Burge 2000 [ISOLDE].

Methods	Design: Double blind, placebo controlled study Duration: 3 years Location: Conducted at 18 hospitals in the UK
Participants	Population: 751 people were randomised to fluticasone (376) and placebo (375) Baseline characteristics: Age (mean years): flut 63.7, placebo 63.8 Male %: flut 75.0, placebo 74.1 % FEV1 predicted: flut 50.3, placebo 50.0 Pack‐years (mean): flut 44, pbo 44 Inclusion criteria: Current or former smokers aged 40­75 years with non­asthmatic chronic obstructive pulmonary disease. Baseline FEV1 after bronchodilator was at least 0.8 litres but less than 85% of predicted normal, and the ratio of FEV1 to forced vital capacity was less than 70%. Previous use of inhaled and oral corticosteroids was permitted. Exclusion criteria: Patients were excluded if their FEV1 response to 400 µg salbutamol exceeded 10% of predicted normal, they had a life expectancy of less than five years from concurrent diseases, or they used beta blockers.
Interventions	1. Fluticasone 500 bid (ICS) 2. Placebo (PBO) Inhaler device: Metered dose inhaler with a spacer device Allowed co‐medications: Nasal and ophthalmic corticosteroids, theophyllines, and all other bronchodilators were allowed during the study
Outcomes	Decline (ml/year) in FEV1 after bronchodilator, frequency of exacerbations, changes in health status, withdrawals because of respiratory disease, morning serum cortisol concentrations, and adverse events
Notes	Funding: GlaxoWellcome Research and Development Identifier(s): unknown
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer generated allocation (block size of six)
Allocation concealment (selection bias)	Low risk	Patients were randomised sequentially from a list comprising treatment numbers only
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Three year double blind phase using an identical placebo inhaler
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	High risk	Very high dropout in both groups (43% and 53%)
Selective reporting (reporting bias)	Unclear risk	No outcomes appear to be missing but couldn't locate protocol to ensure all were reported. Author attempted contact with GSK statistician but no data were provided in time for publication.