Cerebral Venous Sinus Thrombosis
Conditions
Keywords
CVST, endovascular thrombectomy, anticoagulation
Brief summary
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.
Detailed description
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.
Interventions
PROCEDUREEndovascular Thrombectomy
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.
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.
Sponsors
Middle East North Africa Stroke and Interventional Neurotherapies Organization
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients achieving functional independence (mRS 0-2) at 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Venous sinus recanalization rate at Day 7 | 7 days after randomization | 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. |
| Modified Rankin Scale (mRS) ordinal shift analysis | 6 and 12 months after randomization | 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). |
| All-cause mortality | 30 days and 12 months after randomization | All-cause mortality at 30 days and 12 months after randomization. |
| Time to clinical improvement | Up to 12 months after randomization | 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. |
| Health-related quality of life (EQ-5D-5L) | 6 and 12 months after randomization | 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. |
| Cognitive function (Montreal Cognitive Assessment) | 6 and 12 months after randomization | 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. |
| Seizure frequency | Up to 12 months after randomization | Frequency and type of seizures (focal or generalized) occurring during the follow-up period, documented at each study visit. |
Countries
Egypt, Jordan, Morocco, Pakistan, Qatar, Saudi Arabia, Tunisia, Turkey (Türkiye)
Outcome results
None listed