Tashkin 2012.
Methods | Design: randomised, double‐blind, placebo‐controlled trial Duration: 6 months (+ 2 weeks run‐in period) Location: 131 centres located in South America, Asia, Africa, Europe and North America | |
Participants |
Population: 1055 participants were randomised to formoterol (209), mometasone (210), two doses of formoterol/mometasone combination (217 and 207), and placebo (212) Baseline characteristics Age (mean years): form 59.6, mom 59.8, form/mom400 59.7, form/mom200 60.9, pbo 58.8 % Male: form 72.7, mom 78.1, form/mom400 78.8, form/mom200 77.8, pbo 80.2 % FEV1 predicted: not reported Pack‐years (mean): form 40.3, mom 40.0, form/mom400 39.7, form/mom200 41.7, pbo 40.3 Inclusion criteria: males and females aged 40 and older; history of at least 10 pack‐years; moderate to severe COPD for at least 2 years; predicted FEV1 between 25% and 60% normal Exclusion criteria: exacerbation in the four weeks before randomisation; significant medical illness; diagnosis of asthma, lung cancer or alpha1‐antitrypsin deficiency, lobectomy, pneumonectomy, lung volume reduction surgery or ocular problems |
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Interventions | 1. Formoterol 10 bid (LABA) 2. Mometasone 400 bid (ICS) 3. Formoterol/mometasone 10/400 bid (LABA/ICS) 4. Formoterol/mometasone 10/200 bid (LABA/ICS) 5. Placebo (PBO) Inhaler device: metered dose Allowed co‐medications: Participants were given open‐label, short‐acting beta2‐agonist (SABA)/short‐acting anticholinergic fixed‐dose combination to use as relief medication throughout the study. All long‐acting COPD treatments (LABA, ICS, LABA/ICS FDC or long‐acting anticholinergics), supplemental oxygen and beta‐blocking agents were not allowed during the study period |
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Outcomes | St George's Respiratory Questionnaire (SQRQ), reported as both final scores and the number of people experiencing a MCID (improvement or worsening by 4 units), COPD exacerbations, serial FEV1 post‐dose, standardised FEV1 area under the curve, systemic and ocular effects | |
Notes | Funding: Merck & Co/Schering‐Plough Identifier(s): NCT00383435 | |
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | The sponsor’s statistician produced a computer‐generated randomisation schedule with treatment codes in blocks using SAS. Randomisation was stratified according to the subject’s smoking status at the time of randomisation. |
Allocation concealment (selection bias) | Low risk | Randomized treatment assignment was provided to the investigative site by means of an interactive voice response system at the time subjects were randomized. |
Blinding of participants and personnel (performance bias) All outcomes | Low risk | Protocol describes the study masking as double‐blind (subject, investigator) |
Blinding of outcome assessment (detection bias) All outcomes | Low risk | Protocol describes the study masking as double‐blind (subject, investigator) |
Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Withdrawal rates 17.7% in formoterol and 25% in the placebo group, unclear methods of imputation for some outcomes |
Selective reporting (reporting bias) | High risk | Can't extract FEV1 (table 3), other outcomes poorly reported for the comparison used in this review |