Apixaban versus antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intracerebral haemorrhage in patients with atrial fibrillation. A randomised phase II clinical trial.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 101

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) non-valvular 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.
The clinical equipoise should be self-reported by the attending neurologist
after reviewing the all relevant information available for the individual
patient.
Age * 18 years.
Written informed consent by the patient or by a healthcare proxy

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 when 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 (see protocol chapter 7.1.4) 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 *mol 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

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The combination of vascular death or non-fatal stroke (cerebral infarction,<br /><br>intracerebral haemorrhage, or subarachnoid haemorrhage) during follow-up.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Vascular death.<br /><br>Death from any cause.<br /><br>All stroke.<br /><br>Ischaemic stroke.<br /><br>Intracerebral haemorrhage.<br /><br>Other major extracranial haemorrhage<br /><br>Any intracranial haemorrhage other than ICH.<br /><br>Systemic embolism.<br /><br>Myocardial infarction.<br /><br>Functional outcome as assessed with the score on the modified Rankin Scale at 6<br /><br>and 12 months; thereafter annually and at the end of the study.</p><br>

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