PREVENTIHS 2020.

Study characteristics
Methods	Design: parallel group RCT Setting: multicentre at hospitals in Italy Dates: 1 May 2016 to 30 March 2020
Participants	Sample size: 73 participants Diagnosis: ICH Inclusion criteria Bedridden (score of 3 or 4 on item 6 of the NIHSS or the impossibility to maintain an upright position such as in the case of ataxia in patients with haemorrhagic cerebellar stroke) 18 years of age or older Spontaneous ICH on CT scan or intracranial haemorrhage during treatment with oral anticoagulants (after reversal)  > 72 hours after symptom onset Exclusion criteria 10% increase in ICH volume between diagnostic CT and CT performed before randomisation at 72 hours after symptom onset. ICH due to vascular malformation SAH  Subdural haematoma Bleeding disorders (defined by a prothrombin time > 30% longer than the control value or a platelet count of < 100,000 per mm3) Renal failure defined as a creatinine clearance of < 30 Severe hepatic failure Known neoplastic disease Pregnancy Need for therapeutic anticoagulant or antiplatelet agents for concomitant disease Participation in other ongoing clinical trials Patient refusal to consent Age (years, mean (SD)): 70 +/‐14 (intervention) versus 72 +/‐ 12 (comparator) Sex: 22/38 (intervention) versus 18/35 (comparator) were male
Interventions	Intervention: enoxaparin 0.4mL (4000 units) once daily for 10 days ± 1 day plus standard therapy (38 participants) Comparator: standard therapy alone (35 participants)
Outcomes	Primary outcome Symptomatic VTE objectively documented as proximal/distal DVT or PE, or asymptomatic proximal/distal DVT documented by ultrasound at 10 days Secondary outcomes Any VTE at 90 days Any increase of 10% or more in the baseline ICH volume Major extracranial haemorrhage (the presence in critical organ sites including the retroperitoneal and intraocular spaces, a reduction of 2 or more g/dL of haemoglobin, the need to carry out a transfusion of 2 or more units of concentrate red blood cells, or fatal bleeding) Death or disability (mRS ≥ 3) at 90 days Death at 90 days Duration: CT brain and venous eco‐color‐Doppler examination with a compression test performed bilaterally on the lower limbs 10 +/‐ 1 day following the start of treatment. Clinical follow‐up was done 90 days after randomisation
Notes	Declarations of interest: Maurizio Paciaroni ‐ member of the speaker bureau of Sanofi‐Aventis, Boehringer Ingelheim, Bayer, Bristol Meyer Squibb, Daiichi Sankyo, and Pfizer. Giancarlo Agnelli ‐ member of the speaker bureau of Boehringer Ingelheim and Bayer. Cecilia Becattini ‐ member of the speaker bureau of Bristol Meyer Squibb and Bayer. Valeria Caso ‐ received honoraria as a member of the speaker bureau and as consultant or advisory board of Boehringer Ingelheim. Walter Ageno ‐ received speaker’s honoraria from, and participated in scientific advisory boards for, Boehringer Ingelheim, Bayer, Bristol‐Myers Squibb/Pfizer, and Daiichi Sankyo, and has received research support from Bayer and Boehringer Ingelheim Sources of funding: Ministero della Salute (Health Minister) of the Italian Government (n. FARM12L9JE) Other: this trial was stopped prematurely because of slow recruitment
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were centrally randomised over the phone using a random list of numbers (even numbers – treatment A; odd numbers – treatment B) closed in an envelope."
Allocation concealment (selection bias)	Unclear risk	Quote: "Patients were centrally randomised over the phone using a random list of numbers (even numbers – treatment A; odd numbers – treatment B) closed in an envelope."  It is not clear if the envelopes were opaque
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open label (participants and personnel were aware of allocated treatment)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	All outcome assessment was described as being blinded to treatment allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	All data for randomised participants were reported
Selective reporting (reporting bias)	Low risk	All planned outcomes were reported
Other bias	Unclear risk	Premature termination due to slow recruitment