Treatment with apixaban or an antiplatelet drug or no antithrombotic drugs after a brain hemorrhage when using medication to prevent a stroke due to a clot in patients with atrial fibrillation.

Phase 1

• Conditions: The prevention of ischaemic stroke in patients with atrial fibrillation; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2014-000112-33-NL
• Lead Sponsor: niversity Medical Center Utrecht

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-07-07
• Last Update Posted: 22 March 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Intracerebral haemorrhage (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) AF, documented on electrocardiography.
A CHA2DS2VASc score = 2. The item Stroke in the Stroke/TIA/TE item refers to ischaemic stroke, not haemorrhagic stroke.
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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion Criteria

Conditions other than atrial fibrillation for which the patient requires long-term anticoagulation.
A different clinical indication for the use of an APD 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 or haemoglobin level of <6.2 mMol/L, 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 an 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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 hemorrhage who are treated with apixaban versus those who are treated with antiplatelet drugs or no antithrombotics.;Secondary Objective: To compare the rates of all cause death, disabling stroke, major haemorrhage, systemic embolism and functional outcome between patients treated with apixaban and those who are treated with antiplatelet drugs or no antithrombotics..;Primary end point(s): The combination of vascular death or non-fatal stroke (cerebral infarction, intracerebral haemorrhage, or subarachnoid haemorrhage) during follow-up.;Timepoint(s) of evaluation of this end point: Entire study duration.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Vascular death.<br>Death from any cause. <br>All stroke.<br>Ischaemic stroke.<br>Intracerebral haemorrhage. <br>Other major extracranial haemorrhage<br>Any intracranial haemorrhage other than ICH. <br>Systemic embolism.<br>Myocardial infarction. <br>Functional outcome as assessed with the score on the modified Rankin Scale at 6 and 12 months; thereafter annually and at the end of the study.<br>;Timepoint(s) of evaluation of this end point: Entire study duration.<br>Functional outcome: at 6, 12, and 24 months and at the end of the study.