Efficacy of a Minimally Invasive Therapy Adjuvant to the Standards of Care by Cyanoacrylate Embolization (LEADH)

LEADH: Efficacy of a Minimally Invasive Therapy Adjuvant to the Standards of Care by Cyanoacrylate Embolization : Liquid Embolic Agent for the Treatment of Chronic subDural Hematoma a Randomized Control Study

Chronic subdural hematomas (CSH) are collections of blood in the subdural space. CSH are becoming the most common cranial neurosurgical condition among adults, and a significant public health problem, due to an increasing use of anticoagulant and antiplatelet medication in an ageing population. Symptomatic CSH, or CSH with a significant mass effect, are treated surgically. However, recurrences are common (10 to 20%). Conservative management (medical) is used in patients who are asymptomatic or have minor symptoms. However, therapeutic failures, requiring surgical treatment, are common. The pathophysiology of CSH involves inflammation, angiogenesis, and clotting dysfunction. Self-perpetuation and rebleeding is thought to be caused by neo-membranes from the inflammatory remodeling of the dura-mater mainly fed by the distal branches of the middle meningeal artery (MMA). There are 13 ongoing registered RCTs in CSH, with the most common covering application of steroids, surgical techniques and tranexamic acid. Further to this, there are trials running on other pharmacological agents, and peri-operative management. Some industrial or academic trials are or will enroll in France in the next year in France. But to our best knowledge, none of these trials will the eventual benefits of the MMA embolization in both cases of medical and/or surgical management, and none will focus on the use of cyanoacrylates (CYA) for this purpose.

Preliminary case series and nonrandomized retrospective studies have suggested that MMA embolization alone or as adjuvant therapy to surgery can decrease recurrences.

The investigators hypothesize that in both conditions of conservative or surgical managements, endovascular embolization of patients with CSH significantly reduces the risk of recurrence of CSH. The investigators choose the CYA as liquid embolic agent because of the pain and cost of the use of Ethylen Vinyl alcohol copolymer (EVOH) agents and its simplicity to be used.

Study Overview

• Status: Recruiting
• Conditions: Chronic Subdural Hematoma
• Intervention / Treatment: Other: Medical treatment; Other: Surgical treatment; Other: embolization of the MMA

Detailed Description

• Indication of surgical or conservative management will be decided by the neurosurgeon.
• Experimental arm:

CSH requiring hematoma removal will be surgically managed with a surgical technique applied depending on the surgeon's discretion.

Medical management will be adopted according to neurosurgeons habits. MMA embolization (on the CSH side or bilaterally if necessary) in the Experimental Arms will be performed with Cyanoacrylates and preferentially using conscious sedation or local anesthesia.

• Control arm: CSH requiring hematoma removal will be surgically managed with a surgical technique applied depending on the surgeon's discretion.

Medical management will be adopted according to neurosurgeons habits

• Primary and secondary end points will be assessed at 2 months+/- 1 month and assessed at 6 +/- 2 months. The blind items will be the mRS and the RACE score. The volume of the CSH will be semi-automatically assessed using the ABC/2 method and the estimated maximal thickness of the CSH on axial images.

• Study Type: Interventional
• Enrollment (Estimated): 550
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: jean-Christophe GENTRIC, PhD; Phone Number: 0298347520; Email: jean-christophe.gentric@chu-brest.fr

Study Locations

• France
  • Amiens, France, 80054
    • Recruiting
    • CHU Amiens-Picardie
    • Contact: Cyril CHIVOT, Dr; Email: chivot.cyril@chu-amiens.fr
    • Principal Investigator: Cyril CHIVOT, Dr
  • Bordeaux, France, 33076
    • Recruiting
    • CHU Bordeaux
    • Contact: Gaultier MARNAT, Dr; Email: gaultier.marnat@chu-bordeaux.fr
    • Principal Investigator: Gaultier MARNAT, Dr
  • Brest, France, 29609
    • Recruiting
    • CHU Brest
    • Contact: Jean-Christophe GENTRIC, PhD; Email: jean-christophe.gentric@chu-brest.fr
    • Principal Investigator: Jean-Christophe GENTRIC, PhD
  • Caen, France, 14000
    • Recruiting
    • CHU caen
    • Contact: Charlotte BARBIER, Dr; Email: barbier-c@chu-caen.fr
    • Principal Investigator: Charlotte BARBIER, Dr
  • Nancy, France, 54035
    • Recruiting
    • CHU Nancy
    • Contact: Benjamin GORY, Pr; Email: B.GORY@chru-nancy.fr
    • Principal Investigator: Benjamin GORY, Pr
  • Nantes, France, 44000
    • Recruiting
    • CHU Nantes
    • Contact: Romain BOURCIER, Dr; Email: romain.bourcier@chu-nantes.fr
    • Principal Investigator: Romain BOURCIER, Dr
  • Paris, France, 75013
    • Recruiting
    • Hôpital Pitié Salpétrière
    • Contact: Frédéric CLARENCON, Pr; Email: frederic.clarencon@aphp.fr
    • Principal Investigator: Frédéric CLARENCON, Pr
  • Tours, France, 37000
    • Recruiting
    • Chu Tours
    • Contact: Grégoire BOULOUIS, Dr
    • Principal Investigator: Grégoire BOULOUIS, Dr
• Martinique
  • Fort-de-France, Martinique, 97261
    • Not yet recruiting
    • CHU Martinique
    • Contact: Célia TUTTLE, Dr
    • Principal Investigator: Célia TUTTLE, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient with a more than 10 mm CSH confirmed by NCCT
• CSH localized to convexity
• Patient aged 18 years or more at the time of the enrollment
• Patient beneficiary from health insurance

