TRX109011/13.

Study characteristics
Methods	Multicentre, R, DB, DD, 3 phase cross‐over. Single dose of each medication to treat single attack. Washout between attacks ≥ 72 h Medication taken when pain ≥ moderate Assessments at 0, 2, 4, 6, 8, 24, 48 h
Participants	Migraine ± aura (IHS 2004), aged ≥ 18 years. History of 2 to 8 attacks per month in previous 3 months N = 375 attacks (ITT; 442 attacks for safety) F = 88% Mean age 43 years
Interventions	Sumatriptan 50 mg plus naproxen 500 mg, n = 406 (317 for efficacy) Paracetamol (acetaminophen) 325 mg + caffeine 40 mg + butalbital 50 mg, n = 392 (304 for efficacy) Placebo, n = 405 (320 for efficacy)
Outcomes	Headache relief at 2 h Pain‐free at 2 h 24‐h sustained headache relief 24‐h sustained pain‐free Presence and relief of functional disability at 2 h Use of rescue medication Mean time to first use of rescue medication AEs Withdrawals
Notes	Oxford Quality Score: R2, DB2, W1. Total = 5
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"computer‐generated block randomization schedule"
Allocation concealment (selection bias)	Unclear risk	Not described, but probably remote allocation
Blinding (performance bias and detection bias) All outcomes	Low risk	"3 identical tablets for each dose". DD method
Incomplete outcome data (attrition bias) All outcomes	Low risk	Drop‐outs described. All treated attacks accounted for
Study size	Low risk	> 200 participants per treatment arm

ACE: angiotensin‐converting enzyme; AE: adverse event; ARB: angiotensin receptor blocker; DB: double‐blind; DD: double dummy; h: hour; IHS: International Headache Society; ITT: intention to treat; MAOI: monoamine oxidase inhibitor; N: number of participants in study; n: number of participants in treatment arm; NSAID: non‐steroidal anti‐inflammatory drug; PC: placebo‐controlled; R: randomised; SJW: St John's Wort; W: withdrawals.