Clinical trial NCT06583889: Endovascular Treatment or Standard Medical Care for Cerebral Venous Sinus Thrombosis(ESCORT)
Official title: Efficacy and Safety of endovasCular Treatment vs Standard Medical Care for Cerebral venOus Sinus thRombosis With mulTimodal Imaging Selection(ESCORT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cerebral Venous Sinus Thrombosis
Keywords: Cerebral venous sinus thrombosis
Heparin
Randomized controlled trial
Endovascular treatment
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2024-09-04
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Efficacy endpoint
timeFrame: 90 days (±14 days) after randomization
measure: Safety endpoint
timeFrame: Within 7 days after intervention treatment
Secondary outcomes:
measure: Favorable clinical outcome
timeFrame: 90 days (±14 days) after randomization
measure: Headache Impact Test-6 (HIT-6)
timeFrame: 90 days (±14 days) after randomization
measure: Frisén grade for papilledema
timeFrame: 90 days (±14 days) after randomization
measure: Perimetric Mean Deviation (PMD)
timeFrame: 90 days (±14 days) after randomization
measure: Required surgical intervention in relation to CVST
timeFrame: within 90 days
measure: Recanalization rate of cerebral venous sinus
timeFrame: 90 days (±14 days) after randomization
measure: EuroQol-5 dimension-5 level(EQ-5D-5L) scale score
timeFrame: 90 days (±14 days) after randomization
measure: All-cause mortality
timeFrame: 90 days after randomization
measure: The incidence of cerebral hernia
timeFrame: 90 days after randomization
measure: The proportion of decompressive craniectomy
timeFrame: 90 days after randomization
measure: The incidence of other serious adverse events
timeFrame: 90 days after randomization
Other outcomes:
measure: The proportion of good prognosis
timeFrame: 12 months (±1 month) after randomization
measure: Favorable clinical outcome
timeFrame: 12 months (±1 month) after randomization
measure: Headache Impact Test-6 (HIT-6)
timeFrame: 12 months (±1 month) after randomization
measure: Frisén grade for papilledema
timeFrame: 12 months (±1 month) after randomization
measure: Perimetric Mean Deviation (PMD)
timeFrame: 12 months (±1 month) after randomization
measure: Required surgical intervention in relation to CVST
timeFrame: 12 months (±1 month) after randomization
measure: Recanalization rate of cerebral venous sinus
timeFrame: 12 months (±1 month) after randomization
measure: Recurrence rate of venous sinus thrombosis
timeFrame: 12 months after randomization
measure: EuroQol-5 dimension-5 level (EQ-5D-5L) scale score
timeFrame: 12 months (±1 month) after randomization
measure: 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)
timeFrame: After inclusion of 1/3rd and 2/3rd of patients
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital
state: Beijing
Study officials:
affiliation: Beijing Tiantan Hospital
name: Dapeng Mo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Tiantan Hospital
name: Zhongrong Miao, MD
role: PRINCIPAL_INVESTIGATOR
References: