Chronic Subdural HematomasELIMINATENCT04511572
Embolization of Middle Meningeal Artery in Chronic Subdural Hematoma
A study testing embolization of the middle meningeal artery in people with Chronic Subdural Hematomas, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Chronic Subdural Hematomas
- What is being tested?
- embolization of the middle meningeal artery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 1 siteNetherlands
- Study dates
- 10 Dec 2020to 1 Oct 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- · CT-confirmed diagnosis of chronic Subdural Hematoma;
- Primary surgical treatment based on clinical symptoms (progressive neurological deficits).
Who cannot join
- · 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;
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam university medical Centers
Amsterdam, 1100 DD
About this study
Official title: Improving the Outcome of Chronic Subdural Hematoma by Embolization of Middle Meningeal Artery (ELIMINATE)
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).
Read more
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.
Read the 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.
- Conditions
- Chronic Subdural Hematomas
- Being tested
- embolization of the middle meningeal artery
- Medical subject headings
- Hematoma, Subdural, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
embolization of the middle meningeal arteryProcedure or surgery
The embolization procedure will be as follows: first femoral artery access will be obtained by using a 5 French micropuncture kit and common carotid and external carotid angiography is performed using a standard 5 French diagnostic catheter. A microcatheter is then advanced selectively under roadmap guidance into the middle meningeal artery (MMA), and MMA angiography is performed to evaluate for potential dangerous anastomoses such as the orbital branch to the ophthalmic artery. Embolization is performed using polyvinyl alcohol particles (100 microns in diameter) under blank fluoroscopic roadmap while carefully avoiding reflux. Particles are infused until lack of anterograde flow into the MMA branches is demonstrated on angiography, and the catheters are removed [31]. The procedure is performed under local anesthesia.
| Study group | Role | What they receive |
|---|---|---|
| Standard Care: burr hole surgery | No intervention | Patients who have had burr hole evacuation for symptomatic chronic subdural hematomas will be followed in the outpatient clinic after hospital discharge at 8, 16 and 24 weeks with a follow-up CT-scan of the head in addition to assessment of mRS, MOCA, mNIHSS, Markwalder score, SF-36, EQ-5D-5L, ALDS, iMCQ and iPCQ. |
| embolisation middle meningeal artery | Active comparator | Besides standard treatment those patient who are allotted to the intervention group will receive embolization of the middle meningeal artery until 72 hours after burr hole evacuation. After hospital discharge follow-up is at 8, 16 and 24 weeks with a follow-up CT-scan of the head in addition to assessment of mRS, MOCA, mNIHSS, Markwalder score, SF-36, EQ-5D-5L, ALDS, iMCQ and iPCQ. Receives: Procedure: embolization of the middle meningeal artery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reoperation
Number of patients who require a reoperation for recurrent cSDH
Measured: 8 weeks after discharge.
Reoperation
Number of patients who require a reoperation for recurrent cSDH
Measured: 16 weeks after discharge.
Reoperation
Number of patients who require a reoperation for recurrent cSDH
Measured: 24 weeks after discharge.
Secondary outcomes (24)
Hematoma volume reduction
hematoma volumes are measured on CT-scan of the head and compared to pre-operative volume
Measured: 8 weeks after discharge.
Hematoma volume reduction
hematoma volumes are measured on CT-scan of the head and compared to pre-operative volume
Measured: 16 weeks after discharge.
Hematoma volume reduction
hematoma volumes are measured on CT-scan of the head and compared to pre-operative volume
Measured: 24 weeks after discharge.
Complications
Number of complications will be monitored
Measured: 8 weeks after discharge.
Complications
Number of complications will be monitored
Measured: 16 weeks after discharge.
