Rivaroxaban Versus Warfarin in Acute Ischemic Stroke With Atrial Fibrillation: Acute Stroke With Xarelto to Reduce Intracranial Bleeding, Recurrent Embolic Stroke, and Hospital Stay, Phase 2, Conceptual Multicenter Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 195
- 试验地点
- 1
- 主要终点
- Number of Participants With Intracranial Bleeding and/or Recurrent Ischemic Lesion as Confirmed by MRI Imaging
研究概览
简要总结
Rationale Acute ischemic stroke due to atrial fibrillation (AF) carries a high risk for early recurrence. In acute stage, guidelines recommend aspirin, but do not recommend anticoagulation due to the increased risk of intracranial bleeding. Since, aspirin has a limited efficacy of preventing recurrent stroke in AF, expert consensus suggests early anticoagulation in non-severe stroke with AF. The current practice for acute ischemic stroke patients with AF is delayed warfarin administration with aspirin use for non-minor stroke or immediate warfarin administration (sometimes with heparin bridging) for minor stroke. However, conventional anticoagulation with warfarin in acute ischemic stroke with AF has the following limitations: 1) risk of intracranial bleeding particularly in acute stage, 2) delayed action and transient paradoxical thrombogenic tendency due to the inhibition of protein C, resulting in the risk of early recurrent embolic stroke, and 3) prolongation of hospitalization waiting for full anticoagulation. In contrast, as compared to warfarin, rivaroxaban is advantageous for reduced risk of intracranial bleeding and immediate anticoagulation efficacy.
Goal The current trial will examine whether early initiation (within 5 days from stroke onset) of rivaroxaban as compared to conventional warfarin would reduce intracranial bleeding, recurrent embolic stroke, and hospital stay in patients with acute ischemic stroke due to AF.
详细描述
Primary endpoint: Composite of MRI-defined intracranial bleeding and recurrent ischemic lesion within 1 month after randomization (rivaroxaban vs conventional warfarin)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All of below
- •Acute ischemic stroke or TIA presumed to be cardioembolic origin (within 5 days from stroke onset) with mild severity: infarct size on DWI less than 1/3 of MCA territory, 1/2 of ACA territory, 1/2 of PCA territory, and 1/2 of one cerebellar hemisphere
- •Atrial fibrillation including paroxysmal atrial fibrillation: atrial fibrillation must be documented by ECG evidence (e.g., 12-lead ECG, rhythm strip, Holter, pacemaker interrogation) within 30 days before randomization. This could be obtained from a notation in the subject's record (e.g., medical chart, hospital discharge summary).
- •Age ≥19 years
- •Informed consent
排除标准
- •Any of below
- •Chronic renal failure (GFR less than 30ml/min) or severe hepatic impairment
- •Significant hemorrhagic transformation (parenchymal hematoma type I or II by the ECASS definition)
- •Stroke mechanism of presumed small vessel occlusion: single small subcortical infarct in the perforating artery territory
- •Large hemispheric or cerebellar infarction; larger than 1/3 of MCA territory, 1/2 of ACA territory, 1/2 of PCA territory, and 1/2 of one cerebellar hemisphere
- •Mechanical valve requiring warfarin therapy
- •Active internal bleeding
- •Prior history of symptomatic intracranial bleeding
- •: patients with asymptomatic bleedings or microbleedings on MRI are eligible for inclusion
- •Major surgery or major trauma within 30 days that might be associated with increased bleeding risk
- •Clinically significant gastrointestinal bleeding within 6 months
- •Intravenous tissue plasminogen activator use or mechanical embolectomy within 48 hours plus 'significant hemorrhagic transformation as described above (exclusion criteria 2)' or 'large hemispheric infarction or cerebellar infarction as described above (exclusion criteria 4)'
- •: patients achieving successful reperfusion without hemorrhage nor large infarction are eligible for enrollment
- •Severe anemia: hemoglobin <10 g/dL
- •Bleeding diathesis; thrombocytopenia (<90,000/µL, prolonged PT (INR>1.7)
- •Sustained uncontrolled hypertension: SBP >180 mmHg or DBP >100 mmHg
- •Severe devastating illness, such terminal cancer, hepatic failure; therefore, the participants have a life expectancy less than 6 months.
- •Planned invasive procedure with potential for uncontrolled bleeding, including major surgery
研究组 & 干预措施
Rivaroxaban
Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days.
干预措施: Rivaroxaban (Drug)
Warfarin
Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 [2.0 - 3.0].
干预措施: Warfarin (Drug)
结局指标
主要结局
Number of Participants With Intracranial Bleeding and/or Recurrent Ischemic Lesion as Confirmed by MRI Imaging
时间窗: 1 month after randomization
Intracranial bleeding: symptomatic hemorrhage confirmed by CT or MRI or asymptomatic hemorrhage on follow-up GRE or SWI imaging at 1 month Recurrent ischemic lesion: symptomatic ischemic stroke confirmed by relevant neuroimagings or asymptomatic recurrent ischemic lesion on follow-up or FLAIR imaging at 1 month
次要结局
- The Number of Patients With Intracranial Bleeding(at 1 month)
- Number of Participants With Modified Rankin Score of 0 or 1 at Week 4(at 1 month)
- Length of Hospitalization(at 1month)
- The Number of Patients With Recurrent Ischemic Lesion(at 1 month)
研究者
Sun U. Kwon
Professor
Asan Medical Center