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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Chronic Subdural Hematoma

Intervention / Treatment
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* Other: Medical treatment
* Other: Surgical treatment
* Other: embolization of the MMA


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Medical treatment alone<br>Medical treatment without embolization of the MMA. | Other: Medical treatment<br>* Medical treatment alone<br>|
| Other: Surgical treatment alone<br>Surgical treatment without embolization of the MMA. | Other: Surgical treatment<br>* Surgical treatment alone<br>|
| Experimental: Medical treatment associated with an embolization of the MMA<br>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<br>* Medical treatment alone<br>Other: embolization of the MMA<br>* The middle meningeal artery will be catheterized then embolized by cyanoacrylates until the occlusion of the MMA.<br>|
| Experimental: Surgical treatment associated with an embolization of the MMA<br>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<br>* Surgical treatment alone<br>Other: embolization of the MMA<br>* The middle meningeal artery will be catheterized then embolized by cyanoacrylates until the occlusion of the MMA.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cyanoacrylate, Embolization, Middle meningeal artery, Recurrence of chronic subdural hematoma