Wahlgren 1999

Methods	Randomized, double‐blind, multicenter, placebo‐controlled study to test the efficacy and safety of the neuroprotective drug chlormethiazole for acute stroke
Participants	Participants aged 40 to 90 years with full consciousness before treatment were included. The symptoms should have lasted more than 1 hour and less than 12 hours. SSS‐48 of ≦ 40, with a sum of scores on arm, hand and leg motor items of ≦ 14. 1360 eligible participants from 85 clinical centers in 7 European countries and Canada were randomized; 546 participants had TACS and 95 participants had hemorrhagic stroke
Interventions	Chlormethiazole (75 mg/kg) or placebo were given as an intravenous infusion over a 24‐hour period
Outcomes	Independence (BI ≧ 60); SSS‐48; SSS‐MP; adverse events; mortality
Notes	Follow‐up: 3 months
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomization was stratified by center, but the method of random sequence generation was not described
Allocation concealment (selection bias)	Low risk	All validations were made with the treatment allocation blinded
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Only the independent data monitoring committee had access to unblinded data during the course of the study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Only the independent data monitoring committee had access to unblinded data during the course of the study
Incomplete outcome data (attrition bias) All outcomes	Low risk	16/1360 (1%) randomized participants did not complete the study. 4 participants did not receive treatment (1 randomized to chlormethiazole, 3 to placebo). 4/1360 (0.3%) randomized participants were not available for the safety analysis. In subgroup analyses, data from 1/95 (1%) randomized hemorrhagic stroke participants and 6/546 (1%) randomized TACS participants were not available for analysis
Selective reporting (reporting bias)	Low risk	All pre‐specified outcomes were reported
Other bias	Low risk	No other bias was found

BI: Barthel Index score CT: computerized tomography iv: intravenous MRI: magnetic resonance imaging mRS: modified Rankin Scale NIHSS: National Institutes of Health Stroke Scale SSS‐48: 48‐point Scandinavian Stroke Scale SSS‐MP: Scandinavian Stroke Scale motor power score t‐PA: tissue‐type plasminogen activator TACS: total anterior circulation syndrome