Complications
Number of complications will be monitored
Measured: 24 weeks after discharge.
modified National Institute Health Stroke Scale score
Neurological impairment measurement using mNIHSS; score 0 (no symptoms) to 31 (severe stroke)
Measured: 8 weeks after discharge.
modified National Institute Health Stroke Scale score
Neurological impairment measurement using mNIHSS; score 0 (no symptoms) to 31 (severe stroke)
Measured: 16 weeks after discharge.
modified Rankin Scale score
functional outcome measurement using mRS; score 0 (no symptoms) to 5 (severe handicap)
Measured: 24 weeks after discharge.
modified National Institute Health Stroke Scale score
Neurological impairment measurement using mNIHSS; score 0 (no symptoms) to 31 (severe stroke)
Measured: 24 weeks after discharge.
Montreal Cognitive Assessment
cognitive functioning measurement using MOCA; score 0 (severe deficit to 30 (no deficit)
Measured: 8 weeks after discharge.
Montreal Cognitive Assessment
cognitive functioning measurement using MOCA; score 0 (severe deficit to 30 (no deficit)
Measured: 16 weeks after discharge.
Montreal Cognitive Assessment
cognitive functioning measurement using MOCA; score 0 (severe deficit to 30 (no deficit)
Measured: 24 weeks after discharge.
mortality
mortality rate
Measured: 8 weeks after discharge.
mortality
mortality rate
Measured: 16 weeks after discharge.
mortality
mortality rate
Measured: 246 weeks after discharge.
Activities of Daily Living Scale
Assesses functional independence, generally in stroke patients; score 0 (totally dependent to 100 (completely independent)
Measured: at 24 weeks after discharge.
Short Form Health Survey
Quality of life measurement using a 36-item, patient-reported survey of patient health; consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: at 24 weeks after discharge.
EuroQol (EQ-5D-5L) questionnaire
Quality of life measurement:The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
Measured: at 24 weeks after discharge.
Medical Consumption questionnaire
Care- and health-related costs measurement using a generic instrument for measuring medical costs. The iMCQ includes questions related to frequently occurring contacts with health care providers and can be complemented with extra questions that are relevant for specific study populations.
Measured: at 24 weeks after discharge.
Productivity Cost Questionnaire
Care- and health-related costs measurement using a generic instrument for measuring medical costs
Measured: at 24 weeks after discharge.
Markwalder grading scale score
Neurological impairment measurement using the Markwalder grading scale; score 0 (neurologically normal) to 4 (Comatose with absent motor responses to painful stimuli, decerebrate or decorticate posturing)
Measured: at eight weeks after discharge
Markwalder grading scale score
Neurological impairment measurement using the Markwalder grading scale; score 0 (neurologically normal) to 4 (Comatose with absent motor responses to painful stimuli, decerebrate or decorticate posturing)
Measured: at 16 weeks after discharge
Markwalder grading scale score
Neurological impairment measurement using the Markwalder grading scale; score 0 (neurologically normal) to 4 (Comatose with absent motor responses to painful stimuli, decerebrate or decorticate posturing)
Measured: at 24 weeks after discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2020
- Study start10 Dec 2020
- Primary completion1 Jul 2025 (estimated)
- Study completion1 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (39)Papers the sponsor has linked to this study.
- Other trials for Chronic Subdural HematomasStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 170 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. dr. W.Peter Vandertop, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- William P. Vandertop, MD PhD, Study chair, Amsterdam Universities Medical Centers
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04511572
- Sponsor's protocol ID
- AMC Eliminate
- Acronym
- ELIMINATE
- Status last verified
- Jul 2024
- First submitted
- 7 Aug 2020
- Last updated
- 31 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Miah IP, Holl DC, Peul WC, Walchenbach R, Kruyt N, de Laat K, Koot RW, Volovici V, Dirven CMF, van Kooten F, Kho KH, den Hertog HM, van der Naalt J, Jacobs B, Groen RJM, Lingsma HF, Dammers R, Jellema K, van der Gaag NA; Dutch Subdural Hematoma Research Group (DSHR). Dexamethasone therapy versus surgery for chronic subdural haematoma (DECSA trial): study protocol for a randomised controlled trial. Trials. 2018 Oct 20;19(1):575. doi: 10.1186/s13063-018-2945-4.
