Clinical trial NCT04511572: Embolization of Middle Meningeal Artery in Chronic Subdural Hematoma
Official title: Improving the Outcome of Chronic Subdural Hematoma by Embolization of Middle Meningeal Artery (ELIMINATE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Subdural Hematomas
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2020-08-13
Enrollment: 170
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Chronic subdural hematoma (cSDH) is a common neurological affliction which affects mostly frail and elderly patients. Surgical evacuation by using burr hole craniostomy (BHC) is the most frequently used treatment but carries a recurrence rate varying between 10-30% in the literature. Especially in this frail population re-operation is undesirable. Embolization of the middle meningeal artery is an adjuvant treatment which has been reported in multiple case reports and larger case series, showing a beneficial effect on recurrence rate, reducing it to \<5%, without complications.

Objectives: Primary: To evaluate whether additional embolization of the middle meningeal artery after surgery for cSDH reduces the recurrent surgery rate. Secondary: to evaluate whether the use of middle meningeal artery embolization after surgical treatment in symptomatic cSDH patients increases quality of life (SF-36 and the EQ-5D-5L), performance in activities of daily living (AMC Linear Disability Score), functional outcome (mRS), cognitive functioning (MOCA) and reduces mortality, occurrence of complications, recurrence rate, size and volume of the hematoma, neurological impairment (mNIHSS, Markwalder score) and the use of care and health-related costs (iMCQ and iPCQ).

Study design: Multicenter, randomized controlled open-label superiority trial. Study population: Patients diagnosed with a cSDH who require surgery. Intervention: The intervention group will receive embolization in addition to standard surgical treatment. The control group will receive surgery only.

Main study endpoint: The number of patients who require reoperation within 24 weeks after the intervention.

Symptomatic cSDH patients will undergo peri-operative embolization of the middle meningeal artery until 72 hours after surgical treatment. Complications are monitored during hospital admission and follow-up. Radiological and clinical follow-up is at eight, 16 and 24 weeks post-intervention with a CT-scan of the head and assessment of mRS, MOCA, mNIHSS, Markwalder score, SF-36, EQ-5D-5L, ALDS, iMCQ and iPCQ. Standard care after surgery entails outpatient follow-up with on average two CT-scans, indicated by clinical signs and symptoms.

Detailed description: Chronic subdural hematoma A chronic subdural hematoma (cSDH) is a bleeding of the bridging veins between the dura mater and the arachnoid.

Subdural hematomas are one of the most common forms of hemorrhage affecting mostly elderly people. The estimated incidence in Western countries is 8.1 per 100,000 per year in patients aged 65 years or older, but increases to 58/100,000/year for those aged 70 years or older. With the elderly population growing, the incidence of cSDH is expected to double by 2030. CSDH presents itself as an heterogeneous disease with various symptoms. Most common are gait disturbances, focal deficits, headaches and hemiparesis. Risk factors for occurrence are chronic alcoholism, male gender and anticoagulation and antiplatelet therapy. CSDH is a challenging disease of which the pathophysiology is not completely clear. Even though cSDH initially arises due to tearing of the bridging veins, its chronicity likely has an arterial origin. At first a subdural hematoma forms after a (minor) head trauma. The hematoma persists due to failure of the reparative and absorbing mechanisms. The current hypothesis states that the inability of the human body to heal the hematoma is due to increased neovascularization in the subdural membrane of the hematoma. This leads to repeated micro hemorrhages and further increase in fibrinolytic activity, which makes the body unable to stop recurrent microbleeds. Repeated micro hemorrhages are caused by collateral blood vessels originating from the middle meningeal artery. The correlation between the cycle of re-bleeding and fibrinolysis, and reabsorption of the subdural collection will determine whether the cSDH will resolve, persist or enlarge.

Treatment options The first treatment option for mildly symptomatic cSDH is a conservative 'wait-and-scan' approach in which the patient is followed with CT-scans and outpatient clinic visits. The majority (75%) of these conservatively managed patients however, eventually still require surgery (own data). Medical treatment is a second non-surgical treatment option currently being studied in large RCTs, for instance with steroids (dexamethasone), mannitol, tranexamic acid (TORCH-study), statins and ACE-inhibitors.

Surgical treatment is most frequently used in symptomatic patients with a cSDH as surgery provides instant decompression of the brain and rapid relief of (life-threatening) symptoms. However, surgery is costly and in these often frail patients with multi-morbidity, surgery comes with significant risks for future cognitive functioning and therefore loss of independence. Furthermore, recurrence rates after surgery range from 9-30%, resulting in frequent re-operations. Therefore, the optimal treatment for cSDH remains a 'burning clinical question' for which neurologists and neurosurgeons do not have evidence-based answers. Multiple studies have described successful treatment with embolization of the middle meningeal artery as an adjunct to surgical evacuation. The goal of embolization is to devascularize the subdural membranes to a sufficient extent such that the balance is shifted from the continued rebleeding and accumulation of blood products towards reabsorption of the subdural effusion. The use of embolization in cSDH patients was first reported in 2000, and since then multiple case reports, case series and cohort studies have been published investigating the safety and effectiveness. The largest cohort study compared 72 patients with embolization (as sole treatment or with surgical treatment combined) to 469 (retrospectively) non-surgical treated patients. In this study no complications were reported and only one patient needed repeat surgery. A relatively large case series of 60 patients was reported, again with no complications and a success rate of 92% (patients who were able to avoid surgery). Recent systematic reviews on middle meningeal artery embolization highlight the lower recurrence and complication rate in all embolization cases (\<5% and 0%, respectively). Nevertheless, these results are based on non-randomized studies with moderate quality and a small sample size. The effect of embolization as an adjunct to surgical evacuation has never been evaluated in a randomized controlled trial.

In conclusion, although surgery is still the primary treatment option for the majority of patients with cSDH, it carries a significant risk of additional morbidity and mortality and has a relatively high risk of treatment failure. In the aging population, comorbidities are more frequent and the risk of peri-operative complications is acknowledged, limiting a favorable clinical outcome. Middle meningeal artery embolization appears to be a promising adjunct therapy to surgery, which might reduce the necessity for repeat surgical treatment and improve clinical outcome is this vulnerable patient group.

Eligibility criteria: Inclusion Criteria:

* · CT-confirmed diagnosis of chronic Subdural Hematoma;

  * Primary surgical treatment based on clinical symptoms (progressive neurological deficits).

Exclusion Criteria:

* · Significant contraindication to angiography (eg. allergy for contrast);

  * Structural causes for subdural hemorrhage, e.g. arachnoid cysts, cortical vascular malformations and a history of cranial surgery in the previous 365 days;
  * Inability to obtain informed consent from the patient or legal representative (when the patient has a depressed level of consciousness), including language barrier;
  * Monocular blindness on contralateral side of the hematoma;

Primary outcomes:
measure: Reoperation
timeFrame: 8 weeks after discharge.
measure: Reoperation
timeFrame: 16 weeks after discharge.
measure: Reoperation
timeFrame: 24 weeks after discharge.
Secondary outcomes:
measure: Hematoma volume reduction
timeFrame: 8 weeks after discharge.
measure: Hematoma volume reduction
timeFrame: 16 weeks after discharge.
measure: Hematoma volume reduction
timeFrame: 24 weeks after discharge.
measure: Complications
timeFrame: 8 weeks after discharge.
measure: Complications
timeFrame: 16 weeks after discharge.
measure: Complications
timeFrame: 24 weeks after discharge.
measure: modified National Institute Health Stroke Scale score
timeFrame: 8 weeks after discharge.
measure: modified National Institute Health Stroke Scale score
timeFrame: 16 weeks after discharge.
measure: modified Rankin Scale score
timeFrame: 24 weeks after discharge.
measure: modified National Institute Health Stroke Scale score
timeFrame: 24 weeks after discharge.
measure: Montreal Cognitive Assessment
timeFrame: 8 weeks after discharge.
measure: Montreal Cognitive Assessment
timeFrame: 16 weeks after discharge.
measure: Montreal Cognitive Assessment
timeFrame: 24 weeks after discharge.
measure: mortality
timeFrame: 8 weeks after discharge.
measure: mortality
timeFrame: 16 weeks after discharge.
measure: mortality
timeFrame: 246 weeks after discharge.
measure: Activities of Daily Living Scale
timeFrame: at 24 weeks after discharge.
measure: Short Form Health Survey
timeFrame: at 24 weeks after discharge.
measure: EuroQol (EQ-5D-5L) questionnaire
timeFrame: at 24 weeks after discharge.
measure: Medical Consumption questionnaire
timeFrame: at 24 weeks after discharge.
measure: Productivity Cost Questionnaire
timeFrame: at 24 weeks after discharge.
measure: Markwalder grading scale score
timeFrame: at eight weeks after discharge
measure: Markwalder grading scale score
timeFrame: at 16 weeks after discharge
measure: Markwalder grading scale score
timeFrame: at 24 weeks after discharge
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam university medical Centers
Study officials:
affiliation: Amsterdam Universities Medical Centers
name: William P. Vandertop, MD PhD
role: STUDY_CHAIR
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