- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT07626671
Prospective MMA Embolization Registry (PRO-EMMA)
Prospective Outcomes of MMA Embolization: A Prospective Single-center Registry Investigating Endovascular Therapy for Chronic Subdural Hematomas
Chronic subdural hematoma (cSDH) is a common condition, particularly in older adults, that can substantially impair patients' quality of life, functional independence, and neurological well-being. Blood accumulates in the subdural space and persists due to the formation of a highly vascularized outer hematoma membrane. This membrane continuously rebleeds through fragile neovessels, driven in large part by branches of the middle meningeal artery (MMA), preventing spontaneous resolution and promoting hematoma growth. The standard treatment is surgical drainage, but recurrence rates reach up to 30%, largely because surgery does not address the underlying membrane vascularity. Middle meningeal artery embolization (MMAE) is a minimally invasive angiographic procedure that targets this root cause by occluding the arterial supply to the hematoma membrane, thereby reducing rebleeding and promoting resolution. Recent clinical trials and meta-analyses have demonstrated high efficacy and safety of MMAE, both as a standalone treatment and as an adjunct to surgery. Despite this evidence, standardized prospective data on patient selection, predictors of treatment success, and optimal follow-up are still lacking.
PRO-EMMA is a prospective, single-center registry at the Charité - Universitätsmedizin Berlin, a tertiary center consisting of three separate campuses. Pro-Emma systematically collects clinical, radiological, and procedural data from patients with cSDH who undergo MMAE. In addition to routine clinical care, participants undergo a structured follow-up protocol: CT scans within 7 days and at 3 months after the procedure, and standardized assessments of neurological status, functional outcome, and quality of life - using the Glasgow Coma Scale (GCS), Markwalder score, modified Rankin Scale (mRS), Glasgow Outcome Scale Extended (GOS-E), and EQ-5D-5L- before the procedure and at days 30, 90, and 120 post-intervention.
The study tests the hypothesis that MMAE leads to good functional outcomes, rapid hematoma resolution, and low recurrence rates, and that specific clinical, interventional, and imaging features predict treatment success. Findings will help identify which patients benefit most from MMAE, optimize treatment decisions, and establish a practical, evidence-based follow-up standard. The registry aims to enroll 75-150 patients over approximately 12 months.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Background and Rationale Chronic subdural hematoma (cSDH) is a common condition, particularly in older adults, that can substantially impair patients' quality of life, functional independence, and neurological well-being. Blood accumulates in the subdural space and persists due to the formation of a highly vascularized outer hematoma membrane, which continuously rebleeds through fragile neovessels driven in large part by branches of the middle meningeal artery (MMA). This prevents spontaneous resolution and promotes hematoma growth. The standard treatment is surgical drainage, but recurrence rates reach up to 30%. Middle meningeal artery embolization (MMAE) targets this root cause by occluding the arterial supply to the hematoma membrane. Recent randomized controlled trials and meta-analyses have demonstrated high efficacy and safety of MMAE, both as standalone treatment and as adjunct to surgery. However, prospective data with standardized, protocol-driven follow-up capturing radiological response, functional status, quality of life at pre-specified time points, and predictive clinical and imaging parameters remain scarce.
Study-Specific Follow-Up Protocol
The MMAE procedure is performed according to clinical routine and standard of care. Study-specific additions consist solely of structured follow-up assessments:
- Functional Outcome and quality-of-life assessments using GCS, Markwalder score, mRS, GOS-E, and EQ-5D-5L at baseline (pre-intervention) and at days 30, 90, and 120 post-intervention, conducted by structured telephone or in-person interview
- Imaging follow-up by cranial CT within 7 days and at 3 months post-intervention.
Treatment decisions are made exclusively on the basis of clinical indication and are independent of study participation.
