EdoxabaN foR IntraCranial Hemorrhage Survivors With Atrial Fibrillation (ENRICH-AF)
Purpose
To assess whether edoxaban (60/30 mg daily) compared to non-antithrombotic medical therapy (either no antithrombotic therapy or antiplatelet monotherapy) reduces the risk of stroke (composite of ischemic, hemorrhagic and unspecified stroke) in high-risk atrial fibrillation (CHA2DS2-VASc ≥2) patients with previous intracranial hemorrhage.
Conditions
- Intracranial Hemorrhages
- Atrial Fibrillation
Eligibility
- Eligible Ages
- Over 45 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Written informed consent provided 2. Age ≥45 years, at the time of signing the informed consent 3. Previous intracranial hemorrhage (symptomatic, spontaneous and non-traumatic non-lobar intraparenchymal or intraventricular hemorrhage, and symptomatic spontaneous or non-penetrating traumatic subdural hemorrhages) on or off antithrombotic therapy 4. Documented atrial fibrillation (paroxysmal, persistent, permanent) 5. CHA2DS2-VASc score ≥2
Exclusion Criteria
- Recent intracranial hemorrhage (within 14 days) 2. Secondary macrovascular, neoplastic or infectious causes of intracranial hemorrhage (except for antithrombotic treatment or non-penetrating traumatic subdural hemorrhages) 3. Isolated subarachnoid hemorrhage (convexity or basal); subarachnoid blood tracking onto convexity secondary to an intraventricular hemorrhage or as part of a multicompartment bleed in cases of traumatic subdural hemorrhages are eligible 4. Need for ongoing oral anticoagulant therapy for indication other than AF (e.g. mechanical heart valve, venous thromboembolic disease) 5. Need for ongoing antiplatelet therapy for indication where edoxaban would not be a suitable substitute 6. Plans for left atrial appendage occlusion 7. Estimated creatinine clearance (CrCl) < 15 mL/min 8. Platelet count less than 100,000mm3 at enrollment or other bleeding diathesis 9. Persistent, uncontrolled hypertension (systolic BP averaging >150 mmHg) 10. Chronic use of NSAID 11. Clinically significant active bleeding, including gastrointestinal bleeding 12. Lesions or conditions at increased risk of clinically significant bleeding, e.g. active peptic ulcer disease with recent bleeding, patients with spontaneous or acquired impairment of hemostasis 13. Antiphospholipid antibody syndrome 14. Hepatic disease associated with coagulopathy and clinically relevant bleeding risk 15. Known hypersensitivity to edoxaban 16. Estimated inability to adhere to study procedures 17. Pregnancy or breastfeeding 18. Estimated life expectancy < 6 months at the time of enrollment 19. Close affiliation with the investigational site; e.g. a close relative for the investigator, dependent person (e.g., employee or student of the investigational site) 20. Lobar intraparenchymal hemorrhage - Post menopausal female subjects must be amenorrheic for ≥12 months prior to screening or ≥6 weeks post-surgical bilateral oophorectomy (with or without hysterectomy) prior to screening. Women of childbearing potential must have negative serum pregnancy test within 7 days prior to randomization or urine pregnancy testing within 24 hours of randomization. Heterosexually active women of childbearing potential must use highly effective methods of contraception for 32 days after discontinuation (duration of study drug plus 30 days duration of one ovulatory cycle).
Study Design
- Phase
- Phase 4
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Prospective, randomized, open, blinded end-point (PROBE), multicenter international trial
- Primary Purpose
- Prevention
- Masking
- Single (Outcomes Assessor)
- Masking Description
- open label study where outcomes assessor is blinded to treatment allocation
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Edoxaban 60/30mg daily |
Edoxaban 60/30 mg daily (lower dose depending on clinical criteria) |
|
|
Active Comparator Non-anticoagulant medical therapy |
Non-anticoagulant medical therapy: no antithrombotic therapy or antiplatelet monotherapy (at discretion of local investigator) |
|
Recruiting Locations
New Orleans, Louisiana 70112
More Details
- Status
- Recruiting
- Sponsor
- Population Health Research Institute
Detailed Description
The EdoxabaN foR IntraCranial Hemorrhage survivors with Atrial Fibrillation (ENRICH-AF) study is a prospective, randomized open-label, blinded end-point (PROBE), investigator-initiated, study that will define the efficacy and safety of edoxaban compared with non-anticoagulant medical therapy (no antithrombotic therapy or antiplatelet monotherapy) for stroke prevention in high-risk AF patients and previous intracranial hemorrhage. Intracranial hemorrhage includes intracerebral hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage and subdural hematoma. Recruitment will occur at 250-300 stroke research centres in North and South America, Europe and Asia over 24 months, where 1200 adult participants with high-risk AF (CHA2DS2-VASc score ≥2) and previous spontaneous or traumatic intracranial hemorrhage (while on or off antithrombotic therapy) will be randomly assigned to receive edoxaban 60/30 mg daily or to non-anticoagulant medical therapy (no antithrombotic therapy or antiplatelet monotherapy). Consenting participants will be followed to a common study end-date in this event-driven trial once 123 primary efficacy events (stroke) have accrued; anticipated to be about 12 months after the end of recruitment. ENRICH-AF will assess the safety and efficacy of anticoagulant therapy in AF participants after intracranial hemorrhage, an area where there currently exists huge interest within the stroke and cardiology research communities. Demonstrating safety comparable with non-anticoagulant medical therapy in AF patients who are particularly at high risk for intracranial hemorrhage is likely to have a more far-reaching clinical impact than solely within the proposed study population. ENRICH-AF will be the "ultimate safety test" of anticoagulation of AF patients, providing reassuring evidence favoring more widespread use of anticoagulation for stroke prevention in AF patients.