De Reuck 1995.

Methods	Double blind randomised placebo controlled trial. Participants were randomised to treatment or placebo groups using a computer generated randomisation schedule stratified by study centre. Results were analysed by intention to treat, missing data were estimated by the last available score. No details are available about whether assessors were blinded to the treatment status of the participants. Participants or relatives provided written consent.
Participants	927 people, from 55 hospitals in 10 European countries, of which 373 were aphasic and were analysed separately from the others (placebo group n=193, treatment group n= 180). The age range of participants was 40 to 80 years (the mean age of aphasic people was 72.9 years). All had been admitted to hospital with a clinical diagnosis of an acute ischaemic supratentorial stroke. People entered the study if arousable, and if their symptoms within the preceding 12 hours were judged disabling on the Orgogozo scale (Orgogozo 1986). The diagnosis was confirmed by one or two CT scans. Exclusion criteria: A scan showing first evidence of cerebral haemorrhage and significant midline shift Significant stupor or coma A previous stroke with clinical sequelae Confounding neurologic or systemic illness Dipyridamole and ticlopidine were prohibited during the first 4 weeks of the study. Concomitant aspirin was not recommended for at least 24 hours after the stroke. Thrombolytic agents, haemodilution and drugs acting on cerebral vasculature were forbidden throughout. Specific entry criteria for the aphasic patients: People were only admitted whose mother tongue was the same as the language of the presented FAST (Enderby 1987) test version, and who could read before the stroke. People were deemed to be aphasic if they scored 13/20 or less on the expression/comprehension subscales of the FAST scale (Enderby 1987).
Interventions	Piracetam 12 gram in bolus intravenously within 12 hours post stroke onset, followed by piracetam 12 gram per day intravenously until 4th day. Thereafter 12 gram piracetam per day orally until 4 weeks, then 4.8 gram per day for 8 weeks. Piracetam belongs to a unique pharmacologic class and has been suggested to act as both a neuroprotective and neurotropic agent.
Outcomes	Aphasic participants were assessed with the Frenchay Aphasia Test (FAST, Enderby 1987). Tests of neurological functioning (Orgogozo 1983), and behaviour (Barthel Index, Mahoney 1965) were also given, the analysis being performed on an intention‐to‐treat basis, with missing data estimated by the last available score. The authors report that a statistically significant difference was found in favour of the treated aphasic group on the FAST test at day 84 (the level of significance is variously reported in the papers written concerning this study). The authors also report that no statistically significant differences were found between the two groups on other parameters tested in the study population as a whole. However in a predefined sub‐group analysis of a group who were aphasic, and treated within 7 hours of the stroke, the authors reported statistically significant differences in language function on aphasia testing, and in other parameters of functioning at the end of the study period, in favour of the treated group. A post hoc analysis of the early treated group reportedly showed that those treated within 7 hours of the stroke performed better on treatment than on placebo if they were originally diagnosed as having a moderate to marked impairment. This difference in favour of piracetam did not apply to those with mild impairment. No difference in mortality rates was found for the population as a whole, and it is not possible to separate those who had an adverse event and died later, from those experiencing only an adverse event. Death rates for the aphasic participants are not reported separately. An economic analysis showed that total cost per participant was lower in the treated group than in the placebo group.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear