Clinical trial NCT04372147: Embolization of the Middle Meningeal Artery for the Prevention of Chronic Subdural Hematoma Recurrence in High Risk Patients (EMPROTECT)
Official title: Embolization of the Middle Meningeal Artery for the Prevention of Chronic Subdural Hematoma Recurrence in High Risk Patients, a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Subdural Hematoma
At Risk of Post-operative Recurrence
Burr-hole Surgery
Keywords: Chronic Subdural Hematoma
Burr-Hole Surgery
Recurrence
Middle Meningeal Artery
Embolization
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-05-01
Enrollment: 342
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multicenter open label randomized controlled trial. Eligible patients will be assigned either to the intervention or a control arm
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: SDH recurrence
timeFrame: 6 months
Secondary outcomes:
measure: repeated surgery
timeFrame: 6 months
measure: disability and dependency
timeFrame: 1 and 6 months
measure: mortality
timeFrame: 1 and 6 months
measure: hospital stay
timeFrame: 6 months
measure: complication rates
timeFrame: 6 months
Other outcomes:
Locations:
city: Clamart
country: France
facility: Hôpital d'instruction des armées de Percy
city: Clichy
country: France
facility: Hôpital Beaujon
city: Créteil
country: France
facility: Hôpital Henri-Mondor
city: Lille
country: France
facility: CHU Lille (Hôpital Roger Salengro)
city: Limoges
country: France
facility: CHU de Limoges
city: Marseille
country: France
facility: Hôpital Nord (CHU MARSEILLE)
city: Marseille
country: France
facility: CHU de Marseille
city: Paris
country: France
facility: Hôpital Lariboisière
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière
city: Paris
country: France
facility: Hôpital Sainte Anne
city: Paris
country: France
facility: Fondation Rothschild
city: Tours
country: France
facility: CHU Tours
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Eimad Shotar, MD
role: PRINCIPAL_INVESTIGATOR
References: