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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
224
The patients randomized to standard medical care will receive (or continue) either any type of body-weight adjusted low molecular weight heparin in therapeutic dose, or intravenous adjusted dose unfractionated heparin (aPTT value kept within 1 time the normal value), according to the existing international guidelines.
Standard endovascular techniques to mechanically remove clot material, such as mechanical thrombectomy and/or balloon angioplasty and/or local application of alteplase or urokinase within the thrombosed sinuses.
Beijing Tiantan Hospital
Beijing, Beijing Municipality, China
RECRUITINGEfficacy 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)
Time frame: 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)
Time frame: Within 7 days after intervention treatment
Favorable clinical outcome
mRS≤1
Time frame: 90 days (±14 days) after randomization
Headache Impact Test-6 (HIT-6)
HIT-6 score\<50
Time frame: 90 days (±14 days) after randomization
Frisén grade for papilledema
The Frisén=0 grade
Time frame: 90 days (±14 days) after randomization
Perimetric Mean Deviation (PMD)
The perimetric mean deviation(PMD)\>-2dB of visual field defect
Time frame: 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)
Time frame: within 90 days
Recanalization rate of cerebral venous sinus
The proportion of complete and partial recanalization of venous sinus (according to Qureshi classification criteria)
Time frame: 90 days (±14 days) after randomization
EuroQol-5 dimension-5 level(EQ-5D-5L) scale score
Time frame: 90 days (±14 days) after randomization
All-cause mortality
Time frame: 90 days after randomization
The incidence of cerebral hernia
Time frame: 90 days after randomization
The proportion of decompressive craniectomy
Time frame: 90 days after randomization
The incidence of other serious adverse events
Time frame: 90 days after randomization
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