MENA Regional Endovascular Intervention for Venous Cerebral Venous Sinus Thrombosis

Official title

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

Overview

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

• Procedure Endovascular 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.
• Drug Anticoagulation Therapy
  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.

Primary outcome measures

• Proportion of patients achieving functional independence (mRS 0-2) at 12 months [Time frame: 12 months after randomization]

Secondary outcome measures (7)

• Venous sinus recanalization rate at Day 7 [Time frame: 7 days after randomization]
• Modified Rankin Scale (mRS) ordinal shift analysis [Time frame: 6 and 12 months after randomization]
• All-cause mortality [Time frame: 30 days and 12 months after randomization]
• Time to clinical improvement [Time frame: Up to 12 months after randomization]
• Health-related quality of life (EQ-5D-5L) [Time frame: 6 and 12 months after randomization]
• Cognitive function (Montreal Cognitive Assessment) [Time frame: 6 and 12 months after randomization]
• Seizure frequency [Time frame: Up to 12 months after randomization]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Egypt · 4 centers

• Alexandria University, Smouha Comprehensive Stroke Center — Alexandria
• Ain Shams University — Cairo
• Cairo University — Cairo
• Neurology Department, Al-Azhar University — Cairo

Saudi Arabia · 3 centers

• King Khalid University — Abhā
• King Abdulaziz Medical City — Jeddah
• King Abdullah Medical City — Mecca

Turkey (Türkiye) · 2 centers

• Department of Neurology, Eskisehir Osmangazi University — Eskişehir
• Neurology Department, Dr. Lutfi Kirdar City Hospital — Istanbul

Jordan · 1 center

• Amman Specialized IR Center — Amman

Morocco · 1 center

• Centre Hospitalier Universitaire Ibn Sina de Rabat — Rabat

Pakistan · 1 center

• Aga Khan University — Karachi

Qatar · 1 center

• Weill Cornell Medicine-Qatar — Doha

Tunisia · 1 center

• Institut National de Neurologie — Tunis

Identifiers

NCT: NCT07548346 · MENASINO-REVIVE-2026-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