PubMed 30342554Santarius T, Kirkpatrick PJ, Kolias AG, Hutchinson PJ. Working toward rational and evidence-based treatment of chronic subdural hematoma. Clin Neurosurg. 2010;57:112-22.
PubMed 21280503Sahyouni R, Goshtasbi K, Mahmoodi A, Tran DK, Chen JW. Chronic Subdural Hematoma: A Historical and Clinical Perspective. World Neurosurg. 2017 Dec;108:948-953. doi: 10.1016/j.wneu.2017.09.064. Epub 2017 Sep 19.
PubMed 28935548Yang W, Huang J. Chronic Subdural Hematoma: Epidemiology and Natural History. Neurosurg Clin N Am. 2017 Apr;28(2):205-210. doi: 10.1016/j.nec.2016.11.002. Epub 2017 Feb 1.
PubMed 28325454Holl DC, Volovici V, Dirven CMF, Peul WC, van Kooten F, Jellema K, van der Gaag NA, Miah IP, Kho KH, den Hertog HM, Lingsma HF, Dammers R; Dutch Chronic Subdural Hematoma Research Group (DSHR). Pathophysiology and Nonsurgical Treatment of Chronic Subdural Hematoma: From Past to Present to Future. World Neurosurg. 2018 Aug;116:402-411.e2. doi: 10.1016/j.wneu.2018.05.037. Epub 2018 May 14.
PubMed 29772364Edlmann E, Giorgi-Coll S, Whitfield PC, Carpenter KLH, Hutchinson PJ. Pathophysiology of chronic subdural haematoma: inflammation, angiogenesis and implications for pharmacotherapy. J Neuroinflammation. 2017 May 30;14(1):108. doi: 10.1186/s12974-017-0881-y.
PubMed 28558815Waqas M, Vakhari K, Weimer PV, Hashmi E, Davies JM, Siddiqui AH. Safety and Effectiveness of Embolization for Chronic Subdural Hematoma: Systematic Review and Case Series. World Neurosurg. 2019 Jun;126:228-236. doi: 10.1016/j.wneu.2019.02.208. Epub 2019 Mar 13.
PubMed 30878752Srivatsan A, Mohanty A, Nascimento FA, Hafeez MU, Srinivasan VM, Thomas A, Chen SR, Johnson JN, Kan P. Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: Meta-Analysis and Systematic Review. World Neurosurg. 2019 Feb;122:613-619. doi: 10.1016/j.wneu.2018.11.167. Epub 2018 Nov 24.
PubMed 30481628Court J, Touchette CJ, Iorio-Morin C, Westwick HJ, Belzile F, Effendi K. Embolization of the Middle meningeal artery in chronic subdural hematoma - A systematic review. Clin Neurol Neurosurg. 2019 Nov;186:105464. doi: 10.1016/j.clineuro.2019.105464. Epub 2019 Aug 10.
PubMed 31600604Sun TF, Boet R, Poon WS. Non-surgical primary treatment of chronic subdural haematoma: Preliminary results of using dexamethasone. Br J Neurosurg. 2005 Aug;19(4):327-33. doi: 10.1080/02688690500305332.
PubMed 16455539Soleman J, Nocera F, Mariani L. The conservative and pharmacological management of chronic subdural haematoma. Swiss Med Wkly. 2017 Jan 17;147:w14398. doi: 10.57187/smw.2017.14398. eCollection 2017.
PubMed 28102879Pang CH, Lee SE, Kim CH, Kim JE, Kang HS, Park CK, Paek SH, Kim CH, Jahng TA, Kim JW, Kim YH, Kim DG, Chung CK, Jung HW, Yoo H. Acute intracranial bleeding and recurrence after bur hole craniostomy for chronic subdural hematoma. J Neurosurg. 2015 Jul;123(1):65-74. doi: 10.3171/2014.12.JNS141189. Epub 2015 Feb 13.
PubMed 25679282Brennan PM, Kolias AG, Joannides AJ, Shapey J, Marcus HJ, Gregson BA, Grover PJ, Hutchinson PJ, Coulter IC; British Neurosurgical Trainee Research Collaborative. The management and outcome for patients with chronic subdural hematoma: a prospective, multicenter, observational cohort study in the United Kingdom. J Neurosurg. 2017 Oct;127(4):732-739. doi: 10.3171/2016.8.JNS16134. Epub 2016 Nov 11.
PubMed 27834599Ducruet AF, Grobelny BT, Zacharia BE, Hickman ZL, DeRosa PL, Andersen KN, Sussman E, Carpenter A, Connolly ES Jr. The surgical management of chronic subdural hematoma. Neurosurg Rev. 2012 Apr;35(2):155-69; discussion 169. doi: 10.1007/s10143-011-0349-y. Epub 2011 Sep 10.
PubMed 21909694Ban SP, Hwang G, Byoun HS, Kim T, Lee SU, Bang JS, Han JH, Kim CY, Kwon OK, Oh CW. Middle Meningeal Artery Embolization for Chronic Subdural Hematoma. Radiology. 2018 Mar;286(3):992-999. doi: 10.1148/radiol.2017170053. Epub 2017 Oct 10.
PubMed 29019449
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving the Outcome of Chronic Subdural Hematoma by Embolization of Middle Meningeal Artery (ELIMINATE)
- ClinicalTrials.gov ID
- NCT04511572
- Acronym / sponsor ID
- ELIMINATE / AMC Eliminate
- Conditions
- Chronic Subdural Hematomas
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 170 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- 10 Dec 2020 (actual)
- Primary completion
- 1 Jul 2025 (estimated)
- Study completion
- 1 Oct 2025 (estimated)
- First posted
- 13 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Care: burr hole surgery | No intervention | –Patients who have had burr hole evacuation for symptomatic chronic subdural hematomas will be followed in the outpatient clinic after hospital discharge at 8, 16 and 24 weeks with a follow-up CT-scan of the head in addition to assessment of mRS, MOCA, mNIHSS, Markwalder score, SF-36, EQ-5D-5L, ALDS, iMCQ and iPCQ. |
| embolisation middle meningeal artery | Active comparator | Procedure: embolization of the middle meningeal arteryBesides standard treatment those patient who are allotted to the intervention group will receive embolization of the middle meningeal artery until 72 hours after burr hole evacuation. After hospital discharge follow-up is at 8, 16 and 24 weeks with a follow-up CT-scan of the head in addition to assessment of mRS, MOCA, mNIHSS, Markwalder score, SF-36, EQ-5D-5L, ALDS, iMCQ and iPCQ. |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- · CT-confirmed diagnosis of chronic Subdural Hematoma;
Key exclusion criteria (4 listed)
- · Significant contraindication to angiography (eg. allergy for contrast);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| embolization of the middle meningeal arteryThe embolization procedure will be as follows: first femoral artery access will be obtained by using a 5 French micropuncture kit and common carotid and external carotid angiography is performed using a standard 5 French diagnostic catheter. A microcatheter is then advanced selectively under roadmap guidance into the middle meningeal artery (MMA), and MMA angiography is performed to evaluate for potential dangerous anastomoses such as the orbital branch to the ophthalmic artery. Embolization is performed using polyvinyl alcohol particles (100 microns in diameter) under blank fluoroscopic roadmap while carefully avoiding reflux. Particles are infused until lack of anterograde flow into the MMA branches is demonstrated on angiography, and the catheters are removed [31]. The procedure is performed under local anesthesia. | Procedure or surgery | embolisation middle meningeal artery |
Primary outcome
Reoperation
Time frame: 8 weeks after discharge.
