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EdoxabaN foR IntraCranial Hemorrhage Survivors With Atrial Fibrillation (ENRICH-AF) (ENRICH-AF)

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ClinicalTrials.gov Identifier: NCT03950076
Recruitment Status : Recruiting
First Posted : May 15, 2019
Last Update Posted : October 29, 2019
Sponsor:
Information provided by (Responsible Party):
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) in high-risk atrial fibrillation (CHA2DS2-VASc ≥2) patients with previous intracranial hemorrhage.

Condition or disease Intervention/treatment Phase
Intracranial Hemorrhages Atrial Fibrillation Drug: Edoxaban Other: Non-anticoagulant medical therapy Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective, randomized, open, blinded end-point (PROBE), multicenter international trial
Masking: Single (Outcomes Assessor)
Masking Description: open label study where outcomes assessor is blinded to treatment allocation
Primary Purpose: Prevention
Official Title: EdoxabaN foR IntraCranial Hemorrhage Survivors With Atrial Fibrillation (ENRICH-AF)
Actual Study Start Date : September 20, 2019
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Edoxaban

Arm Intervention/treatment
Experimental: Edoxaban 60/30mg daily
Edoxaban 60/30 mg daily (lower dose depending on clinical criteria)
Drug: Edoxaban
Edoxaban 60mg (or 30mg as determined by clinical criteria)
Other Names:
  • Lixana
  • Savaysa

Active Comparator: Non-anticoagulant medical therapy
Non-anticoagulant medical therapy: no antithrombotic therapy or antiplatelet monotherapy (at discretion of local investigator)
Other: Non-anticoagulant medical therapy
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




Primary Outcome Measures :
  1. Stroke [ Time Frame: From randomization until the common study end date (median 2 years) ]
    composite of ischemic, hemorrhagic and unspecified

  2. Major hemorrhage [ Time Frame: 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 :
  1. Ischemic stroke [ Time Frame: 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.

  2. cardiovascular death [ Time Frame: From randomization until the common study end date (median 2 years) ]
    Death related to cardiovascular cause

  3. hemorrhagic stroke [ Time Frame: 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

  4. Disabling/fatal stroke [ Time Frame: 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.

  5. composite of all stroke, myocardial infarction, systemic thromboembolism, or all-cause death [ Time Frame: 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

  6. net clinical benefit (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) ]
    Net clinical benefit is a composite of stroke, myocardial infarction, cardiovascular death, fatal bleeding, and symptomatic bleeding into a critical organ or area

  7. modified Rankin Scale [ Time Frame: 12 months ]
    mRS as measured at 12 month visit

  8. All intracranial hemorrhage (intracerebral hemorrhage, intraventricular hemorrhage, subdural hematoma, subarachnoid hemorrhage) [ Time Frame: 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.

  9. Fatal intracranial hemorrhage [ Time Frame: 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

  10. Subdural hemorrhage [ Time Frame: 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

  11. Hospitalization for any cause [ Time Frame: From randomization until the common study end date (median 2 years) ]
    Minimum of one overnight stay in hospital.



Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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 intraparenchymal, intraventricular, and/or cSAH, and symptomatic spontaneous or non-penetrating traumatic subdural hemorrhages) on or off antithrombotic therapy, and confirmed to have stabilized on neuroimaging.
  4. Documented atrial fibrillation (paroxysmal, persistent, permanent)
  5. CHA2DS2-VASc score ≥2

Exclusion Criteria:

  1. 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. Traumatic or aneurysmal cSAH
  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 or other creatinine clearance following local product monograph (Canada < 30mL/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)

    • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03950076


Contacts
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Contact: Amanda Taylor 905-527-4322 ext 40508 ENRICH-AF@phri.ca
Contact: Ellison Themeles 905-527-4322 ext 40488 ENRICH-AF@phri.ca

Locations
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Canada, Ontario
Hamilton Health Sciences Recruiting
Hamilton, Ontario, Canada, L8L2X2
Contact: Luciana Catanese       Luciana.Catanese@PHRI.CA   
Sponsors and Collaborators
Population Health Research Institute
Investigators
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Principal Investigator: Ashkan Shoamanesh, MD. FRCPC Population Health Research Institute
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Responsible Party: Population Health Research Institute
ClinicalTrials.gov Identifier: NCT03950076    
Other Study ID Numbers: ENRICH-AF
First Posted: May 15, 2019    Key Record Dates
Last Update Posted: October 29, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Population Health Research Institute:
Edoxaban
Intracranial Hemorrhage
Hemorrhagic Stroke
Additional relevant MeSH terms:
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Intracranial Hemorrhages
Atrial Fibrillation
Hemorrhage
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Edoxaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants