Neuro Trials

AF due to reversible causes (e.g. thyrotoxicosis, pericarditis, recent surgery, myocardial infarct)

Valvular disease requiring surgery

Mechanical heart valve(s)

Moderate or severe rheumatic mitral stenosis. Participants with other valvular diseases and biological valves are eligible

Conditions other than AF that require anticoagulation, including therapeutic doses of low-molecular-weight heparin or heparin

Anticoagulation above the relevant thresholds at ischaemic stroke onset or at hospital admission as follows:
o vitamin K antagonist: International Normalized Ratio (INR) ⩾ 1.7, or
o anti-IIa: thrombin time ⩾80 s and/or anti-IIa ⩾ 100 ng/ml and/or aPTT value >1.5× normal, or
o anti-Xa: anti-Xa ⩾ 100 ng/ml or ⩾0.7 U/ml

Contraindications to DOACs

Females with a positive pregnancy test at time of randomisation, a suspicion of pregnancy, or lactating

Patients with serious bleeding in the last 6 months or at high risk of bleeding (e.g. active peptic ulcer disease, platelet count < 100 000/mm3 or haemoglobin <10 g/dl or INR ⩾ 1.7, documented haemorrhagic tendencies or blood dyscrasias)

Subject currently uses or has a recent history of illicit use of drug(s) or abuses alcohol

Severe comorbid condition with life expectancy <6 months

Severe renal impairment as described in the summary of medicinal product characteristics for the chosen DOAC (e.g. rivaroxaban, apixaban and edoxaban creatinine clearance <15 ml/min; dabigatran creatinine clearance <30 ml/min)

Patient requires haemodialysis or peritoneal dialysis

Patient with aortic dissection

Current participation in another investigational trial

Dual antiplatelet therapy (DAPT) at baseline or a strong likelihood of being treated with DAPT during the course of the trial. Transient DAPT is not an exclusion criterion if it is stopped prior to randomisation.

CT or MRI evidence of haemorrhage classified as PH1 (defined as parenchymal haemorrhage = blood clots in <30% of the infarcted area with or without slight space-occupying effect) and PH2 (defined as blood clots in >30% of the infarcted area with a substantial space-occupying effect) independently of clinical deterioration. HI1 (defined as haemorrhagic infarct = small petechiae along the margins of the infarct) and HI2 (defined as confluent petechiae within the infarcted area but no space-occupying effect) are acceptable if not associated with clinical deterioration and if the treating physician feels comfortable about treating these patients with DOACs.

CT or MRI evidence of mass effect or intracranial tumour (except small meningioma)

CT or MRI evidence of cerebral vasculitis

Endocarditis

Evidence of severe cerebral amyloid angiopathy if MRI scan performed.