Endovascular vs Conservative Treatment in Patients With Chronic Subdural Hematomas and Mild Symptoms

Endovascular vs Conservative Treatment in Patients With Chronic Subdural Hematomas and Mild Symptoms: a Multicentre Randomized Trial

Embotrial-1 is an Italian multicenter prospective randomized clinical trial with open-label treatment and blinded outcome assessment (PROBE) to assess the superiority of MMA embolization compared to conservative treatment. The intervention group is MMA embolization and comparator control group is the conservative management with best medical treatment. Patients are randomized 1:1.

Study Overview

• Status: Not yet recruiting
• Conditions: Subdural Hematoma, Chronic
• Intervention / Treatment: Device: embolization of the middle meningeal artery

Detailed Description

Patients randomized to the experimental arm will submit to cerebral angiography and bilateral MMA embolization of the cSHD, even if it is located to only one side. The ipsilateral MMA embolization of the cSDH is allowed when the endovascular procedure cannot be performed on both sides. Patients are preferably under monitored local anesthesia or alternatively under conscious sedation or general anesthesia. Briefly, through femoral or radial artery access a standard 5 French diagnostic catheter is placed in the proximal external carotid artery and a digital subtraction angiography (DSA) is performed. Then, a microcatheter is advanced selectively under roadmap guidance into the main trunk of MMA, and superselective angiography is performed to evaluate for potentially dangerous anastomoses between MMA and ophthalmic or petrous branches prior to embolization. After collateral vessels are excluded, the MMA is occluded with PVA particles or liquid embolizing materials . The successful embolization is defined as that both frontal and parietal branch of MMA are selectively occluded and for this purpose, the microcatheter should be placed as distally as possible. It is recommended to ensure embolic materials penetrating into the capillary network of the dura to be permanently blocked. Patients randomized to the conservative arm will be clinmically monitored and eventually receive a best supportive care according to the local practice.

The trial is powered to assess superiority. When assuming the event rate of 1% in intervention group and 10% event rate in the control group, with a power of 85% and two-sided alpha of 0.05, allowing for 10% drop-outs, the estimated sample size is 300 patients in total.

The safety and efficacy interim analysis will be planned when half of the target sample (150 patients) completed 6 months follow-up. The enrollment will be stopped if the futility assessment based on estimated conditional power will be <70%.

All patient data is registered in the electronic data capture software REDCap. This worldwide online system allows built-in logical checks and validations to promote data quality. All clinical data are entered via an encrypted connection, are anonymized, and fulfill the demands for data protection. All data entries and changes are logged in REDCap and meet the Good Clinical Practice (GCP) requirements for the use of the electronic case report form (eCRF) in medical trials. Trial coordinators, data managers and the investigators will be introduced to the platform and trained in data entry during the initial kick-of meeting prior to recruitment of the first patient. Trial staff will be provided with a personal ID.

Currently, 6 centers in Italy have been identified for the study. All the clinical investigators are board-certified and have renowned expertise in neurosurgery, neuroradiology and endovascular interventions.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lucio Castellan, MD; Phone Number: +390105552262; Email: lucio.castellan@hsanmartino.it
• Study Contact Backup: Name: Giancarlo Salsano, MD; Phone Number: +390105552262; Email: giancarlo.salsano@hsanmartino.it

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• No neurological deficits (Markwalder score ≤1);
• Unilateral or bilateral cSDH;
• Subdural Hematoma width ≤ 20 mm; midline shift ≤ 7mm;
• Independent functional status with mRS score ≤ 2 prior to symptom onset;
• Likely compliance of the participant in attending follow-up examination.

Exclusion Criteria:

• Radiological evidence of an acute or subacute subdural hematoma, subarachnoid hemorrhage, intracerebral hematoma or epidural hematoma;
• Contraindications to angiography (end stage chronic renal disease, any sign of anatomical variations that could make MMA embolization unsafe, pregnancy);
• Life expectancy < 1 year;
• Patients with any kind of ventricular derivation catheter.

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
Experimental: Embolization of the middle meningeal artery; Endovascular treatment of chronic subdural hematoma	Device: embolization of the middle meningeal artery; Embolization of the MMA is occluded with PVA particles or liquid embolizing materials
No Intervention: standard of care; control group will managed according to the current standard of care with "wait and see" approach and best medical treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of incomplete hematoma resolution or surgical rescue	Incomplete hematoma resolution is defined as a reduction of the cSDH thickness ≤50% at follow-up compared to the hematoma thickness measured at the time of randomization. Surgical rescue is intended as hematoma removal for relief of symptoms (mRS≥3 and Markwalder scale≥2) that develope with progressive growth of the cSDH	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
treatment complication	Procedure related complication during or 30 days after MMA embolization	30 days
treatment successful	Successful embolization rate of the target vessels based on angiographic findings	periprocedural

Collaborators and Investigators

• Sponsor: Ospedale Policlinico San Martino
• Investigators: Principal Investigator: Lucio Castellan, MD, Ospedale Policlinico San Martino

Publications and helpful links

General Publications

• Santarius T, Kirkpatrick PJ, Ganesan D, Chia HL, Jalloh I, Smielewski P, Richards HK, Marcus H, Parker RA, Price SJ, Kirollos RW, Pickard JD, Hutchinson PJ. Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial. Lancet. 2009 Sep 26;374(9695):1067-73. doi: 10.1016/S0140-6736(09)61115-6.
• Kim HC, Ko JH, Yoo DS, Lee SK. Spontaneous Resolution of Chronic Subdural Hematoma : Close Observation as a Treatment Strategy. J Korean Neurosurg Soc. 2016 Nov;59(6):628-636. doi: 10.3340/jkns.2016.59.6.628. Epub 2016 Oct 24.
• Rojas-Villabona A, Mohamed S, Kennion O, Padmanabhan R, Siddiqui A, Prasad M, Mukerji N. A systematic review of middle meningeal artery embolization for minimally symptomatic chronic subdural haematomas that do not require immediate evacuation. Brain Spine. 2023 Sep 6;3:102672. doi: 10.1016/j.bas.2023.102672. eCollection 2023.
• Akamatsu Y, Kashimura H, Kojima D, Yoshida J, Chika K, Komoribayashi N, Fujiwara S, Ogasawara K. Correlation Between Low-Density Hematoma at 1-Week Post-Middle Meningeal Artery Embolization and Rapid Resolution of Chronic Subdural Hematoma. World Neurosurg. 2024 Jan;181:e1088-e1092. doi: 10.1016/j.wneu.2023.11.045. Epub 2023 Nov 17.
• Omura Y, Ishiguro T. Middle meningeal artery embolization for chronic subdural hematoma: a systematic review. Front Neurol. 2023 Oct 10;14:1259647. doi: 10.3389/fneur.2023.1259647. eCollection 2023.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: February 6, 2024
• First Submitted That Met QC Criteria: February 20, 2024
• First Posted (Actual): February 23, 2024

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: chronic; embolization; subdural hematoma; middle meningeal artery
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Disease Attributes; Hemorrhage; Craniocerebral Trauma; Trauma, Nervous System; Intracranial Hemorrhages; Intracranial Hemorrhage, Traumatic; Chronic Disease; Hematoma; Hematoma, Subdural; Hematoma, Subdural, Chronic
• Other Study ID Numbers: 5916

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: Yes
• product manufactured in and exported from the U.S.: Yes