Endovascular Treatment or Standard Medical Care for Cerebral Venous Sinus Thrombosis(ESCORT)
NCT Number: NCT06583889
Acronym: ESCORT
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Cerebral Venous Sinus Thrombosis
Interventions: DRUG: Heparin|PROCEDURE: Endovascular treatment
Sponsor: Beijing Tiantan Hospital
Sex: ALL
Age: ADULT
Enrollment: 224
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-09
Completion Date: 2029-08
Locations: Beijing Tiantan Hospital, Beijing, Beijing, 100010, China

Summary:
Background: It has not been extensively studied in differing populations that endovascular treatment (EVT) for acute and subacute CVST with multimodal imaging selection improves the functional outcome better than standard medical care based on the guidelines. Published experience with endovascular treatment is promising. However, its efficacy has not been confirmed and early selection criteria for EVT are unknown.

Objective:The main objective of the Endovascular treatment or Standard medical Care for Cerebral Venous Sinus Thrombosis (ESCORT) trial is to determine if EVT improves the functional outcome of acute and subacute CVST patients with multimodal imaging selection.

Study Design:The ESCORT trial is a multicenter, prospective, randomized, open-label, blinded endpoint trial.

Study population: Patients are eligible if they have a radiologically criteria proven acute and subacute CVST, obvious symptoms of intracranial hypertension(lumbar puncture pressure≥250mmH2O).

Intervention: Patients will be randomized to receive either EVT or standard medical care (therapeutic doses of heparin). EVT consists of local application of alteplase or urokinase within the thrombosed sinuses, balloon angioplasty, and/or mechanical thrombectomy. Glasgow coma score, NIH stroke scale, ophthalmologic examination, Headache Impact Test-6(HIT-6), EuroQol-5 dimension-5 level(EQ-5D-5L) scale score, multimodal imaging and relevant laboratory parameters will be assessed at baseline.

Endpoints: The primary endpoint is the proportion with good prognosis at 3 months (definition: a. mRS≤1; b. headache score (\<50, HIT-6); c. Frisén=0 grade for papilledema; d. defect of field vision PMD\>-2dB). Secondary outcomes are three-months mRS, HIT-6,Frisén grade for papilledema, situation of EQ-5D-5L, mortality and recanalization rate. Major intracranial and extracranial hemorrhagic complications within one-week after the intervention are the principal safety outcomes. Results will be analyzed according to the'intention-to-treat' principle. Blinded assessors not involved in the treatment of the patient will assess endpoints with standardized questionnaires.

Study size: To detect a 20% relative increase of good prognosis (from 65 to 85%), 224 patients (112 in each treatment arm) have to be included (two-sided alpha, 80% power).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Included patients may benefit directly from EVT. Complications of EVT, most notably intracranial hemorrhages, constitute the most important risk of the study.

Primary Outcome Measures: Efficacy endpoint, The proportion of good prognosis (definition: a. mRS≤1; b. headache score (\<50, HIT-6); c. Frisén=0 grade for papilledema; d. defect of field vision PMD\>-2dB), 90 days (±14 days) after randomization|Safety endpoint, New intracranial hemorrhage or aggravation of intracranial hemorrhage after intervention treatment (including: symptomatic hemorrhage and all cerebral hemorrhage found by imaging. Symptomatic intracranial hemorrhage refers to any type of intracranial hemorrhage with NIHSS score increased by 4 points or more, even leading to death)

Massive extracranial hemorrhage after intervention treatment (such as obvious clinical symptoms of extracranial organ system hemorrhage such as retroperitoneum, gastrointestinal tract, etc., accompanied by 2g/dl or more decrease in hemoglobin within 48 hours, or the need for infusion of 2 units or more of red blood cells, or the need for surgical intervention or even death), Within 7 days after intervention treatment
Secondary Outcome Measures: Favorable clinical outcome, mRS≤1, 90 days (±14 days) after randomization|Headache Impact Test-6 (HIT-6), HIT-6 score\<50, 90 days (±14 days) after randomization|Frisén grade for papilledema, The Frisén=0 grade, 90 days (±14 days) after randomization|Perimetric Mean Deviation (PMD), The perimetric mean deviation(PMD)\>-2dB of visual field defect, 90 days (±14 days) after randomization|Required surgical intervention in relation to CVST, The proportion of surgical intervention within 90 days after randomization that are required in relation to cerebral venous thrombosis (e.g. ventricular shunting procedures or craniotomy), within 90 days|Recanalization rate of cerebral venous sinus, The proportion of complete and partial recanalization of venous sinus (according to Qureshi classification criteria), 90 days (±14 days) after randomization|EuroQol-5 dimension-5 level(EQ-5D-5L) scale score, 90 days (±14 days) after randomization|All-cause mortality, 90 days after randomization|The incidence of cerebral hernia, 90 days after randomization|The proportion of decompressive craniectomy, 90 days after randomization|The incidence of other serious adverse events, 90 days after randomization
Other Outcome Measures: The proportion of good prognosis, The proportion of good prognosis (defined as: a. mRS≤1, b. headache score (\<50, HIT-6 score); c. Frisén grade=0 for papilledema; d. defect of field vision PMD\>-2dB)., 12 months (±1 month) after randomization|Favorable clinical outcome, mRS≤1, 12 months (±1 month) after randomization|Headache Impact Test-6 (HIT-6), HIT-6 score\<50, 12 months (±1 month) after randomization|Frisén grade for papilledema, The Frisén=0 grade, 12 months (±1 month) after randomization|Perimetric Mean Deviation (PMD), The perimetric mean deviation(PMD)\>-2dB of visual field defect, 12 months (±1 month) after randomization|Required surgical intervention in relation to CVST, The proportion of surgical intervention within 90 days after randomization that are required in relation to cerebral venous thrombosis (e.g. ventricular shunting procedures or craniotomy), 12 months (±1 month) after randomization|Recanalization rate of cerebral venous sinus, The proportion of complete and partial recanalization of venous sinus (according to Qureshi classification criteria), 12 months (±1 month) after randomization|Recurrence rate of venous sinus thrombosis, 12 months after randomization|EuroQol-5 dimension-5 level (EQ-5D-5L) scale score, 12 months (±1 month) after randomization|Interim analyses:good prognosis (definition: a. mRS≤1; b. headache score (<50, HIT-6); c. Frisén=0 grade for papilledema; d. defect of field vision PMD>-2dB), The DSMB will perform two interim analyses after 75 and 150 patients (1/3rd and 2/3rd of all patients) have been randomized and completed the 12-month follow-up evaluation. As a stopping rule for efficacy, the Haybittle-Peto method will be used:1.Interim analysis 1: p=0,001;2.Interim analysis 2: p=0,001.In addition, the DSMB will assess futility during the interim analyses. The trial will be discontinued for futility if the conditional power is below 20%. This conditional power will be calculated under the assumption that in the remaining two-thirds/one-thirds of the study population the distributions of the primary endpoint will be the same as observed at the interim analysis.For theinterim analyses the DSMB will use the primary outcome measure (good prognosis: a. mRS≤1; b. headache score (\<50, HIT-6); c. Frisén=0 grade for papilledema; d. defect of field vision PMD\>-2dB at 12 months) for the determination of efficacy and futility., After inclusion of 1/3rd and 2/3rd of patients