EdoxabaN for IntraCranial Hemorrhage Survivors with Atrial Fibrillation (ENRICH-AF)
- Conditions
- Intracranial HemorrhagesAtrial Fibrillation
- Interventions
- Other: Non-anticoagulant medical therapy
- Registration Number
- NCT03950076
- Lead Sponsor
- Population Health Research Institute
- Brief Summary
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) or systemic embolism in high-risk atrial fibrillation (CHA2DS2-VASc ≥2) patients with previous intracranial hemorrhage.
- 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/systemic embolism 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 948
- Written informed consent provided
- Age ≥45 years, at the time of signing the informed consent
- 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
- Documented atrial fibrillation (paroxysmal, persistent, permanent)
- CHA2DS2-VASc score ≥2
-
Recent intracranial hemorrhage (within 14 days)
-
Secondary macrovascular, neoplastic or infectious causes of intracranial hemorrhage (except for antithrombotic treatment or non-penetrating traumatic subdural hemorrhages)
-
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
-
Need for ongoing oral anticoagulant therapy for indication other than AF (e.g. mechanical heart valve, venous thromboembolic disease)
-
Need for ongoing antiplatelet therapy for indication where edoxaban would not be a suitable substitute
-
Plans for left atrial appendage occlusion
-
Estimated creatinine clearance (CrCl) < 15 mL/min
-
Platelet count less than 100,000mm3 at enrollment or other bleeding diathesis
-
Persistent, uncontrolled hypertension (systolic BP averaging >150 mmHg)
-
Chronic use of NSAID
-
Clinically significant active bleeding, including gastrointestinal bleeding
-
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
-
Antiphospholipid antibody syndrome
-
Hepatic disease associated with coagulopathy and clinically relevant bleeding risk
-
Known hypersensitivity to edoxaban
-
Estimated inability to adhere to study procedures
-
Pregnancy or breastfeeding
-
Estimated life expectancy < 6 months at the time of enrollment
-
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)
-
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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Non-anticoagulant medical therapy Non-anticoagulant medical therapy Non-anticoagulant medical therapy: no antithrombotic therapy or antiplatelet monotherapy (at discretion of local investigator) Edoxaban 60/30mg daily Edoxaban Edoxaban 60/30 mg daily (lower dose depending on clinical criteria)
- Primary Outcome Measures
Name Time Method Stroke or Systemic Embolism From randomization until the common study end date (average of 3 years) Stroke (composite of ischemic, hemorrhagic and unspecified) or systemic embolism
Major hemorrhage From randomization until the common study end date (median 2 years) as defined byt the International Society on Thrombosis and Haemostasis (ISTH) criteria
- Secondary Outcome Measures
Name Time Method Ischemic stroke From randomization until the common study end date (median 2 years) development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute ischemic stroke.
Cardiovascular death From randomization until the common study end date (median 2 years) Death related to cardiovascular cause
Hemorrhagic stroke From randomization until the common study end date (median 2 years) development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute intraparenchymal, intraventricular or subarachnoid hemorrhage
All intracranial hemorrhage (intracerebral hemorrhage, intraventricular hemorrhage, subdural hematoma, subarachnoid hemorrhage) From randomization until the common study end date (median 2 years) Intracranial hemorrhage as defined by Signs or symptoms associated with an epidural, subdural, subarachnoid, intraparenchymal or intraventricular hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy.
Net clinical benefit (composite of stroke, myocardial infarction, cardiovascular death, fatal bleeding, and symptomatic bleeding into a critical organ or area) From randomization until the common study end date (median 2 years) Net clinical benefit is a composite of stroke, myocardial infarction, cardiovascular death, fatal bleeding, and symptomatic bleeding into a critical organ or area
Composite of all stroke, myocardial infarction, systemic thromboembolism, or all-cause death From randomization until the common study end date (median 2 years) Components of composite outcome (adjudicated) includes stroke (ischemic, hemorrhagic, and undefined stroke, TIA with positive neuroimaging),myocardial infarction, systemic thromboembolism or all-cause death. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred
Fatal intracranial hemorrhage From randomization until the common study end date (median 2 years) Inctracranial hemorrhage defined as Signs or symptoms associated with an epidural, subdural, subarachnoid, intraparenchymal or intraventricular hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy with death occurring within 30 days of stroke
Subdural hemorrhage From randomization until the common study end date (median 2 years) Subdural hemorrhage as defined as Signs or symptoms associated with a subdural hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy
Hospitalization for any cause From randomization until the common study end date (median 2 years) Minimum of one overnight stay in hospital.
Disabling/fatal stroke From randomization until the common study end date (median 2 years) Disabling stroke is defined as stroke resulting in a clinical outcome that is associated with a modified Rankin scale of 4 or 5. Fatal stroke is defined as death occurring within 30 days of stroke.
modified Rankin Scale 12 months mRS as measured at 12 month visit
Trial Locations
- Locations (152)
Alexian Brothers Medical Center
🇺🇸Elk Grove Village, Illinois, United States
Presence Care Transformation Corporation
🇺🇸Lisle, Illinois, United States
Tulane University Medical Center
🇺🇸New Orleans, Louisiana, United States
New York Presbyterian - Queens
🇺🇸Queens, New York, United States
The Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
The University of Texas at Austin, Dell Medical School
🇺🇸Austin, Texas, United States
Texas Tech University Health Sciences Center at El Paso
🇺🇸El Paso, Texas, United States
Baylor St. Luke's Medical Center
🇺🇸Houston, Texas, United States
MultiCare Institute for Research & Innovation
🇺🇸Tacoma, Washington, United States
Scroll for more (142 remaining)Alexian Brothers Medical Center🇺🇸Elk Grove Village, Illinois, United States