Anticoagulant-Induced Bleeding, Atrial Fibrillation, Cerebral Hemorrhage, Intracranial Hemorrhages, Secondary Prevention
Conditions
Keywords
Intracerebral hemorrhage
Brief summary
The study evaluates the effects of antithrombotic drugs (anticoagulant drugs or antiplatelet drugs) for prevention of ischaemic events in patients With recent intracerebral haemorrhage.
Detailed description
Patients with spontaneous ICH have an increased risk of recurrent ICH and they also have an increased risk of ischaemic diseases. Around 40-50% of patients use, or have an indication, for antithrombotic drugs at the time of ICH. However, little is known about the benefits and harms of using antithrombotic drugs for prevention of ischaemic events in patients who have had an ICH. There are only observational studies addressing this question. Because of the lack of randomised-controlled trials and the inconclusive findings of the observational studies, guidelines have variably endorsed both starting and avoiding antithrombotic drugs after ICH. The investigators therefore want to study the effect and safety of using antithrombotic drugs after ICH. Furthermore, since findings on MRI can be biomarkers for subsequent bleeding, there will also be performed a sub-study of the association between such findings on MRI and risk of recurrent ICH during treatment with antithrombotic drugs. Patients with ICH during the last 6 months and with an indication for antithrombotic drugs will be included. Patients with vascular disease and indication for antiplatelet drugs will be randomised to antiplatelet treatment vs. no antithrombotic treatment. Patients with atrial fibrillation and indication for anticoagulant treatment will be randomised to anticoagulant treatment vs. no anticoagulant treatment. The follow up period is 2 years, and the primary effect variable is new ICH. The investigators will also assess new intracranial haemorrhage, extracranial haemorrhage and ischemic events, and functional and cognitive outcome.
Interventions
Anticoagulant or antiplatelet drugs
Sponsors
Oslo University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Randomised-controlled trial, parallel groups
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient age ≥18 years. * Spontaneous, primary ICH, of ≥1 day, but not more than 180 days after onset of qualifying ICH, i.e.: * No preceding traumatic brain injury, based on history from the patient/witness of spontaneous symptom onset, and brain imaging appearances consistent of spontaneous ICH (i.e. any brain/bone/soft tissue appearances of trauma must have occurred secondary to a spontaneous ICH) * No 'secondary' or underlying structural cause (e.g. haemorrhagic transformation of an ischaemic stroke, aneurysm, tumour, arteriovenous malformation, or intracerebral venous thrombosis) * Patient have indication for antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of ischaemic events, either antiplatelet drugs (for patients with vascular disease), or anticoagulant drug for patients with atrial fibrillation. * Consent to randomisation from the patient (or personal / legal / professional representative if the patient does not have mental capacity). * MRI (or CT) is performed before randomisation.
Exclusion criteria
* Clear indication for antiplatelet or anticoagulant treatment (e.g. prosthetic heart valves). * Contraindications to the antithrombotic drug that will be administered. * Patient is pregnant, breastfeeding, or of childbearing age and not taking contraception. * For patients examined with MRI: Contraindication for brain MRI * Malignancy with life expectancy less than 2 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fatal or non-fatal symptomatic ICH. | 2 years | Neurological deterioration or death associated with intracerebral haemorrhage found on CT scan, MRI, or autopsy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Death of any cause | 2 years | Death of any cause |
| Vascular death | 2 years | Death of vascular cause |
| Functional outcome | 2 years | Modified Rankin Scale score |
| Symptomatic major extracranial haemorrhage | 2 years | Clinically overt bleeding associated with one or more of: * Transfusion of \>2 red cell units of blood * A fall in haemoglobin of 2 g/dL, (1.24 mmol/L) * Bleeding into retroperitoneum, intraocular space or major joint * Bleeding leading to permanent treatment cessation |
| Ischaemic events | 2 years | Transient ischaemic attack, ischaemic stroke, unstable angina, acute myocardial infarction (type 1), peripheral arterial occlusion, mesenteric ischaemia, retinal arterial occlusion, deep vein thrombosis or pulmonary embolism. |
| Symptomatic epidural, subdural, or subarachnoid haemorrhage | 2 years | Neurological deterioration or death associated with epidural, subdural, or subarachnoid haemorrhage found on CT scan, MRI, or autopsy. |
Countries
Denmark, Norway, Sweden
Outcome results
None listed