Tashkin 2008 [SHINE].
| Methods | Design: randomised, double‐blind, double‐dummy, placebo‐controlled, parallel‐group, multicenter study Duration: 6 months (+ 2 weeks run‐in period) Location: 194 centres in the USA, Czech Republic, the Netherlands, Poland and South Africa | |
| Participants |
Population: 1704 participants were randomised to formoterol (284), budesonide (275), three doses of formoterol/budesonide combination (281, 277 and 287, one of which was not included in the review as they were delivered in separate inhalers), and placebo (300) Baseline characteristics Age (mean years): form 63.5, bud 63.4, form/bud160 63.6, 1form/bud320 63.1, pbo 63.2 % Male: form 65.5, bud 67.6, form/bud160 64.4, 1form/bud320 67.9, pbo 69 % FEV1 predicted: form 39.6, bud 39.7, form/bud160 39.9, 1form/bud320 39.1, pbo 41.3 Pack‐years (median): form 40, bud 41, form/bud160 40, 1form/bud320 40, pbo 40 Inclusion criteria: male and female current or former smokers; history of at least 10 pack‐years; clinical diagnosis of COPD; 40+ years; symptoms for longer than 2 years; at least one exacerbation treated with oral corticosteroids and/or antibacterials within 1 to 12 months before screening Exclusion criteria: history of asthma or seasonal rhinitis before age 40; significant/unstable cardiovascular disorder; significant respiratory tract disorder other than COPD; homozygous alpha1‐antitrypsin deficiency or other clinically significant co‐morbidities precluding participation |
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| Interventions | 1. Formoterol 12 bid (LABA) 2. Budesonide 320 bid (ICS) 3. Formoterol/budesonide 9/160 bid in one inhaler (LABA/ICS) 4. Formoterol/budesonide 9/320 bid in one inhaler (LABA/ICS) 5. Placebo (PBO) Inhaler device: dry powder Allowed co‐medications: Allowed medications were ephedrine‐free antitussives and mucolytics; nasal corticosteroids; stable‐dose non‐nebulised ipratropium; cardioselective beta‐adrenoceptor antagonists; salbutamol as rescue; oral steroids, xanthines, inhaled beta‐agonists and ipratropium as medication for exacerbations. Medications disallowed during the study period were long‐acting anticholinergics; inhaled LABAs or SABAs (other than salbutamol); oral beta‐adrenoreceptor agonists; ephedrine; leukotriene receptor agonists and xanthine derivatives except for short‐term use |
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| Outcomes | St George's Respiratory Questionnaire (SGRQ) including number of people reaching threshold for minimal clinically important difference from baseline (4 units), COPD exacerbations per patient year, pre‐dose fFEV1 and 1‐hour post‐dose FEV1, dyspnoea, morning and evening PEF | |
| Notes | Funding: AstraZeneca Identifier(s): NCT00206154, AZ D5899C00002 | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Eligable patients were randomized in balanced blocks according to a computer‐generated randomisation scheme at each site |
| Allocation concealment (selection bias) | Unclear risk | No information provided |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | To maintain blinding, patients received both a pressurized metered‐dose inhaler (pMDI) and a dry powder inhaler (DPI) containing either active treatment or placebo (PL), or combinations of active treatment and placebo, as appropriate |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | ECG results were evaluated by a cardiologist in a blinded fashion through an independent ECG service provider |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Withdrawal rates were similar (21.5% formoterol, 25.7% placebo) and 'the efficacy analysis set included all randomised patients who received at least one dose of study medication and contributed sufficient data for at least one co‐primary or secondary efficacy endpoint' |
| Selective reporting (reporting bias) | Low risk | All stated outcomes were reported in full and included in the quantitative synthesis |