High risk atrial fibrillation patients with previous intracranial hemorrhage MedDRA version: 21.1 Level: PT Classification code 10018985 Term: Haemorrhage intracranial System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: PT Classification code 10003658 Term: Atrial fibrillation System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: Lixiana
Product Name: Edoxaban
Pharmaceutical Form: Film-coated tablet
Trade Name: Lixiana
Product Name: Edoxaban
Pharmaceutical Form: Film-coated tablet
Sponsors
Hamilton Health Sciences, through its Population Health Research Institute
Eligibility
Sex/Gender
All
Inclusion 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 (Table 2) 4. Documented atrial fibrillation (paroxysmal, persistent, permanent) 5. CHA2DS2-VASc score =2 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 240 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 960
Exclusion criteria
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) 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether edoxaban (60/30 mg daily) compared to non-anticoagulant 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 score =2) patients with previous intracranial hemorrhage.;Secondary Objective: i) To assess whether edoxaban (60/30 mg daily) compared to non-anticoagulant medical therapy (either no antithrombotic therapy or antiplatelet monotherapy) reduces the risk of cardiovascular death in high-risk atrial fibrillation participants with previous intracranial hemorrhage. ii) To assess whether edoxaban (60/30 mg daily) is associated with increased risk of major hemorrhage compared to standard of care (either no antithrombotic therapy or antiplatelet monotherapy). ;Primary end point(s): The primary efficacy end point is stroke (composite of ischemic, hemorrhagic and unspecified). The primary safety endpoint is major hemorrhage as defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria ;Timepoint(s) of evaluation of this end point: Participants will be followed every 6 months until the common study end date. This trial is event driven to accrue 123 primary events, anticipated one year after the end of the recruitment. Follow up is anticipated to be an average of 24 months per participant (range 1 to 3 years). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy end points are: 1. Ischemic stroke 2. Cardiovascular death 3. Hemorrhagic stroke 4. Disabling/fatal stroke 5. Composite of all stroke, myocardial infarction, systemic thromboembolism or all-cause death 6. Net clinical benefit (composite of stroke, myocardial infarction, cardiovascular death, fatal bleeding, and symptomatic bleeding into a critical organ or area) 7. Modified Rankin scale (mRS) at 12 months The secondary safety end point(s) are: 1. All intracranial hemorrhage (intracerebral hemorrhage, intraventricular hemorrhage, subdural hematoma, subarachnoid hemorrhage) 2. Fatal intracranial hemorrhage 3. Subdural hemorrhage 4. Hospitalization for any cause ;Timepoint(s) of evaluation of this end point: Timepoints of evaluation will be every 6 months until the common study end date. Follow up is anticipated to be an average of 24 months per participant (range 1 to 3 years). | — |
Countries
Argentina, Austria, Belgium, Canada, Chile, China, Czech Republic, Egypt, Germany, Greece, India, Italy, Korea, Republic of, Nepal, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Switzerland, Taiwan, United Kingdom
Contacts
Public ContactENRICH-AF Research Coordinator
Hamilton Health Sciences, through its Population Health Research Institute
Outcome results
None listed