Embolization of the Middle Meningeal Artery for the Prevention of Chronic Subdural Hematoma Recurrence in High Risk Patients (EMPROTECT)

Study Overview
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Brief Summary
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Standard of care for the management of symptomatic chronic subdural hematomas (SDHs) is neurosurgical burr-hole evacuation followed by drainage. Post-operative recurrence rates may be as high as 10 to 20 %. In particular, recurrence rate increases with antiplatelet and anticoagulant therapy. Middle meningeal artery (MMA) embolization has been proposed as a novel treatment of chronic SDH. The aim of this study is to assess the efficacy of MMA embolization in reducing the risk of chronic SDH recurrence at 6 months after burr-hole surgery as compared with standard medical post-operative treatment in patients at high risk of post-operative recurrence.

Detailed Description
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Introduction: chronic SDHs are some of the most frequently encountered neurosurgical emergencies. The gold standard treatment of symptomatic chronic SDHs is burr-hole surgery followed by temporary closed system drainage. Post-operative recurrence rates may be as high as 10 to 20% and are a major source of morbidity and repeated surgery. MMA embolization is a promising minimally invasive procedure recently proposed as a treatment of chronic SDH. It is hypothesized that post-operative MMA embolization may reduce recurrence rate in patients at high risk of recurrence. Aims: the primary objective of the trial is to assess the efficacy of MMA embolization in reducing the risk of chronic SDH recurrence at 6 months after burr-hole surgery as compared with standard medical treatment in patients at high risk of post-operative recurrence. Secondary objectives include evaluating the impact of post-operative MMA embolization on rate of recurrence requiring new surgery (at 6 months), rate of functional dependency (at 1 and 6 months) , mortality (at 1 and 6 months) , cumulative hospital stay duration, related to the SDH, and complication rate at 6 months. Methods: multicenter open label randomized controlled trial. Eligible patients will be assigned either to the intervention or a control arm through blocked randomization with randomblock sizes and stratified on the center, antiplatelet/anticoagulant therapy and unilateral vs bilateral SDH. Patients in the intervention group will undergo a CT angiography scan of the supra aortic trunks, followed by MMA embolization procedure within 7 days of the burr-hole surgery in addition to standard medical care. Patients in the control group will receive standard medical care only. Outcomes will be evaluated at 1 and 6 months. The primary outcome measure will be the rate of chronic SDH recurrence 6 months after index burr-hole surgery, as defined bellow. In order to demonstrate a decrease in recurrence rate from 15 to 5% between the intervention and control arms with a power of 80%, bilateral global alpha risk of 5%, with two planned sequential tests according to the method of Lan & Demets, and 20% patients lost to follow-up, 342 patients are required, 171 in each arm. The primary outcome will be analyzed according to intention to treat.

Official Title
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Embolization of the Middle Meningeal Artery for the Prevention of Chronic Subdural Hematoma Recurrence in High Risk Patients, a Randomized Controlled Trial

Conditions
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Chronic Subdural Hematoma, at Risk of Post-operative Recurrence, Burr-hole Surgery

Intervention / Treatment
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* Procedure: MMA embolization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient: Aged ≥ 18 years Operated for a SDH recurrence or operated for a first episode of SDH if at least one of the following recurrence risk factors is present: Chronic alcoholism defined by a daily alcohol consumption > 30g/day Or liver cirrhosis Or antiplatelet therapy Or anticoagulant therapy Or thrombocytopenia with a platelet count < 100 x10(3) per µL Or surgery without use of external drain With affiliation to a social security scheme Having signed an informed consent form or for whom a delegate close relative or a support person has signed an informed consent Exclusion Criteria: SDH evacuation by craniotomy or twist-drill craniostomy rather than burr-hole surgery Beyond 7 days after the index surgery (surgery for recurrent SDH or first surgery in case of a risk factor as indicated in the inclusion criteria) Functionally dependant patient with an mRS score ≥ 4 before the SDH Patient with a life expectancy < 6 months Patient with renal failure as defined by a creatinine clearance < 30 ml/min Pregnancy History of allergy to a iodinated contrast agent Procedure deemed unachievable under local anesthesia (because of patient agitation or discomfort for instance) in a patient with a contraindication to both conscious sedation and general anesthesia. Patient refusal Patient for whom follow-up is deemed problematic (living abroad or homeless for instance ) Patients under legal guardianship or trusteeship

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: multicenter open label randomized controlled trial. Eligible patients will be assigned either to the intervention or a control arm
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intervention group<br>MMA embolization procedure within 7 days of the burr-hole surgery in addition to standard medical care | Procedure: MMA embolization<br>* Patients in the intervention group will undergo a CT angiography scan of the supra aortic trunks, followed by MMA embolization procedure within 7 days of the burr-hole surgery in addition to standard medical care<br>|
| No Intervention: control group<br>standard medical care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SDH recurrence | Rate of chronic subdural hematoma (SDH) recurrence 6 months after index burr-hole surgery, defined as: Reappearance of a homolateral SDH with a midline shift > 5mm or a symptomatic homolateral SDH, including leading to death Or, the presence of a homolateral SDH > 10mm in maximal thickness on the 6 months control head CT scan Or, the need for repeated surgery for a homolateral SDH recurrence Or, the need for a new hospital admission in relation to a homolateral SDH recurrence | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| repeated surgery | - Rate of repeated surgery for a homolateral SDH recurrence during the 6 months follow-up period | 6 months | 
| disability and dependency | - Rate of disability and dependency at 1 and 6 months, defined by a modified Rankin Scale (mRS) score ≥ 4. The mRS is an ordered scale coded from 0 (no symptoms at all) through 5 (severe disability) 6 (death) | 1 and 6 months | 
| mortality | - Mortality rate at 1 and 6 months | 1 and 6 months | 
| hospital stay | - Total cumulative duration of hospital stay, during the 6 months follow-up period, directly or indirectly related to the SDH | 6 months | 
| complication rates | - Minor and major embolization procedure-related complication rates | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Subdural Hematoma, Burr-Hole Surgery, Recurrence, Middle Meningeal Artery, Embolization