Methods	Study design: a randomised, double-blind, multicentre, parallel-group study over 12 weeks from November 2004 to June 2005 at 12 outpatient respiratory clinics in Europe (Poland (6) Ukraine (6)). Run-in 2 weeks
Participants	Population: 228 adults (18 to 65) years with moderate to severe persistent asthma. Baseline characteristics: mean age 48 years. FEV1 67% predicted. Concomitant inhaled corticosteroids used by 100% of participants. Average ICS dose 731 μg/day (BDP equivalent). Run in on ICS alone (no other anti-asthma medication permitted) Inclusion criteria: clinical diagnosis of moderate to severe persistent asthma for at least 6 months, FEV1 % predicted between 50% to 80%, bronchodilator reversibility by an increase of at least 12% in FEV1 (or, alternatively, of 200 ml) over baseline measured 30 min after 2 puffs (2 × 100 μg) of inhaled salbutamol administered via pMDI. Treated with ICS at a daily dose of less than 1000 μg of BDP-equivalent and had asthma symptoms not adequately controlled as defined by: presence of daily symptoms at least once a week, night-time symptoms at least twice a month and daily use of short-acting beta2-agonists. Exclusion criteria: COPD, current or ex-smokers (more than 10 pack-years); severe asthma exacerbation or symptomatic infection of the airways in the previous 8 weeks; more than 3 courses of oral corticosteroids or hospitalisation due to asthma in the previous 6 months; treatment with LABAs, anticholinergics or antihistamines in the previous 2 weeks, and/or with topical or intranasal corticosteroids and leukotriene antagonists in the previous 4 weeks, change of ICS dose in the previous 4 weeks
Interventions	1. Beclomethasone/formoterol 100/6 μg × 2 bd 2. Fluticasone/salmeterol 125/25 μg × 2 bd Delivery was via pMDI
Outcomes	The primary outcome variable was morning predose PEF measured by patients in the last 2 weeks of treatment period (weeks 11 and 12). No serious adverse events reported in either arm of the trial and the absence of deaths and hospitalisations has been confirmed by Chiesi; no details of one of the patients withdrawn due to “Development of an exclusion criteria”
Notes	Sponsored by Chiesi
Risk of bias
Bias	Authors’ judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was in balanced-block design stratified by centres
Allocation concealment (selection bias)	Low risk	“Each patient was identified with a randomisation number, from 001 to 260 (in blocks of four); each investigator assigned the lowest available randomisation number at each site.”
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Described as double-blind but not double-dummy and inhalers were different shape and size but this was “masked” using a non-removable external covering for the inhalers
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Described as double-blind but not double-dummy and inhalers were different shape and size but this was “masked” using a non-removable external covering for the inhalers
Incomplete outcome data (attrition bias) All outcomes	Low risk	225/228 (99%) completed the study
Selective reporting (reporting bias)	Low risk	“During the study no deaths or hospitalizations occurred.” Data on file at Chiesi
Independent Outcome Assessment Asthma-related serious adverse events	High risk	No independent outcome assessment