Apixaban Versus Dual-antiplatelet Therapy (Clopidogrel and Aspirin) in High-risk Patients With Acute Non-disabling Cerebrovascular Events (ADANCE): Rationale, Objectives, and Design
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 10,000
- 试验地点
- 1
- 主要终点
- percentage of patients with new stroke (ischemic or hemorrhage)
研究概览
简要总结
Nondisabling cerebrovascular events represent the largest group of cerebrovascular disease with a high risk of recurrent stroke. A recent trial indicated that clopidogrel and aspirin treatment reduced the risk of recurrent stroke and was not associated with increased hemorrhage events, compared with aspirin monotherapy. Apixaban, a new oral anticoagulant, is proved to be as effective as traditional anticoagulants with less risk of bleeding events.
To estimate whether apixaban is beneficial for acute TIA or minor stroke, a randomized, double-blind, multicenter, controlled clinical trial has been designed. The investigators will assess the hypothesis that a 21-days apixaban regimen is superior to clopidogrel and aspirin dual-therapy for the treatment of high-risk patients with acute nondisabling cerebrovascular event.
详细描述
The ADANCE study is a randomized, double-blind clinical trial with a target enrollment of 3,000 Chinese patients. Two subtypes of patients will be enrolled: I, acute disabling ischemic stroke (<24 hours of symptoms onset); II, acute TIA (<24 hours of symptoms onset).
Patients will be randomized into 3 groups:
Ⅰ Receiving a 75 mg dose of clopidogrel and 75mg dose of aspirin from day 1 to day 21, with placebo apixaban twice daily.
Ⅱ Receiving a 2.5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21.
Ⅲ Receiving a 5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult subjects (male or female ≥18 years old)
- •Acute nondisabling ischemic stroke (NIHSS ≤3 at the time of randomization) that can be treated with study drug within 24 hours of symptoms onset. Symptom onset is defined by the "last see normal" principle
- •TIA (neurologic deficit attributed to focal brain ischemia, with resolution of the deficit within 24 hours of symptom onset), that can be treated with investigational medication within 24 hours of symptoms onset. Symptom onset is defined by the "last see normal" principle
- •Informed consent signed
排除标准
- •Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other major nonischemic brain disease, on baseline head CT or MRI scan
- •mRS score >2 at randomization (premorbid historical assessment) NIHSS ≥4 at randomization
- •Clear indication for anticoagulation (atrial fibrillation, mechanical cardiac valves, deep venous thrombosis, pulmonary embolism or known hypercoagulable state)
- •Contraindication to investigational medications
- •Thrombolysis for ischemic stroke within preceding 7 days
- •History of intracranial hemorrhage
- •Current treatment (last dose given within 10 days before randomization) with heparin therapy or oral anticoagulation
- •Gastrointestinal bleed or major surgery within 3 months
- •Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months
- •TIA or minor stroke induced by angiography or surgery
- •Severe noncardiovascular comorbidity with life expectancy <3 months
- •Women of childbearing age not practicing reliable contraception who do not have a documented negative pregnancy test result
- •Severe renal failure, defined as Glomerular Filtration Rate (GFR) <30 ml/min Severe hepatic insufficiency (Child-Pugh score B to C)
研究组 & 干预措施
Dual-antiplatelet Therapy
Receiving a 75 mg dose of clopidogrel and 75mg dose of aspirin from day 1 to day 21, with placebo apixaban twice daily
干预措施: Clopidogrel (Drug)
Dual-antiplatelet Therapy
Receiving a 75 mg dose of clopidogrel and 75mg dose of aspirin from day 1 to day 21, with placebo apixaban twice daily
干预措施: Aspirin (Drug)
Dual-antiplatelet Therapy
Receiving a 75 mg dose of clopidogrel and 75mg dose of aspirin from day 1 to day 21, with placebo apixaban twice daily
干预措施: placebo (Drug)
Apixaban 2.5mg
Receiving a 2.5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21
干预措施: Apixaban (Drug)
Apixaban 2.5mg
Receiving a 2.5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21
干预措施: placebo (Drug)
Apixaban 5mg
Receiving a 5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21
干预措施: Apixaban (Drug)
Apixaban 5mg
Receiving a 5-mg twice daily of apixaban, with placebo clopidogrel and placebo aspirin from day 1 to day 21
干预措施: placebo (Drug)
结局指标
主要结局
percentage of patients with new stroke (ischemic or hemorrhage)
时间窗: 90 days
次要结局
- Changes in NIHSS scores(90 days)
- Percentage of patients with new clinical vascular events (ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death)(30 days and 90 days)
- Adverse events/severe adverse events reported by the investigators(90 days)
- moderate to severe bleeding events(90 days)
- Total mortality(90 days)