Number of patients who require a reoperation for recurrent cSDH
Reoperation
Time frame: 16 weeks after discharge.
Number of patients who require a reoperation for recurrent cSDH
Reoperation
Time frame: 24 weeks after discharge.
Number of patients who require a reoperation for recurrent cSDH
24 secondary outcomes
Hematoma volume reduction
Time frame: 8 weeks after discharge.
Hematoma volume reduction
Time frame: 16 weeks after discharge.
Hematoma volume reduction
Time frame: 24 weeks after discharge.
Complications
Time frame: 8 weeks after discharge.
Complications
Time frame: 16 weeks after discharge.
Complications
Time frame: 24 weeks after discharge.
modified National Institute Health Stroke Scale score
Time frame: 8 weeks after discharge.
modified National Institute Health Stroke Scale score
Time frame: 16 weeks after discharge.
modified Rankin Scale score
Time frame: 24 weeks after discharge.
modified National Institute Health Stroke Scale score
Time frame: 24 weeks after discharge.
Montreal Cognitive Assessment
Time frame: 8 weeks after discharge.
Montreal Cognitive Assessment
Time frame: 16 weeks after discharge.
Montreal Cognitive Assessment
Time frame: 24 weeks after discharge.
mortality
Time frame: 8 weeks after discharge.
mortality
Time frame: 16 weeks after discharge.
mortality
Time frame: 246 weeks after discharge.
Activities of Daily Living Scale
Time frame: at 24 weeks after discharge.
Short Form Health Survey
Time frame: at 24 weeks after discharge.
EuroQol (EQ-5D-5L) questionnaire
Time frame: at 24 weeks after discharge.
Medical Consumption questionnaire
Time frame: at 24 weeks after discharge.
Productivity Cost Questionnaire
Time frame: at 24 weeks after discharge.
Markwalder grading scale score
Time frame: at eight weeks after discharge
Markwalder grading scale score
Time frame: at 16 weeks after discharge
Markwalder grading scale score
Time frame: at 24 weeks after discharge
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2024.
- Background: PubMed 30342554Miah IP, Holl DC, Peul WC, Walchenbach R, Kruyt N, de Laat K, Koot RW, Volovici V, Dirven CMF, van Kooten F, Kho KH, den Hertog HM, van der Naalt J, Jacobs B, Groen RJM, Lingsma HF, Dammers R, Jellema K, van der Gaag NA; Dutch Subdural Hematoma Research Group (DSHR). Dexamethasone therapy versus surgery for chronic subdural haematoma (DECSA trial): study protocol for a randomised controlled trial. Trials. 2018 Oct 20;19(1):575. doi: 10.1186/s13063-018-2945-4.
- Background: PubMed 21280503Santarius T, Kirkpatrick PJ, Kolias AG, Hutchinson PJ. Working toward rational and evidence-based treatment of chronic subdural hematoma. Clin Neurosurg. 2010;57:112-22.
- Background: PubMed 28935548Sahyouni R, Goshtasbi K, Mahmoodi A, Tran DK, Chen JW. Chronic Subdural Hematoma: A Historical and Clinical Perspective. World Neurosurg. 2017 Dec;108:948-953. doi: 10.1016/j.wneu.2017.09.064. Epub 2017 Sep 19.
- Background: PubMed 28325454Yang W, Huang J. Chronic Subdural Hematoma: Epidemiology and Natural History. Neurosurg Clin N Am. 2017 Apr;28(2):205-210. doi: 10.1016/j.nec.2016.11.002. Epub 2017 Feb 1.
- Background: PubMed 29772364Holl DC, Volovici V, Dirven CMF, Peul WC, van Kooten F, Jellema K, van der Gaag NA, Miah IP, Kho KH, den Hertog HM, Lingsma HF, Dammers R; Dutch Chronic Subdural Hematoma Research Group (DSHR). Pathophysiology and Nonsurgical Treatment of Chronic Subdural Hematoma: From Past to Present to Future. World Neurosurg. 2018 Aug;116:402-411.e2. doi: 10.1016/j.wneu.2018.05.037. Epub 2018 May 14.
