Szafranski 2003.
Methods | Design: randomised, double‐blind, placebo‐controlled, parallel‐group, multi‐centre study Duration: 12 months (+ 2 weeks run‐in period) Location: 89 centres from 11 countries | |
Participants |
Population: 812 participants were randomised to formoterol (201), budesonide (198), formoterol/budesonide combination (208), and placebo (205) Baseline characteristics Age (mean years): form 63, bud 64, form/bud 64, pbo 65 % Male: form 76, bud 80, form/bud 76, pbo 83 % FEV1 predicted: form 36, bud 37, form/bud 36, pbo 36 Pack‐years (mean): form 45, bud 44, form/bud 44, pbo 45 Inclusion criteria: males and females aged 40 and older; symptoms for 2+ years; history of at least 10 pack‐years Exclusion criteria: history of asthma or seasonal rhinitis before 40 years of age; relevant cardiovascular disorders; use of beta‐blockers; current respiratory tract disorders other than COPD or any other significant diseases or disorders; requiring regular use of oxygen therapy; exacerbation during run‐in |
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Interventions | 1. Formoterol 12 bid (LABA) 2. Budesonide 400 bid (ICS) 3. Formoterol/budesonide 9/320 bid (LABA/ICS) 4. Placebo (PBO) Inhaler device: Dry powder turbuhaler Allowed co‐medications: terbutaline (0.5 mg) as reliever. Disallowed medication included parenteral steroids, oral steroids, antibiotics and nebulised treatment from 4 weeks before; inhaled steroids from 2 weeks before; inhaled long‐acting beta2‐agonists from 48 hours before; inhaled short‐acting beta2‐agonists from 6 hours before; other bronchodilators from 6 to 48 hours before |
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Outcomes | St George's Respiratory Questionnaire (SGRQ), COPD exacerbations, FEV1, vital capacity, morning and evening PEF, diary card data | |
Notes | Funding: AstraZeneca Identifier(s): AZ SD‐039‐CR‐0629 | |
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | A total of 812 patients were randomised [no other details, industry sponsored] |
Allocation concealment (selection bias) | Unclear risk | No details provided |
Blinding of participants and personnel (performance bias) All outcomes | Low risk | Double‐blind [presumed subject and investigator] |
Blinding of outcome assessment (detection bias) All outcomes | Low risk | No details provided. Inlcuded outcomes unlikely to be affected by detection bias |
Incomplete outcome data (attrition bias) All outcomes | High risk | Withdrawal high and uneven between groups (formoterol 31.8%, placebo 43.9%). An intention‐to‐treat analysis was used. |
Selective reporting (reporting bias) | High risk | Quality of life [primary] stated as outcome but not reported in enough detail to include in meta‐analysis. |