| Study characteristics |
| Methods |
Design: randomised controlled PROBE parallel group (2:1) phase 2 trial
Setting: multicentre at 8 hospitals in Canada
Dates: April 2017 to May 2019 |
| Participants |
Sample size: 30 participants
Diagnosis: ICH
Inclusion criteria
Exclusion criteria
Non‐stroke absolute indication for antiplatelet or anticoagulant therapy Recent ICH within 14 days Platelet count less than 100,000/mm3 at enrollment or other bleeding diathesis Prior symptomatic lobar ICH other than the qualifying event Uncontrollable hypertension consistently above SBP/DBP of 160/100 mmHg Known hypersensitivity to either aspirin or NOACs Inability to adhere to study procedures Pregnant or breastfeeding Unexpected to survive 6 months
Age(years, mean (SD)): 77.7 (SD 9.2) intervention versus 75.8 (SD 5.5) comparator
Sex (male): 12/21 (57%) intervention versus 5/9 (56%) comparator |
| Interventions |
Intervention: NOAC (apixaban or dabigatran or edoxaban or rivaroxaban) and BP control to target < 130/80mmHg (21 participants)
Comparator: acetylsalicylic acid 81 mg/day and BP control to target < 130/80mmHg (9 participants) |
| Outcomes |
Primary outcomes
Secondary outcomes
Refusal (average number of eligible patients per site who refuse consent) Retention (randomised patients who completed 6 months of follow‐up on drug or died during trial participation) Ischaemic stroke (acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute ischaemic stroke) ICH (a neurologic deficit associated with an ICH or IVH on CT or MRI scan, or as demonstrated by surgery or autopsy) Fatal stroke (due to ischaemic stroke or ICH) Myocardial infarction All‐casue mortality Systemic thromboembolism (emboli to the arterial circulation excluding myocardial infarction, ischaemic stroke or ICH) Major haemorrhage (bleeding accompanied by one or more of the following ‐ a decrease in the haemoglobin level of ≥ 20 g per litre over a 24‐hour period, transfusion of ≥ 2 units of packed red cells, bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, or retroperitoneal), or fatal bleeding) Intracranial haemorrhage (signs or symptoms associated with an epidural, subdural, subarachnoid, ICH or IVH on CT or MRI scan, or as demonstrated by surgery or autopsy) Composite of all stroke, myocardial infarct, systemic thromboembolism or death mRS MOCA Weighted net clinical benefit (weighted net clinical benefit factoring the impact of ischaemic stroke, ICH, non‐intracerebral intracranial haemorrhage, major extracranial haemorrhage and myocardial infarction on death and disability)
Duration of follow‐up: mean 1.53 years (SD 0.54) |
| Notes |
Declarations of interest: Daiichi Sankyo Ltd, Bayer AG, Octapharma Canada, Portola pharmaceuticals, BMS/Pfizer, Servier Canada Inc
Sources of funding: not specified. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Personal correspondence with the chief investigator confirmed that central, web‐based randomisation was used, with allocation concealment |
| Allocation concealment (selection bias) |
Low risk |
Personal correspondence with the chief investigator confirmed that central, web‐based randomisation was used, with allocation concealment |
| Blinding of participants and personnel (performance bias)
All outcomes |
High risk |
Open‐label |
| Blinding of outcome assessment (detection bias)
All outcomes |
Low risk |
Assessor‐blind |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
100% complete follow‐up |
| Selective reporting (reporting bias) |
Low risk |
All pre‐specified outcomes were reported |