- Background: PubMed 28558815Edlmann E, Giorgi-Coll S, Whitfield PC, Carpenter KLH, Hutchinson PJ. Pathophysiology of chronic subdural haematoma: inflammation, angiogenesis and implications for pharmacotherapy. J Neuroinflammation. 2017 May 30;14(1):108. doi: 10.1186/s12974-017-0881-y.
- Background: PubMed 30878752Waqas M, Vakhari K, Weimer PV, Hashmi E, Davies JM, Siddiqui AH. Safety and Effectiveness of Embolization for Chronic Subdural Hematoma: Systematic Review and Case Series. World Neurosurg. 2019 Jun;126:228-236. doi: 10.1016/j.wneu.2019.02.208. Epub 2019 Mar 13.
- Background: PubMed 30481628Srivatsan A, Mohanty A, Nascimento FA, Hafeez MU, Srinivasan VM, Thomas A, Chen SR, Johnson JN, Kan P. Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: Meta-Analysis and Systematic Review. World Neurosurg. 2019 Feb;122:613-619. doi: 10.1016/j.wneu.2018.11.167. Epub 2018 Nov 24.
- Background: PubMed 31600604Court J, Touchette CJ, Iorio-Morin C, Westwick HJ, Belzile F, Effendi K. Embolization of the Middle meningeal artery in chronic subdural hematoma - A systematic review. Clin Neurol Neurosurg. 2019 Nov;186:105464. doi: 10.1016/j.clineuro.2019.105464. Epub 2019 Aug 10.
- Background: PubMed 16455539Sun TF, Boet R, Poon WS. Non-surgical primary treatment of chronic subdural haematoma: Preliminary results of using dexamethasone. Br J Neurosurg. 2005 Aug;19(4):327-33. doi: 10.1080/02688690500305332.
- Background: PubMed 28102879Soleman J, Nocera F, Mariani L. The conservative and pharmacological management of chronic subdural haematoma. Swiss Med Wkly. 2017 Jan 17;147:w14398. doi: 10.57187/smw.2017.14398. eCollection 2017.
- Background: PubMed 25679282Pang CH, Lee SE, Kim CH, Kim JE, Kang HS, Park CK, Paek SH, Kim CH, Jahng TA, Kim JW, Kim YH, Kim DG, Chung CK, Jung HW, Yoo H. Acute intracranial bleeding and recurrence after bur hole craniostomy for chronic subdural hematoma. J Neurosurg. 2015 Jul;123(1):65-74. doi: 10.3171/2014.12.JNS141189. Epub 2015 Feb 13.
- Efficacy of Atorvastatin in Chronic Subdural Haematoma (REACH).Link provided by the sponsor.
- Tranexamic Acid to Prevent OpeRation in Chronic Subdural HematomaLink provided by the sponsor.
- Tocilizumab (RoActemra) and Tranexamic Acid (Cyklokapron) Used as Adjuncts to Chronic Subdural Hematoma Surgery.Link provided by the sponsor.
- Tranexamic Acid in the Treatment of Residual Chronic Subdural Hematoma (TRACE).Link provided by the sponsor.
- Treatment of Chronic Subdural Hematoma by Corticosteroids (SUCRE)Link provided by the sponsor.
- Guideline for economic evaluations in healthcareLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William P. Vandertop, MD PhD study chair
Amsterdam Universities Medical Centers
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing embolization of the middle meningeal artery in people with Chronic Subdural Hematomas, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 31 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dagmar Verbaan, PhD (+31205663316, d.verbaan@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reoperation (time frame: 8 weeks after discharge.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04511572, which also lists 39 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2024.