Anticoagulation in ICH Survivors for Stroke Prevention and Recovery

Study Overview
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Brief Summary
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Primary Aim: To determine if apixaban is superior to aspirin for prevention of the composite outcome of any stroke (hemorrhagic or ischemic) or death from any cause in patients with recent ICH and atrial fibrillation (AF). Secondary Aim: To determine if apixaban, compared with aspirin, results in better functional outcomes as measured by the modified Rankin Scale.

Detailed Description
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ASPIRE is a randomized, double-blinded, phase III clinical trial designed to test the efficacy and safety of anticoagulation, compared with aspirin, in patients with a recent ICH and non-valvular AF. Seven hundred patients will be enrolled over 3.5 years and followed for study outcomes for a minimum of 12 months and maximum of 36 months. The primary efficacy outcome is any stroke (hemorrhagic or ischemic) or death from any cause. The secondary efficacy outcome is the change in the modified Rankin Scale score. Recruitment will take place at sites coordinated through the NIH/NINDS StrokeNet.

Official Title
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Anticoagulation in Intracerebral Hemorrhage (ICH) Survivors for Stroke Prevention and Recovery

Conditions
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Intracerebral Hemorrhage, Atrial Fibrillation

Intervention / Treatment
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* Drug: Apixaban
* Drug: Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at least 18 years Intracerebral hemorrhage (ICH) (including primary intraventricular hemorrhage) confirmed by brain CT or MRI Can be randomized within 14-180 days after ICH onset Non-valvular AF (defined as atrial fibrillation or atrial flutter), documented by electrocardiography or a physician-confirmed history of prior AF Provision of signed and dated informed consent form by patient or legally authorized representative For females of reproductive potential: use of highly effective contraception Exclusion Criteria: Index event is hemorrhagic transformation of a brain infarction or hemorrhage into a tumor History of earlier ICH within 12 months preceding index event Active infective endocarditis Clear indication for anticoagulant drugs (e.g., requires anticoagulation for deep vein thrombosis or pulmonary embolism) or antiplatelet drugs (e.g., requires aspirin or clopidogrel for recent coronary stent). Previous or planned left atrial appendage closure Clinically significant bleeding diathesis Serum creatinine ≥2.5 mg/dL Active hepatitis or hepatic insufficiency with Child-Pugh score B or C Anemia (hemoglobin <8 g/dL) or thrombocytopenia (<100 x 10^9/L) that is chronic in the judgment of the investigator Pregnant or breastfeeding Known allergy to aspirin or apixaban Concomitant participation in a competing trial Considered by the investigator to have a condition that precludes safe or active participation in the trial Persistent, uncontrolled systolic blood pressure (≥180 mm Hg) ICH caused by an arteriovenous malformation (AVM) that has not yet been secured

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Apixaban<br>Apixaban dosing will be 5 mg tablet in morning and 5 mg tablet in evening. A reduced dose of 2.5 mg tablet in morning and 2.5 mg tablet in evening will be used if: (1) ≥2 of the following are present: age ≥80 years, body weight ≤60 kg, or serum creatinine 1.5-2.4 mg/dL, or (2) Patient is taking a strong CYP3A4/pGP inhibitor (e.g., ketoconazole, itraconazole, ritonavir, or clarithromycin). | Drug: Apixaban<br>* Apixaban is an oral anticoagulant of the Factor Xa inhibitor class.<br>* Other names: Eliquis;|
| Placebo Comparator: Aspirin<br>Aspirin dose will be 81 mg tablet once daily. | Drug: Aspirin<br>* Aspirin is an oral antiplatelet drug.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stroke or death | Incidence of stroke of any type (ischemic or hemorrhagic) or death from any cause | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin Scale (mRS) score | Measure of neurologic disability (0=no disability to 6=dead) | Change from baseline to 12 months; change over duration of follow-up |