EdoxabaN foR IntraCranial Hemorrhage Survivors With Atrial Fibrillation (ENRICH-AF)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 948
- 试验地点
- 152
- 主要终点
- Stroke or Systemic Embolism
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
open label study where outcomes assessor is blinded to treatment allocation
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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).
研究组 & 干预措施
Edoxaban 60/30mg daily
Edoxaban 60/30 mg daily (lower dose depending on clinical criteria)
干预措施: Edoxaban (Drug)
Non-anticoagulant medical therapy
Non-anticoagulant medical therapy: no antithrombotic therapy or antiplatelet monotherapy (at discretion of local investigator)
干预措施: Non-anticoagulant medical therapy (Other)
结局指标
主要结局
Stroke or Systemic Embolism
时间窗: From randomization until the common study end date (average of 3 years)
Stroke (composite of ischemic, hemorrhagic and unspecified) or systemic embolism
Major hemorrhage
时间窗: From randomization until the common study end date (median 2 years)
as defined byt the International Society on Thrombosis and Haemostasis (ISTH) criteria
次要结局
- Ischemic stroke(From randomization until the common study end date (median 2 years))
- Cardiovascular death(From randomization until the common study end date (median 2 years))
- Hemorrhagic stroke(From randomization until the common study end date (median 2 years))
- All intracranial hemorrhage (intracerebral hemorrhage, intraventricular hemorrhage, subdural hematoma, subarachnoid hemorrhage)(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)(From randomization until the common study end date (median 2 years))
- Hospitalization for any cause(From randomization until the common study end date (median 2 years))
- Composite of all stroke, myocardial infarction, systemic thromboembolism, or all-cause death(From randomization until the common study end date (median 2 years))
- modified Rankin Scale(12 months)
- Fatal intracranial hemorrhage(From randomization until the common study end date (median 2 years))
- Subdural hemorrhage(From randomization until the common study end date (median 2 years))
- Disabling/fatal stroke(From randomization until the common study end date (median 2 years))