A Phase 4 interventional study of Edoxaban and Non-anticoagulant medical therapy in Intracranial Hemorrhages and Atrial Fibrillation, sponsored by Population Health Research Institute. Completed at 152 sites in 15 countries. Open to participants aged 45 Years and older. Per ClinicalTrials.gov, last updated 2026-09-01.
Sponsored by Population Health Research Institute · Phase 4, Interventional, and Prevention
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.
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.
199 studies on the registry are indexed under Intracranial Hemorrhages; 64 are open to participants now.
This study's enrollment of 948 is above the median of 100 across 105 interventional studies indexed under Intracranial Hemorrhages.
Browse Intracranial Hemorrhages studies →Population Health Research Institute is the lead sponsor of 114 studies on the registry; 27 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
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Exclusion Criteria:
Lobar intraparenchymal hemorrhage
Edoxaban 60/30 mg daily (lower dose depending on clinical criteria)
Drug: Edoxaban
Non-anticoagulant medical therapy: no antithrombotic therapy or antiplatelet monotherapy (at discretion of local investigator)
Other: Non-anticoagulant medical therapy
Edoxaban 60mg (or 30mg as determined by clinical criteria)
Also known as: Lixiana, Savaysa
Non-anticoagulant medical therapy as determined by the local investigator includes i) No antithrombotic therapy ii) Antiplatelet monotherapy, including de novo indication for antiplatelet monotherapy during course of the study
Stroke or Systemic Embolism
Stroke (composite of ischemic, hemorrhagic and unspecified) or systemic embolism
Time frame: From randomization until the common study end date (average of 3 years)
Major hemorrhage
as defined byt the International Society on Thrombosis and Haemostasis (ISTH) criteria
Time frame: From randomization until the common study end date (median 2 years)
Ischemic stroke
development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute ischemic stroke.
Time frame: From randomization until the common study end date (median 2 years)
Cardiovascular death
Death related to cardiovascular cause
Time frame: From randomization until the common study end date (median 2 years)
Hemorrhagic stroke
development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute intraparenchymal, intraventricular or subarachnoid hemorrhage
Time frame: From randomization until the common study end date (median 2 years)
Disabling/fatal stroke
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.
Time frame: From randomization until the common study end date (median 2 years)
Composite of all stroke, myocardial infarction, systemic thromboembolism, or all-cause death
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
Time frame: From randomization until the common study end date (median 2 years)
Net clinical benefit (composite of stroke, myocardial infarction, cardiovascular death, fatal bleeding, and symptomatic bleeding into a critical organ or area)
Net clinical benefit is a composite of stroke, myocardial infarction, cardiovascular death, fatal bleeding, and symptomatic bleeding into a critical organ or area
Time frame: From randomization until the common study end date (median 2 years)
modified Rankin Scale
mRS as measured at 12 month visit
Time frame: 12 months
All intracranial hemorrhage (intracerebral hemorrhage, intraventricular hemorrhage, subdural hematoma, subarachnoid hemorrhage)
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.
Time frame: From randomization until the common study end date (median 2 years)
Fatal intracranial hemorrhage
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
Time frame: From randomization until the common study end date (median 2 years)
Subdural hemorrhage
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
Time frame: From randomization until the common study end date (median 2 years)
Hospitalization for any cause
Minimum of one overnight stay in hospital.
Time frame: From randomization until the common study end date (median 2 years)
Showing the first 100 of 152 sites across 15 countries.
This study is completed, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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