Exclusion Criteria:

• Any contraindication as required per angiogram procedure (severe renal failure, allergy…)
• Pre-existing severe disability resulting in baseline mRS score > 3
• Life expectancy of less than 6 months due to another cause than CSH
• Patient under legal protection or deprived of liberty by a judicial or administrative decision
• Pregnant or breastfeeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Medical treatment alone; Medical treatment without embolization of the MMA.	Other: Medical treatment; Medical treatment alone
Other: Surgical treatment alone; Surgical treatment without embolization of the MMA.	Other: Surgical treatment; Surgical treatment alone
Experimental: Medical treatment associated with an embolization of the MMA; Medical treatment + embolization under local anesthesia or conscious sedation. The embolization will be carried out by femoral or radial arterial guided by pre-embolization cervical CTA. The middle meningeal artery will be catheterized then embolized by cyanoacrylates until the occlusion of the MMA.	Other: Medical treatment; Medical treatment alone; Other: embolization of the MMA; The middle meningeal artery will be catheterized then embolized by cyanoacrylates until the occlusion of the MMA.
Experimental: Surgical treatment associated with an embolization of the MMA; Surgical treatment + embolization under local anesthesia or conscious sedation. The embolization will be carried out by femoral or radial arterial guided by pre-embolization cervical CTA. The middle meningeal artery will be catheterized then embolized by cyanoacrylates until the occlusion of the MMA.	Other: Surgical treatment; Surgical treatment alone; Other: embolization of the MMA; The middle meningeal artery will be catheterized then embolized by cyanoacrylates until the occlusion of the MMA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of CSH recurrence defined by the composite endpoint	CSH recurrence defined by the composite endpoint: A symptomatic CSH during the 6 month FU period; A secondary surgical management during the 6 months FU period; A remaining or reaccumulated hematoma on NCCT at 6 months	At 6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of symptomatic CSH during the FU period	Number of symptomatic CSH during the FU period	At 6 month
Number of secondary surgical management during the FU period	Number of secondary surgical management during the FU period	At 6 month
Number of remaining or reaccumulated hematoma on NCCT	Number of remaining or reaccumulated hematoma on NCCT	At 6 month
Clinical efficacy	Mortality rate	At 6 month
Clinical efficacy	Shift Modified Rankin Scale (mRS) (min = 0 = better outcome, max = 5 = worse outcome)	At 6 month
Clinical efficacy	Rapid Arterial oCclusion Exam (RACE) score evaluation (min = 0 = better outcome, max = 9 = worse outcome)	At 6 month
Clinical efficacy	Quality of life of patients will be evaluated by the EuroQol-5Dimensions-5L questionnaire	At 6 month
Clinical efficacy	Neurological exam : Barthel Scale (min = 0 = worse outcome, max = 100 = better outcome)	At 6 month
Success rate of the embolization (success = technical success of the procedure. Failure of the procedure = total or partial (catheterization, injection, other)).	Success rate of the embolization (success = technical success of the procedure. Failure of the procedure = total or partial (catheterization, injection, other)).	At 6 month
Complication rate of the embolization	Complication rate of the embolization	At 6 month
Volumetry of the CSH, calculated by the ABC/2 method.	Volumetry of the CSH, calculated by the ABC/2 method.	At 6 month
Maximum thickness of the CSH in mm.	Maximum thickness of the CSH in mm.	At 6 month
Comparison of the rate of AE in both groups	Comparison of the rate of AE in both groups	At 6 month
Comparison of the rate of SAE in both groups	Comparison of the rate of SAE in both groups	At 6 month

Collaborators and Investigators

• Sponsor: University Hospital, Brest

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2023
• Primary Completion (Estimated): September 28, 2026
• Study Completion (Estimated): September 28, 2026

Study Registration Dates

• First Submitted: April 29, 2022
• First Submitted That Met QC Criteria: May 13, 2022
• First Posted (Actual): May 16, 2022

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Cyanoacrylate; Embolization; Middle meningeal artery; Recurrence of chronic subdural hematoma
• 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: 29BRC22.0028

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected data that underlie results in a publication
• IPD Sharing Time Frame: Data will be available beginning three years and ending fifteen years following the final study report completion.
• IPD Sharing Access Criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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