Data Collection
Data are documented in pseudonymized case report forms. The following domains are recorded:
- Clinical: patient history, GCS, comorbidities, anticoagulation/antiplatelet therapy, symptom course
- Radiological: hematoma volume, architecture, laterality, localization, midline shift, MMA caliber, anatomical MMA variants, foramen spinosum diameter, surgery
- Procedural: embolic agent, technical details, distribution of embolic agent, degree of distal penetration, complications
- Clinical: mRS, GOS-E, EQ-5D-5L, Markwalder score at each time point; re-intervention, recurrence, mortality, symptom course
Data Management and Quality Assurance All participants are assigned a pseudonymized study ID. The assignment list is stored separately and encrypted, with access restricted to authorized study personnel only. Data are stored exclusively on Charité servers (clinical data: 10 years; CT imaging data: 30 years), in compliance with DSGVO, BlnDSG, and applicable federal data protection regulations.
Data entries are checked against predefined plausibility and range rules; inconsistencies or out-of-range values are flagged and resolved before analysis. Source data verification is performed by comparing CRF entries against medical records and imaging reports. Missing values are documented and reported in the statistical analysis but will not be imputed.
Statistical Analysis The study is exploratory. Data will be analyzed using descriptive statistics with 95% confidence intervals. Bivariate correlation analyses (Pearson or Spearman as appropriate) and logistic regression models will be used to identify predictors of treatment success. Potential confounders include patient age, anticoagulation status, hematoma architecture, and procedural variables. A sufficient events-per-variable (EPV) ratio will be ensured in all regression models.
Pre-specified Predictor Variables
The following baseline and procedural variables will be analyzed as potential predictors of radiological and clinical treatment outcome:
- Hematoma morphology on baseline cranial CT, classified according to Nakaguchi et al. (homogeneous, laminar, trabecular, or separated).
- Middle meningeal artery caliber, anatomical variants, and foramen spinosum diameter on baseline imaging.
- Presence and type of anticoagulation or antiplatelet therapy at time of intervention.
- Degree of distal MMA penetration of embolic agent and type of embolic agent used.
Risks and Burden The primary additional burden from study participation consists of: (1) radiation from up to two study-mandated CT scans (within 7 days and at 3 months post-intervention), performed within diagnostically acceptable dose ranges; and (2) minimal time investment for structured interviews at days 30, 90, and 120 (approximately 10-15 minutes each). No additional medical interventions or modifications to clinical care are introduced by study participation.
Undersøgelsestype
Tilmelding (Anslået)
Kontakter og lokationer
Studiekontakt
- Navn: Leonard Fetscher, MD
- Telefonnummer: +49 030 450 627 426
- E-mail: Leonard.fetscher@charite.de
Undersøgelse Kontakt Backup
- Navn: Jawed Nawabi, MD, MSc
- E-mail: jawed.nawabi@charite.de
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Prøveudtagningsmetode
Studiebefolkning
Beskrivelse
Inclusion Criteria:
- CT- or MRI-confirmed chronic subdural hematoma (cSDH)
- Planned or completed middle meningeal artery embolization (MMAE), either as primary treatment or as adjunct to surgical evacuation
- Age ≥ 18 years
- Modified Rankin Scale (mRS) ≤ 3 at baseline
- Written informed consent including agreement to structured follow-up (follow-up CT scans and clinical assessments)
- Willingness and ability to participate in structured follow-up assessments (telephone and/or in-person interviews)
Exclusion Criteria:
- Acute subdural hematoma requiring emergency neurosurgical intervention
- Missing or incomplete baseline clinical or radiological data
- Unavailability for prospective follow-up (e.g., no fixed address, no telephone contact)
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Kohorter og interventioner
Gruppe / kohorte |
Intervention / Behandling |
|---|---|
|
cSDH patients undergoing MMAE
Adult patients (≥18 years) with CT- or MRI-confirmed chronic subdural hematoma who undergo middle meningeal artery embolization (MMAE) as primary treatment or as an adjunct to surgical evacuation at the Charité - Universitätsmedizin Berlin.
|
Minimally invasive endovascular procedure in which the middle meningeal artery (MMA) is catheterized and occluded using approved embolic agents, performed as either primary treatment or adjunct to surgical evacuation for chronic subdural hematoma.
