Clinical trial NCT03186729: Study of Antithrombotic Treatment After IntraCerebral Haemorrhage
Official title: Study of Antithrombotic Treatment After IntraCerebral Haemorrhage
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Cerebral Hemorrhage
Intracranial Hemorrhages
Atrial Fibrillation
Anticoagulant-Induced Bleeding
Secondary Prevention
Keywords: Intracerebral hemorrhage
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
First posted: 2017-06-14
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised-controlled trial, parallel groups
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Fatal or non-fatal symptomatic ICH.
timeFrame: 2 years
Secondary outcomes:
measure: Functional outcome
timeFrame: 2 years
measure: Death of any cause
timeFrame: 2 years
measure: Vascular death
timeFrame: 2 years
measure: Symptomatic epidural, subdural, or subarachnoid haemorrhage
timeFrame: 2 years
measure: Symptomatic major extracranial haemorrhage
timeFrame: 2 years
measure: Ischaemic events
timeFrame: 2 years
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Herlev Gentofte Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Umeå
country: Sweden
facility: Umeå University Hospital
Study officials:
affiliation: Oslo University Hospital
name: Torgeir Bruun Wyller, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.