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The study evaluates the effects of antithrombotic drugs (anticoagulant drugs or antiplatelet drugs) for prevention of ischaemic events in patients With recent intracerebral haemorrhage.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Antithrombotic treatment | Experimental | For patients with vascular disease and indication for antiplatelet drugs: Antiplatelet drugs; For patients with atrial fibrillation and indication for anticoagulant drugs: Anticoagulant drugs |
|
| No antithrombotic treatment | No Intervention | For patients with indication for antiplatelet drugs: No antithrombotic drugs For patients with atrial fibrillation and indication for anticoagulant drugs: No anticoagulant drugs. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Antithrombotic Agent | Drug | Anticoagulant or antiplatelet drugs |
|
| Measure | Description | Time Frame |
|---|---|---|
| Fatal or non-fatal symptomatic ICH. | Neurological deterioration or death associated with intracerebral haemorrhage found on CT scan, MRI, or autopsy. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Functional outcome | Modified Rankin Scale score | 2 years |
| Death of any cause | Death of any cause | 2 years |
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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.:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Torgeir Bruun Wyller, PhD | Oslo University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Herlev Gentofte Hospital | Copenhagen | DK-2730 | Denmark | |||
| Oslo University Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34022170 | Derived | Li L, Poon MTC, Samarasekera NE, Perry LA, Moullaali TJ, Rodrigues MA, Loan JJM, Stephen J, Lerpiniere C, Tuna MA, Gutnikov SA, Kuker W, Silver LE, Al-Shahi Salman R, Rothwell PM. Risks of recurrent stroke and all serious vascular events after spontaneous intracerebral haemorrhage: pooled analyses of two population-based studies. Lancet Neurol. 2021 Jun;20(6):437-447. doi: 10.1016/S1474-4422(21)00075-2. | |
| 34022160 |
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IPD will be shared within the COCROACH Collaboration.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 21, 2021 | Aug 30, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 28, 2024 | Aug 30, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D002543 | Cerebral Hemorrhage |
| D020300 | Intracranial Hemorrhages |
| D001281 | Atrial Fibrillation |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D005343 | Fibrinolytic Agents |
| ID | Term |
|---|---|
| D050299 | Fibrin Modulating Agents |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
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Randomised-controlled trial, parallel groups
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| Vascular death | Death of vascular cause | 2 years |
| Symptomatic epidural, subdural, or subarachnoid haemorrhage | Neurological deterioration or death associated with epidural, subdural, or subarachnoid haemorrhage found on CT scan, MRI, or autopsy. | 2 years |
| Symptomatic major extracranial haemorrhage | Clinically overt bleeding associated with one or more of:
| 2 years |
| Ischaemic events | 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. | 2 years |
| Oslo |
| 0424 |
| Norway |
| Umeå University Hospital | Umeå | SE-90185 | Sweden |
| Derived |
| Cheng X, Dong Q. Towards individualised secondary prevention after intracerebral haemorrhage. Lancet Neurol. 2021 Jun;20(6):411-413. doi: 10.1016/S1474-4422(21)00130-7. No abstract available. |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002317 | Cardiovascular Agents |
| D045506 | Therapeutic Uses |
| D006401 | Hematologic Agents |