedule , Drug Combinations , Ethanolamines/administration & dosage , Ethanolamines/adverse effects , Female , Forced Expiratory Volume/drug effects , Formoterol Fumarate , Glycopyrrolate/administration & dosage , Glycopyrrolate/adverse effects , Glycopyrrolate/therapeutic use , Humans , Indans/administration & dosage , Indans/adverse effects , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/physiopathology , Quality of Life , Quinolones/administration & dosage , Quinolones/adverse effects , Scopolamine Derivatives/administration & dosage , Scopolamine Derivatives/adverse effects , Tiotropium Bromide , Treatment Outcome , Vital Capacity/drug effectsABSTRACT
BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often experience symptoms and problems with activities early in the morning. This is the first study to compare the effect of budesonide/formoterol and salmeterol/fluticasone on lung function, symptoms and activities early in the morning. METHODS: Lung function (peak expiratory flow [PEF] and forced expiratory volume in 1 second [FEV( 1)]) and symptoms were measured at bedside and activities were measured during the morning using a six-item questionnaire concerning basic morning routines. In a randomised, double-blind, multicentre, cross-over study, 442 patients with COPD aged >or=40 years (pre-bronchodilator FEV(1) Subject(s)
Anti-Inflammatory Agents/therapeutic use
, Bronchodilator Agents/therapeutic use
, Pulmonary Disease, Chronic Obstructive/drug therapy
, Activities of Daily Living
, Adult
, Aged
, Aged, 80 and over
, Albuterol/adverse effects
, Albuterol/analogs & derivatives
, Albuterol/therapeutic use
, Androstadienes/adverse effects
, Androstadienes/therapeutic use
, Anti-Inflammatory Agents/adverse effects
, Bronchodilator Agents/adverse effects
, Budesonide/adverse effects
, Budesonide/therapeutic use
, Cross-Over Studies
, Double-Blind Method
, Drug Combinations
, Ethanolamines/adverse effects
, Ethanolamines/therapeutic use
, Female
, Fluticasone-Salmeterol Drug Combination
, Forced Expiratory Volume
, Formoterol Fumarate
, Humans
, Male
, Middle Aged
, Respiratory Function Tests
, Surveys and Questionnaires