Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
STATISTICAL ANALYSIS: The primary analysis uses ordinal logistic regression (shift analysis) of the mRS at 180 days. The study is powered at 80% to detect a common odds ratio of 1.5 with a two-sided alpha of 0.05, requiring 440 participants (220 per arm) including a 10% attrition allowance.
SAFETY: An independent Data Safety Monitoring Board (DSMB) will conduct interim analyses after enrollment of 25%, 50%, and 75% of participants. Pre-specified stopping rules are based on the Haybittle-Peto boundary.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Endovascular Thrombectomy Plus Anticoagulation | Experimental | 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. |
|
| Anticoagulation Alone | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Endovascular Thrombectomy | Procedure | Endovascular thrombectomy (EVT) performed within 24 hours of randomization. Techniques include mechanical thrombectomy using stent retrievers, aspiration thrombectomy, balloon-assisted thrombectomy, or a combination approach at the discretion of the treating neurointerventionalist. The procedure is performed under general anesthesia or conscious sedation via femoral venous access with navigation to the affected cerebral venous sinus. |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of patients achieving functional independence (mRS 0-2) at 12 months | 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. | 12 months after randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Venous sinus recanalization rate at Day 7 | Proportion of patients achieving partial or complete recanalization of the affected venous sinuses at Day 7, assessed by CT venography (CTV) or MR venography (MRV). Recanalization is graded as no recanalization, partial recanalization, or complete recanalization by a blinded central imaging core lab. | 7 days after randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Safety composite: sICH and major procedural complications (co-primary safety endpoint) | Co-primary safety endpoint comprising: (1) symptomatic intracranial hemorrhage (sICH) within 72 hours, defined as new or worsening hemorrhage on imaging with clinical deterioration (increase of 4 or more points on NIHSS); and (2) major procedural complications within 30 days, including vessel perforation, dissection, or device-related events requiring intervention. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alexandria University, Smouha Comprehensive Stroke Center | Alexandria | Egypt |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Anticoagulation Therapy | Drug | Standard anticoagulation therapy consisting of intravenous unfractionated heparin (UFH) or subcutaneous low-molecular-weight heparin (LMWH) during the acute phase, followed by oral anticoagulation with warfarin (target INR 2.0-3.0) or direct oral anticoagulants (DOACs) for 3-12 months as per current AHA/ASA and ESO guidelines. Both arms receive this intervention. |
|
| Modified Rankin Scale (mRS) ordinal shift analysis | Ordinal shift analysis of the full modified Rankin Scale (mRS) distribution at 6 and 12 months, comparing the distribution of scores between the two treatment arms using ordinal logistic regression. The mRS ranges from 0 (no symptoms) to 6 (death). | 6 and 12 months after randomization |
| All-cause mortality | All-cause mortality at 30 days and 12 months after randomization. | 30 days and 12 months after randomization |
| Time to clinical improvement | Time from randomization to clinical improvement, defined as a reduction of 2 or more points on the National Institutes of Health Stroke Scale (NIHSS) or discharge from hospital, whichever occurs first. | Up to 12 months after randomization |
| Health-related quality of life (EQ-5D-5L) | Health-related quality of life assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) instrument at 6 and 12 months after randomization. The EQ-5D-5L measures health across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. | 6 and 12 months after randomization |
| Cognitive function (Montreal Cognitive Assessment) | Cognitive function assessed using the Montreal Cognitive Assessment (MoCA) at 6 and 12 months after randomization. The MoCA is a 30-point screening tool for mild cognitive dysfunction, with scores ranging from 0 to 30. Higher scores indicate better cognitive function; a score of 26 or above is considered normal. | 6 and 12 months after randomization |
| Seizure frequency | Frequency and type of seizures (focal or generalized) occurring during the follow-up period, documented at each study visit. | Up to 12 months after randomization |
| 72 hours (sICH) and 30 days (procedural complications) after randomization |
| Ain Shams University | Cairo | Egypt |
| Cairo University | Cairo | Egypt |
| Neurology Department, Al-Azhar University | Cairo | Egypt |
| Amman Specialized IR Center | Amman | Jordan |
| Centre Hospitalier Universitaire Ibn Sina de Rabat | Rabat | Morocco |
| Aga Khan University | Karachi | Pakistan |
| Weill Cornell Medicine-Qatar | Doha | Qatar |
| King Khalid University | Abhā | Saudi Arabia |
| King Abdulaziz Medical City | Jeddah | Saudi Arabia |
| King Abdullah Medical City | Mecca | Saudi Arabia |
| Institut National de Neurologie | Tunis | Tunisia |
| Department of Neurology, Eskisehir Osmangazi University | Eskişehir | Turkey (Türkiye) |
| Neurology Department, Dr. Lutfi Kirdar City Hospital | Istanbul | Turkey (Türkiye) |
| ID | Term |
|---|---|
| D000095062 | Anticoagulation Bridge |
| ID | Term |
|---|---|
| D000093142 | Bridge Therapy |
| D013812 | Therapeutics |
Not provided
Not provided