The procedure is performed according to clinical routine and standard of care; no modification of the clinical treatment is introduced by study participation.
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Hematoma volume reduction
Tidsramme: 3 months post-intervention
|
Percentage change in hematoma volume (mL) or thickness (mm) on cranial CT from baseline to 3-month follow-up.
Higher percentage reduction indicates better radiological response.
|
3 months post-intervention
|
|
Functional outcome (mRS)
Tidsramme: 90 days post-intervention
|
Functional status assessed by the modified Rankin Scale (mRS), a 7-point scale ranging from 0 (no symptoms) to 6 (death).
Higher scores indicate worse functional outcome.
Change from baseline to day 90 post-intervention.
|
90 days post-intervention
|
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Re-intervention rate
Tidsramme: 120 days post-intervention
|
Number of patients requiring any re-intervention, defined as repeat middle meningeal artery embolization or surgical rescue procedure, within 120 days post-intervention.
Higher numbers indicate worse outcome.
|
120 days post-intervention
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Quality of life (EQ-5D-5L)
Tidsramme: Baseline (pre-intervention), day 30, day 90, and day 120 post-intervention
|
Health-related quality of life assessed by the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) across five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each rated on a 5-point scale (1-5), plus a visual analogue scale (EQ-VAS, 0-100).
Lower dimension scores and higher EQ-VAS scores indicate better health status.
Compared to baseline pre-intervention.
|
Baseline (pre-intervention), day 30, day 90, and day 120 post-intervention
|
|
Extended functional outcome (GOS-E)
Tidsramme: Baseline (pre-intervention), day 30, day 90, and day 120 post-intervention
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Functional recovery assessed by the Glasgow Outcome Scale Extended (GOS-E), an 8-point scale ranging from 1 (death) to 8 (upper good recovery).
Higher scores indicate better functional outcome.
Compared to baseline pre-intervention.
|
Baseline (pre-intervention), day 30, day 90, and day 120 post-intervention
|
|
Neurological status (GCS)
Tidsramme: Baseline (pre-intervention), day 30, day 90, and day 120 post-intervention
|
Level of consciousness and neurological status assessed by the Glasgow Coma Scale (GCS), a 15-point scale (minimum 3, maximum 15) evaluating eye (1-4), verbal (1-5), and motor responses (1-6).
Higher scores indicate better neurological status.
Compared to baseline pre-intervention.
|
Baseline (pre-intervention), day 30, day 90, and day 120 post-intervention
|
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Symptom severity (Markwalder score)
Tidsramme: Baseline (pre-intervention), day 30, day 90, and day 120 post-intervention
|
cSDH-specific neurological grading assessed by the Markwalder Grading Scale (MGS), ranging from 0 (no neurological deficits) to 4 (comatose).
Lower scores indicate better neurological status.
Compared to baseline pre-intervention.
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Baseline (pre-intervention), day 30, day 90, and day 120 post-intervention
|
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Mortality
Tidsramme: 120 days post-intervention
|
Number of patients with all-cause mortality within 120 days post-intervention.
|
120 days post-intervention
|
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Treatment failure
Tidsramme: Day 90 post intervention
|
Number of patients with absent or insufficient hematoma resolution, defined as less than 50% reduction in hematoma volume on follow-up cranial CT compared to baseline.
Higher numbers indicate worse outcome.
|
Day 90 post intervention
|
Samarbejdspartnere og efterforskere
Efterforskere
- Ledende efterforsker: Jawed Nawabi, MD, MSc, Charite University, Berlin, Germany
Publikationer og nyttige links
Generelle publikationer
- Balser D, Farooq S, Mehmood T, Reyes M, Samadani U. Actual and projected incidence rates for chronic subdural hematomas in United States Veterans Administration and civilian populations. J Neurosurg. 2015 Nov;123(5):1209-15. doi: 10.3171/2014.9.JNS141550. Epub 2015 Mar 20.
