Anticoagulation in Intracerebral Hemorrhage (ICH) Survivors for Stroke Prevention and Recovery
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Yale University
- Enrollment
- 700
- Locations
- 337
- Primary Endpoint
- Stroke or death
Study Overview
Brief Summary
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
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Apixaban
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).
Intervention: Apixaban (Drug)
Aspirin
Aspirin dose will be 81 mg tablet once daily.
Intervention: Aspirin (Drug)
Outcomes
Primary Outcomes
Stroke or death
Time Frame: Up to 3 years
Incidence of stroke of any type (ischemic or hemorrhagic) or death from any cause
Secondary Outcomes
- Modified Rankin Scale (mRS) score(Change from baseline to 12 months; change over duration of follow-up)