MASCOT 2013

Methods	A prospective, controlled, double‐blind, multi‐centre, randomised clinical trial lasting 48 weeks, with a 4‐week open run‐in
Participants	Population: 63 children aged 6 to 14 years with asthma uncontrolled on low‐dose ICSs were randomised Baseline characteristics: average age of children included was 10.39 years; 63.5% were male Inclusion criteria: children who required frequent short‐acting beta₂‐agonist relief therapy: ≥ 7 puffs in the past 7 days; children with symptoms of asthma (i.e. wheeze, shortness of breath but not cough alone) that resulted in (I) nocturnal wakening in the last week and/or (ii) interference with usual activities in the last week and/or (iii) exacerbations, defined as a short course of oral corticosteroids, an unscheduled general practitioner or accident and emergency (A&E) department visit, or a hospital admission within the past 6 months Exclusion criteria: children who received long‐acting beta₂‐agonists, leukotriene receptor antagonists, regular theophylline therapy, or high‐dose ICSs (> 1000 μg) and unlicensed beclomethasone dipropionate or equivalent (at the discretion of the investigator); also children with other respiratory diseases, cystic fibrosis, cardiac disease, or immunological disorders
Interventions	During the 4‐week run‐in period, all patients were commenced on fluticasone propionate inhalers (Flixotide, GSK) at 200 μg per day (100 μg twice daily). Children who remained symptomatic at the end of the run‐in period were randomised to 1 of 3 double‐blind treatment regimens. • Inhaled fluticasone propionate 100 μg and salmeterol 50 μg twice daily (combination inhaler) plus placebo tablet once daily • Inhaled fluticasone propionate 100 μg twice daily plus placebo tablet once daily • Inhaled fluticasone propionate 100 μg twice daily plus montelukast 5‐mg tablet once daily (this arm was not used in the review)
Outcomes	Primary outcome: number of asthma exacerbations requiring treatment with oral corticosteroids over the planned 48‐week study period Secondary outcomes: number of hospital admissions due to respiratory problems and adverse events
Notes	Funded by NIHR Health Assessment Technology Programme
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation code lists were generated (by an individual at the MCRN CTU who was not involved with the MASCOT trial) with the software package Stata (Release 9, StataCorp LP, College Station, TX, USA) using block randomisation with variable block length, stratified by secondary care centre, with allocation to the 3 treatment arms in the ratio 1:1:1
Allocation concealment (selection bias)	Low risk	The pharmacy at each secondary care centre held the randomisation list for that centre, with treatment allocations labelled A, B, and C. After determining a participant's treatment allocation from the list, the pharmacist selected an appropriate treatment pack and removed a serrated label showing A, B, or C before dispensing to the participant
Blinding (performance bias and detection bias) All outcomes	Low risk	Study drugs were identical in appearance and were identically packaged, with all patients, clinicians, and trial personnel blinded to treatment allocation throughout
Independent Assessment of causation (detection bias) Asthma‐related events	High risk	Independent assessment of causation was not clearly described
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Early trial closure due to difficulty in recruiting makes the effect of attrition bias due to the small sample size unclear
Selective reporting (reporting bias)	Low risk	Adverse events and hospitalisations were reported