S2BM03.

Methods	Multicentre, randomised, double‐blind, placebo‐controlled, cross‐over study Each participant received 2 doses; 1 of either sumatriptan or placebo at the onset of migraine and the other at 4 h Assessments at 1, 2, 4, 5, 6, and 72 h after dosing Five optional open‐label doses of sumatriptan 6 mg were available from 6 to 72 h for the treatment of recurrent headache, although no more than 2 doses of sumatriptan were permitted in any 24 h period Rescue medication was permitted from 6 h after the first dose of study medication. No further open‐label sumatriptan was permitted if rescue medication was used.
Participants	Aged 18 to 65, meeting IHS criteria for migraine (1988) with or without aura. At least 1‐year history of migraine (untreated severity ≥ moderate) with a frequency of 1 to 6 attacks per month. Participants required to have a history of attacks (≥ 50% of attacks) that progressed from mild to moderate or severe intensity in ≤ 60 minutes from attack onset In addition participants had to have used sumatriptan regularly for at least 6 months before study entry and experience recurrence in ≥ 50% of attacks treated with sumatriptan At least a 48 h washout period (sumatriptan‐free) required between the 2 treated attacks No ergotamine‐containing prophylactic medication, or use of monoamine oxidase inhibitors, 5‐hydroxtryptamine reuptake inhibitors, or lithium during the study period N = 120 (90 treated both attacks and provided cross‐over efficacy data) M 13, F 77 (86%) Mean age 45 years Proportion with/without aura not reported
Interventions	Sumatriptan 6 mg (+ placebo at 4 h), n = 106 (90 for cross‐over efficacy analysis, of which 87 had moderate or severe baseline pain intensity) Placebo (+ sumatriptan 6 mg at 4 h), n = 106 (90 for cross‐over efficacy analysis, of which 81 had moderate or severe baseline pain intensity)
Outcomes	Headache relief (at 1 and 2 h) Pain‐free (at 1 and 2 h) Presence of nausea, vomiting, and photo/phonophobia (at 1 and 2 h) Improvement in functional disability (at 1 and 2 h) Serious adverse events Withdrawals
Notes	Oxford Quality Score: R1, DB1, W1. Total = 3.
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	Unclear risk	Not reported
Study size	Unclear risk	Treatment groups 50 to 200 participants