RESTART 2019.

Study characteristics
Methods	Design: randomised controlled PROBE parallel group trial Setting: multicentre at 122 hospitals in the UK Dates: 22 May 2013 to 31 May 2018
Participants	Sample size: 537 participants Diagnosis: ICH Inclusion criteria Patient age ≥ 18 years Spontaneous primary or secondary ICH Patient had taken antithrombotic drug(s) for the prevention of vaso‐occlusive disease before ICH onset Randomisation > 24 hours after ICH onset Patient and their doctor are uncertain about whether to start or avoid antiplatelet drugs Patient is registered with a general practitioner Brain imaging that first diagnosed the ICH is available Participant or representative consent Brain MRI substudy: MRI done after ICH but before randomisation Exclusion criteria ICH due to preceding trauma or haemorrhagic transformation of ischaemic stroke Patient is taking an anticoagulant drug following ICH Patient is pregnant, breastfeeding, or of childbearing age and not taking contraception Patient is being treated or followed up in another CTIMP Patient and carer unable to understand spoken or written English Brain MRI substudy: no claustrophobia. MRI not contraindicated Age(years, median (IQR)): 77 (69–82) in the intervention group versus 76 (69–82) in the comparator group Sex (male): 173 (65%) in the intervention group versus 187 (70%) in the comparator group
Interventions	Intervention: one or more of oral aspirin, dipyridamole, or clopidogrel, begun within 24 hours of randomisation with doses determined at the discretion of the consultant responsible for the participant Comparator: policy of avoiding antiplatelet medication
Outcomes	Primary outcome Fatal or non‐fatal radiographically or pathologically proven recurrent symptomatic ICH Secondary outcome measures Composite of all major haemorrhagic events (recurrent symptomatic ICH, other forms of symptomatic spontaneous or traumatic intracranial haemorrhage, and symptomatic major extracranial haemorrhage at any site (requiring transfusion or endoscopic treatment or surgery, or resulting in death within 30 days)) Composite of all major occlusive vascular events (ischaemic stroke; myocardial infarction; mesenteric ischaemia; peripheral arterial occlusion; DVT; PE; and carotid, coronary, or peripheral arterial revascularisation procedures) Composite of all major haemorrhagic or occlusive vascular events (as defined above) Protocol‐defined composite secondary outcome of all major vascular events defined by the Antithrombotic Trialists’ Collaboration (non‐fatal myocardial infarction, non‐fatal stroke (ischaemic, haemorrhagic, or uncertain cause), or death from a vascular cause) Duration of follow‐up: at least 6 months (1064 person‐years)
Notes	Declarations of interest: RA‐SS and GDM report a grant from the British Heart Foundation (SP/12/2/29422) paid to the University of Edinburgh for the conduct of RESTART. RA‐SS reports grants from The Stroke Association, Chest Heart and Stroke Scotland, and GE Healthcare Limited, outside the submitted work. DEN reports grants and personal fees from AstraZeneca, Eli Lilly, Bristol Myers Squibb, and Jansen, during the conduct of the study. PAGS reports funding from Bayer outside the submitted work. NS reports a grant from National Institute for Health Research (NIHR) Health Technology Assessment for the TICH‐2 trial, outside the submitted work. JMW reports grants from EU Framework 7, Medical Research Council, and the British Heart Foundation, outside the submitted work. DJW reports personal fees from Bayer and JFB consulting, outside the submitted work. PMW reports personal fees from Stryker Global Advisory Board on Haemorrhagic Stroke and MicroVention‐Terumo, and a grant from MicroVention‐Terumo outside the submitted work. WNW reports a Chief Scientist Office of the Scottish Government Health Department Senior Fellowship (SCAF_17_01) and a grant from the European Stroke Organisation, outside the submitted work. MSD, JS, and CLMS declare no competing interests. Sources of funding: British Heart Foundation
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computerised randomisation system with minimisation algorithm
Allocation concealment (selection bias)	Low risk	The web interface displayed each participant’s unique study identification number and their allocation to either starting or avoiding antiplatelet therapy, which was also sent in an email to all investigators at the hospital site, having been concealed until that point
Blinding of participants and personnel (performance bias) All outcomes	High risk	Treatment allocation was open to the clinicians caring for patients in primary and secondary care, and local investigators and to participants
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome adjudication was blinded to treatment allocation and receipt of antiplatelet therapy during follow‐up
Incomplete outcome data (attrition bias) All outcomes	Low risk	Only 1 (0.2%) participant withdrew from follow‐up
Selective reporting (reporting bias)	Low risk	All pre‐specified outcomes were reported