REVIVE-CVST: A Multicenter, Prospective, Randomized, Open-Label, Blinded-Endpoint (PROBE) Trial of Endovascular Thrombectomy Plus Standard Medical Care Versus Standard Medical Care Alone in Adults With Acute or Subacute Cerebral Venous Sinus Thrombosis at High Risk of Poor Outcome in the Middle East and North Africa Region
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 440
- 试验地点
- 14
- 主要终点
- Proportion of patients achieving functional independence (mRS 0-2) at 12 months
研究概览
简要总结
REVIVE-CVST is a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) trial evaluating whether early endovascular thrombectomy (EVT) combined with standard anticoagulation improves outcomes compared to anticoagulation alone in patients with severe cerebral venous sinus thrombosis (CVST).
The study targets adult patients (aged 18 years or older) presenting within 14 days of symptom onset with imaging-confirmed CVST and at least one severity marker, such as a Glasgow Coma Scale score of 14 or below, intracerebral hemorrhage, venous infarction, or deep venous system involvement.
Participants will be randomly assigned in a 1:1 ratio to either the intervention arm (EVT plus anticoagulation) or the control arm (anticoagulation alone). The primary endpoint is functional outcome at 180 days as measured by the modified Rankin Scale (mRS), using a shift analysis across all mRS categories.
The trial aims to enroll 440 participants across approximately 15 centers in the Middle East, North Africa, South Asia, and Turkey (MENA-SINO network). The study duration is approximately 42 months, including 18 months of enrollment and 12 months of follow-up for the last enrolled patient.
详细描述
BACKGROUND: Cerebral venous sinus thrombosis (CVST) accounts for approximately 0.5-1% of all strokes and disproportionately affects younger patients, particularly women. While anticoagulation remains the standard of care, approximately 15% of patients experience poor outcomes despite treatment. Endovascular thrombectomy (EVT) has emerged as a potential adjunctive therapy for severe CVST, but high-quality evidence from randomized controlled trials is lacking, particularly from the Middle East, North Africa, and South Asia regions where CVST prevalence may be higher.
STUDY DESIGN: This is a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) trial. Participants are randomized 1:1 to either EVT plus anticoagulation (intervention) or anticoagulation alone (control). Randomization is stratified by site and presence of intracerebral hemorrhage.
INTERVENTION ARM: Patients receive endovascular thrombectomy using mechanical thrombectomy devices, aspiration catheters, or balloon-assisted techniques, performed within 24 hours of randomization. All patients also receive standard anticoagulation therapy.
CONTROL ARM: Patients receive standard anticoagulation therapy alone, consisting of intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin, followed by oral anticoagulation for 3-12 months per guidelines.
FOLLOW-UP: Assessments are conducted at 30 days, 90 days, and 180 days post-randomization. The primary endpoint assessment occurs at 180 days. Follow-up includes clinical assessments (mRS, NIHSS), quality of life measures (EQ-5D-5L), and imaging at 90 days.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65 years, inclusive
- •Radiologically confirmed cerebral venous sinus thrombosis (CVST) by CT venography (CTV), MR venography (MRV), or digital subtraction angiography (DSA), with thrombosis of at least one major dural sinus
- •Acute or subacute presentation with symptom onset within 21 days of randomization
- •MRI phase characterization confirming acute or subacute phase
- •At least one risk factor for poor outcome: symptoms of intracranial hypertension (severe headache, papilledema, visual obscurations), focal neurological deficit, seizures, altered consciousness (GCS 9-14), intracranial hemorrhage from venous congestion, or deep venous system thrombosis
- •Significant venous outflow obstruction on imaging
- •Written informed consent from patient or legally authorized representative
排除标准
- •Isolated cortical vein thrombosis without dural sinus involvement
- •Isolated cavernous sinus thrombosis
- •Chronic-phase CVST on MRI phase characterization
- •Pre-morbid modified Rankin Scale (mRS) score greater than 2
- •Glasgow Coma Scale (GCS) score less than 9 at randomization
- •Imminent risk of transtentorial herniation requiring emergent decompressive craniectomy
- •Massive cerebral edema with midline shift greater than 10 mm requiring surgical intervention
- •Active systemic bleeding or hemorrhagic diathesis
- •Severe allergy to iodinated contrast media
- •CVST secondary to active hematological malignancy or life expectancy less than 12 months
- •Pregnancy
- •Participation in another interventional clinical trial within 30 days
- •Any condition rendering the patient unsuitable for study participation per investigator judgment
研究组 & 干预措施
Anticoagulation Alone
Participants in this arm will receive standard anticoagulation therapy alone. Treatment consists of intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin during the acute phase, followed by oral anticoagulation (warfarin or direct oral anticoagulants) for 3-12 months as per current guidelines. No endovascular intervention will be performed.
干预措施: Anticoagulation Therapy (Drug)
Endovascular Thrombectomy Plus Anticoagulation
Participants in this arm will receive endovascular thrombectomy (EVT) within 24 hours of randomization, in addition to standard anticoagulation therapy. EVT techniques may include mechanical thrombectomy, aspiration thrombectomy, or balloon-assisted techniques at the discretion of the treating interventionalist. Standard anticoagulation consists of intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin, followed by oral anticoagulation for 3-12 months per guidelines.
干预措施: Endovascular Thrombectomy (Procedure)
Endovascular Thrombectomy Plus Anticoagulation
Participants in this arm will receive endovascular thrombectomy (EVT) within 24 hours of randomization, in addition to standard anticoagulation therapy. EVT techniques may include mechanical thrombectomy, aspiration thrombectomy, or balloon-assisted techniques at the discretion of the treating interventionalist. Standard anticoagulation consists of intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin, followed by oral anticoagulation for 3-12 months per guidelines.
干预措施: Anticoagulation Therapy (Drug)
结局指标
主要结局
Proportion of patients achieving functional independence (mRS 0-2) at 12 months
时间窗: 12 months after randomization
The primary efficacy endpoint is the proportion of patients achieving a modified Rankin Scale (mRS) score of 0-2 at 12 months after randomization, assessed by a blinded central adjudication committee. The mRS is a 7-point disability scale ranging from 0 (no symptoms) to 6 (death). A score of 0-2 indicates functional independence.
次要结局
- Venous sinus recanalization rate at Day 7(7 days after randomization)
- Modified Rankin Scale (mRS) ordinal shift analysis(6 and 12 months after randomization)
- All-cause mortality(30 days and 12 months after randomization)
- Time to clinical improvement(Up to 12 months after randomization)
- Health-related quality of life (EQ-5D-5L)(6 and 12 months after randomization)
- Cognitive function (Montreal Cognitive Assessment)(6 and 12 months after randomization)
- Seizure frequency(Up to 12 months after randomization)
研究者
Ossama Mansour
Professor of Neurology, Alexandria University
Alexandria University