Bateman 2013.
| Methods |
Design: multi‐centre, randomised, double‐blind, parallel‐group, placebo‐controlled trial. 26‐week duration. Additional bronchodilators other than albuterol were discontinued. Inhaled corticosteroids were continued at the same dose. Efficacy outcomes were analysed on an intention‐to‐treat basis. Safety outcomes were analysed according to the treatment received. Patients were recruited from research centres in Europe, North America, South America, Asia, Australia, China, Taiwan and South Africa Run‐in:14 days |
|
| Participants |
Population: 2144 participants with stable moderate to severe COPD by GOLD criteria were randomly assigned (QVA149 110/50 (glycopyrronium/indacaterol) 475, indacaterol 477, glycopyrronium 475, tiotropium 483, placebo 234). Predominantly male population (75.4%). Mean age of 64 years. Predominantly Caucasian and Asian population. Most participants had moderate COPD by GOLD criteria. QVA149, indacaterol, glycopyrronium, tiotropium and placebo arms (57.8%, 56.5%, 57.9%, 58.8% and 57.8%) were taking concomitant inhaled corticosteroids respectively. Mean FEV1 was 54% to 55% predicted across all experimental arms Inclusion criteria: adults > 39 years with stable GOLD stage 2 or 3 (by 2008 criteria) COPD and at least a 10‐pack‐year smoking history, postbronchodilator FEV1/FVC < 70% (400 mcg salbutamol), FEV1 < 80% but >29% Exclusion criteria: pregnant women or women of childbearing potential, history of medication intolerance to any of the classes of trial medications, history of long QT syndrome or QTc > 450 seconds or other clinically significant ECG abnormalities, uncontrolled diabetes, narrow‐angle glaucoma, prostatic hyperplasia, bladder neck obstruction or moderate to severe chronic kidney disease, malignancy within previous 5 years, requirement for long‐term oxygen therapy, exacerbation within the previous 6 weeks or lower respiratory tract infection within 4 weeks, previous lung surgery, history of asthma, active participation in pulmonary rehabilitation |
|
| Interventions | 1. Indacaterol/Glycopyrronium (QVA149) 110/50 mcg 2. Indacaterol 150 mcg 3. Glycopyrronium 50 mcg 4. Open‐label tiotropium 18 mcg 5. Placebo |
|
| Outcomes | Primary outcome: trough FEV1 at 26 weeks for QVA 149 vs its mono components Secondary outcomes: QVA149, indacaterol and glycopyrronium versus placebo, 26‐week TDI and SGRQ scores, rescue medication use, health status, participant symptoms, safety and tolerability, cardiovascular safety, other lung function endpoints |
|
| Notes | Study funded by Novartis and Novartis employees contributed to manuscript preparation | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation via interactive response technology (IRT) |
| Allocation concealment (selection bias) | Low risk | IRT linked the participant to a treatment arm with a unique medication number for the study drug. Randomisation data remained strictly confidential and inaccessible to anyone involved in the study until the time of unbinding |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Identity of treatments was concealed by identical packaging, labelling, schedule of administration, appearance, taste and colour. Tiotropium was open‐label. Bioanalysts of pharmacokinetic samples were unblinded |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Outcome assessors were blinded to treatment allocation |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Rates and reasons for dropouts were clearly reported. Higher rate of dropout from the placebo arm than from other treatment arms was due to protocol deviation, consent withdrawal and unsatisfactory therapeutic effect |
| Selective reporting (reporting bias) | Low risk | Primary and secondary outcomes were reported |