Apixaban After Anticoagulation-associated Intracerebral Haemorrhage in Patients With Atrial Fibrillation

• Status: Completed
• Trial end date: 2021-01-31
• Target enrollment: 0
• Participant gender: All

Summary

There is a marked lack of evidence on the optimal prevention of ischaemic stroke in patients with atrial fibrillation and a recent intracerebral haemorrhage (ICH) during treatment with oral anticoagulation. These patients are currently treated with vitamin K antagonists, DOACs, antiplatelet drugs, or no antithrombotic treatment, depending on personal and institutional preferences. Treatment with a direct oral anticoagulant like apixaban might be an attractive alternative in terms of a low risk of recurrent ICH, while at the same time being effective for the prevention of ischaemic stroke. This study aims to obtain reliable estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage who are treated with apixaban versus those who are treated with antiplatelet drugs or no antithrombotic drug at all.

This study has a multi-centre, phase II, randomised, open-label clinical trial with blinded outcome assessment design.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: UMC Utrecht
• Collaborators: Dutch Heart Foundation; ZonMw: The Netherlands Organisation for Health Research and Development
• Treatments: Apixaban; Aspirin; Calcium; Carbaspirin calcium; Clopidogrel; Dipyridamole; Platelet Aggregation Inhibitors

Criteria

Inclusion Criteria:

• Intracerebral haemorrhage (including including isolated spontaneous intraventricular haemorrhage), documented with CT or MRI, during treatment with anticoagulation (VKA, any direct thrombin inhibitor, any factor Xa inhibitor, or (low molecular weight) heparin at a therapeutic dose).

• The haemorrhage has occurred between 7 and 90 days before randomization.

• Diagnosis of (paroxysmal) non-valvular AF, documented on electrocardiography.

• A CHA2DS2-VASc score ≥ 2.

• Score on the modified Rankin scale (mRS)≤4.

• Equipoise regarding the optimal medical treatment for the prevention of stroke.

• Age ≥ 18 years.

• Written informed consent by the patient or by a legal representative

Exclusion Criteria:

• Conditions other than atrial fibrillation for which the patient requires long-term anticoagulation

• A different clinical indication for the use of an antiplatelet drug even if treated with apixaban, such as clopidogrel for recent coronary stenting.

• Mechanical prosthetic heart valve (biological prosthetic heart valves are allowed) or rheumatic mitral valve disease.

• Serious bleeding event in the previous 6 months, except for intracerebral haemorrhage.

• High risk of bleeding (e.g., active peptic ulcer disease, a platelet count of <100,000.mL-1 or haemoglobin level of <6.2 mMol.L-1, ischaemic stroke in the previous 7 days (patients are eligible thereafter), documented haemorrhagic tendencies, or blood dyscrasias).

• Current alcohol or drug abuse.

• Life expectancy of less than 1 year.

• Severe renal insufficiency (a serum creatinine level of more than 221 μmol per liter or a calculated creatinine clearance of <15 ml per minute).

• Alanine aminotransferase or aspartate aminotransferase level greater than 2 times the upper limit of the normal range or a total bilirubin more than 1.5 times the upper limit of the normal range, unless a benign causative factor (e.g. Gilbert's syndrome) is known or identified.

• Allergy to apixaban.

• Use of strong cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) inhibitors (e.g. systemic azole-antimycotics as ketoconazole or HIV protease inhibitors such as ritonavir).

• Pregnancy or breastfeeding.

• Women of childbearing potential: any woman who has begun menstruation and is not postmenopausal or otherwise permanently unable to conceive. A postmenopausal woman is defined as a woman who is over the age of 45 and has not had a menstrual period for at least 12 months.