IST 1997.

Study characteristics
Methods	Concealment: telephone randomisation Unblinded; dependency assessment mainly blinded Exclusions during trial: none Losses to follow‐up: 2 at 14 days (1 treatment, 1 control); 150 at 6 months (81 treatment, 69 control)
Participants	International 19,435 participants 54% male 61% aged > 70 years 67% CT prior to randomisation, 29% CT after randomisation Ischaemic stroke < 48 hours since stroke onset
Interventions	Treatment 1: subcutaneous heparin (5000 IU or 12,500 IU 12 hourly) Treatment 2: aspirin 300 mg Treatment 3: subcutaneous heparin (5000 IU or 12,500 IU 12 hourly) + aspirin 300 mg Control: no treatment (factorial design) Duration: 14 days or until discharge from hospital Aspirin by mouth if able to swallow, if not then by rectal suppository or by injection of 100 mg of the lysine salt of aspirin
Outcomes	Death Functional outcome (validated simple questions) Recurrent stroke Pulmonary embolus (symptomatic) Intracranial haemorrhage (symptomatic CT) Extracranial haemorrhage
Funding source	Principally funded by the UK Medical Research Council (who also funded P Sandercock, J Slattery, and B Farrell), the UK Stroke Association, and the European Union BIOMED‐1 programme. Support for collaborators' meetings and travel was provided by Eli Lilly, Sterling Winthrop (now Bayer USA), Sanofi, and Bayer UK. Follow‐up in Australia was supported by a grant from the National Heart Foundation to G Hankey. Follow‐up in Canada was supported by a Nova Scotia Heart and Stroke Foundation grant to S Phillips. Czech Republic IST was supported by a grant from the IGA Ministry of Health to Z Ambler. India IST was supported by the McMaster INCLEN program and the All India Institute of Medical Sciences. The IST in New Zealand was funded by the Julius Brendel Trust and the Lottery Grants Board. The IST was supported in Norway by the Norwegian Council on Cardiovascular Disease and Nycomed (for insurance).
Notes	Exclusions: small likelihood of worthwhile benefit; high risk of AE (e.g. hypersensitivity of aspirin, recent GI bleed or peptic ulcer disease, already on long‐term anticoagulation) Follow‐up: 6 months
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Central randomisation service at clinical trial service used.
Allocation concealment (selection bias)	Low risk	Computer allocated based on a minimisation algorithm.
Blinding of participants and personnel (performance bias) all outcomes	Unclear risk	Participants and personnel were not blinded, but the authors stated lack of blinding probably did not affect the main findings for the primary outcomes.
Blinding of outcome assessment (detection bias) all outcomes	Unclear risk	No blinding of the outcome assessment, but the authors stated lack of blinding probably did not affect the main findings for the primary outcomes.
Incomplete outcome data (attrition bias) all outcomes	Low risk	Outcome data were 99.99% complete for 14‐day follow‐up and 99.2% complete for 6‐month follow‐up.
Selective reporting (reporting bias)	Low risk	Study protocol available.
Other bias	Low risk	No sources of other bias identified.