Kavuru 2000

Methods	A randomised, double‐blind, double‐dummy, parallel‐group, placebo‐controlled study over 12 weeks at 42 centres in the USA. Run‐in 2 weeks single‐blind placebo
Participants	Population: 356 adolescents and adults (12 to 70 years) with asthma Baseline characteristics: mean age 37 years; FEV₁ 64% predicted Concomitant ICS used by 100% of participants in group 1 and 0% of participants in group 2  Inclusion criteria: at least 12 years old with medical history of asthma (as defined by the ATS) of at least 6 months' duration; FEV₁ % predicted between 40% and 85%; bronchodilator reversibility by an increase ≥ 15%  in FEV₁ over baseline 30 minutes after 2 puffs (180 μg)  of inhaled albuterol Stratified into 2 groups according to type of asthma therapy used at enrolment  Exclusion criteria: history of life‐threatening asthma; hypersensitivity reaction to sympathomimetic drugs or corticosteroids; smoking within the previous year or a history of > 10 pack‐years; use of oral, inhaled, or injectable corticosteroid therapy within previous month; use of intranasal corticosteroid therapy except for Flonase (GlaxoWellcome Inc.); use of daily oral corticosteroid treatment within previous 6 months; use of any other prescription or over‐the‐counter medication that could have affected the course of asthma or interacted with sympathomimetic amines; abnormal chest x‐ray films; clinically significant abnormal 12‐lead electrocardiograms (ECGs); or a history of significant concurrent disease (e.g. glaucoma, diabetes, hypertension)
Interventions	• Fluticasone propionate and salmeterol 100/50 μg twice daily • Fluticasone 100 μg  twice daily Delivery was Diskus inhaler
Outcomes	Mean morning pre‐dose FEV₁ at endpoint; area under 12‐hour serial FEV₁ curve relative to baseline after I week of treatment (mean FEV₁ AUC); probability of remaining in the study over time without withdrawal due to lack of efficacy Paper reports no serious drug‐related adverse events and reports 2 serious adverse events that led to withdrawal. Website records 2 events on fluticasone propionate/salmeterol and 1 event on fluticasone propionate. (Unclear whether the 2 fluticasone propionate/salmeterol events occurred in separate participants, so treated as 1 participant)
Notes	Sponsored by GSK
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blind, double‐dummy
Independent Assessment of causation (detection bias) Asthma‐related events	High risk	Causation of SAEs not independently assessed
Incomplete outcome data (attrition bias) All outcomes	Low risk	142/182 (78%) completed the study
Selective reporting (reporting bias)	Low risk	Data available on GlaxoSmithKline website