MENA Regional Endovascular Intervention for Venous Cerebral Venous Sinus Thrombosis

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.

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