Endovascular Treatment or Standard Medical Care for Cerebral Venous Sinus Thrombosis(ESCORT) (ESCORT)

Efficacy and Safety of endovasCular Treatment vs Standard Medical Care for Cerebral venOus Sinus thRombosis With mulTimodal Imaging Selection(ESCORT)

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 Overview

• Status: Recruiting
• Conditions: Cerebral Venous Sinus Thrombosis
• Intervention / Treatment: Drug: Heparin; Procedure: Endovascular treatment

• Study Type: Interventional
• Enrollment (Estimated): 224
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xu Tong, MD; Phone Number: +8617611338800; Email: dongri0514@sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100010
      • Recruiting
      • Beijing Tiantan Hospital
      • Contact: Dapeng Mo, MD; Phone Number: +8613691419036‬; Email: modapeng1971@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

General inclusion criteria

1. age between 18 years and 60 years
2. Cerebral venous sinus thrombosis (CVST), confirmed by computed tomographic and magnetic resonance imaging (T1, T2, SWI, DWI, FLAIR), magnetic resonance venography, computed tomographic venography or digital subtraction angiography.
3. Patients with CVST who meet the following conditions (1) Within 3 weeks of acute onset (2) There are one of the obvious clinical symptoms: A. symptoms of intracranial hypertension: headache, papilledema, visual acuity and visual field damage; B. Neurological impairment symptoms; C. Seizure; D. Disturbance of consciousness (GCS score≥9)
4. Lumbar puncture pressure≥250mmH2O
5. Patients or their relatives can sign written informed consent

Image inclusion criteria

1.CT and MRI (T1, T2, MRV, SWI, DWI) are used to screen CVST as acute phase (T1 low signal, T2 equal signal or slightly high signal; CT showed that the corresponding area is high signal) or subacute phase (T1 and T2 high signal) 2.3D-TOF or CE-MRA or CTV are used to screen the types of venous sinus thrombosis occlusion of main drainage which is prone to intracranial hypertension due to venous sinus thrombosis as follows: A.Superior sagittal sinus occlusion: thrombus obliterates the posterior 1/2 segment of superior sagittal sinus

B.Transverse sinus occlusive type:

1. complete thrombosis of the bilateral transverse sinus with or without the corresponding sigmoid sinus involvement
2. complete thrombosis of the superior transverse sinus with or without the corresponding sigmoid sinus involvement C.complete thrombosis of the superior sagittal sinus and unilateral transverse sinus with or without the corresponding sigmoid sinus involvement D.complete thrombosis of the superior sagittal sinus and bilateral transverse sinus with the corresponding sigmoid sinus is occluded

Exclusion Criteria:

1. Received any thrombolytic therapy within 7 days
2. Patients who cannot cooperate or accept MRI examination
3. Patients with dementia or mental illness are known to be unable to complete neurological function assessment and follow-up
4. Patients with high myopia and eye diseases affecting fundus examination and visual field examination
5. The patient has a clear history of primary headache such as migraine, tension headache and cluster headache, and a clear history of secondary headache
6. Patients who receive major surgery (excluding lumbar puncture) or a history of severe brain injury within 2 weeks
7. Known history of severe allergy to contrast media (excluding rash)
8. Gastrointestinal bleeding occurred within 3 months (excluding bleeding from recto anal hemorrhoids)
9. Serious liver function or renal dysfunction with written records and affecting normal coagulation function
10. Hemorrhagic disease (hemorrhagic disease history) with written records
11. Excepting for CVST, patients with any life expectancy less than 1 year (such as advanced cancer)
12. Pregnant women (puerperal women can be enrolled)
13. Patients with contraindications to anticoagulation or thrombolysis
14. Intracranial infectious or malignant tumor secondary to cerebrospinal fluid
15. CVST secondary to autoimmune diseases and hematological diseases (such as primary thrombocytosis, myelodysplastic syndrome, leukemia, etc.) and genetic factors
16. Concurrent thrombocytopenia (<100×109/L)
17. MRI features showed that the occluded vessels of venous sinus were in chronic phase (T1 and T2 images showed equal signal)
18. Severe brain tissue injury symptoms such as obvious space occupying effect due to massive cerebral edema, cerebral infarction or cerebral hemorrhage
19. Patients with CVST accompanied by ventricular compression and hydrocephalus requiring surgery
20. Participating in clinical trials of any other drugs or medical devices, or may participate in clinical trials of any other drugs or medical devices within 6 months after being enrolled in this clinical trial
21. The researchers judge that there are other situations that are not suitable for enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard medical care	Drug: Heparin; 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.
Experimental: Endovascular treatment with standard medical care	Procedure: Endovascular treatment; 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.; Other Names: Alteplase; Urokinase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Outcome Measure	Measure Description	Time Frame
All-cause mortality		90 days after randomization
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
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

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Zhongrong Miao, MD, Beijing Tiantan Hospital; Principal Investigator: Dapeng Mo, MD, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: September 2, 2024
• First Submitted That Met QC Criteria: September 2, 2024
• First Posted (Actual): September 4, 2024

Study Record Updates

• Last Update Posted (Actual): September 4, 2024
• Last Update Submitted That Met QC Criteria: September 2, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Heparin; Endovascular treatment; Cerebral venous sinus thrombosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Embolism and Thrombosis; Intracranial Thrombosis; Intracranial Embolism and Thrombosis; Thromboembolism; Thrombosis; Sinus Thrombosis, Intracranial; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin
• Other Study ID Numbers: YD2023001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No