- Nakaguchi H, Tanishima T, Yoshimasu N. Factors in the natural history of chronic subdural hematomas that influence their postoperative recurrence. J Neurosurg. 2001 Aug;95(2):256-62. doi: 10.3171/jns.2001.95.2.0256.
- Bartek J Jr, Sjavik K, Kristiansson H, Stahl F, Fornebo I, Forander P, Jakola AS. Predictors of Recurrence and Complications After Chronic Subdural Hematoma Surgery: A Population-Based Study. World Neurosurg. 2017 Oct;106:609-614. doi: 10.1016/j.wneu.2017.07.044. Epub 2017 Jul 19.
- Salem MM, Kuybu O, Nguyen Hoang A, Baig AA, Khorasanizadeh M, Baker C, Hunsaker JC, Mendez AA, Cortez G, Davies JM, Narayanan S, Cawley CM, Riina HA, Moore JM, Spiotta AM, Khalessi AA, Howard BM, Hanel R, Tanweer O, Levy EI, Grandhi R, Lang MJ, Siddiqui AH, Kan P, Ogilvy CS, Gross BA, Thomas AJ, Jankowitz BT, Burkhardt JK. Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: Predictors of Clinical and Radiographic Failure from 636 Embolizations. Radiology. 2023 May;307(4):e222045. doi: 10.1148/radiol.222045. Epub 2023 Apr 18.
- Gillespie CS, Veremu M, Cook WH, Ashraf M, Lee KS, Chedid Y, Alam AM, Karepov Y, Davies BM, Edlmann E, Papanagiotou P, Korfias S, Santarius T, Minett T, Hutchinson PJ, Kolias A. Middle meningeal artery embolization for chronic subdural hematoma: meta-analysis of three randomized controlled trials and review of ongoing trials. Acta Neurochir (Wien). 2025 Jun 10;167(1):166. doi: 10.1007/s00701-025-06587-4.
- Fiorella D, Monteith SJ, Hanel R, Atchie B, Boo S, McTaggart RA, Zauner A, Tjoumakaris S, Barbier C, Benitez R, Spelle L, Pierot L, Hirsch JA, Froehler M, Arthur AS; STEM Investigators. Embolization of the Middle Meningeal Artery for Chronic Subdural Hematoma. N Engl J Med. 2025 Feb 27;392(9):855-864. doi: 10.1056/NEJMoa2409845. Epub 2024 Nov 20.
- Liu J, Ni W, Zuo Q, Yang H, Peng Y, Lin Z, Li Z, Wang J, Zhen Y, Luo J, Lin Y, Chen J, Hua X, Lu H, Zhong M, Liu M, Zhang J, Wang Y, Wan J, Li Y, Li T, Mao G, Zhao W, Gao L, Li C, Chen E, Cheng X, Zhang P, Wang Z, Chen L, Zhang Y, Tian B, Shen F, Lei Y, Wu Y, Li Y, Duan G, Xu L, Lv N, Yu J, Xu X, Du Z, Zhang H, Hu J, Li Z, Yuan Q, Zhou Y, Wu G, Zhang L, Gao C, Dai D, Wu X, Zhang Y, Jiang H, Zhao R, Su J, Xu Y, Ospel JM, Majoie CBLM, Goyal M, Li Q, Yang P, Gu Y, Mao Y; MAGIC-MT Investigators. Middle Meningeal Artery Embolization for Nonacute Subdural Hematoma. N Engl J Med. 2024 Nov 21;391(20):1901-1912. doi: 10.1056/NEJMoa2401201.
- Davies JM, Knopman J, Mokin M, Hassan AE, Harbaugh RE, Khalessi A, Fiehler J, Gross BA, Grandhi R, Tarpley J, Sivakumar W, Bain M, Crowley RW, Link TW, Fraser JF, Levitt MR, Chen PR, Hanel RA, Bernard JD, Jumaa M, Youssef P, Cress MC, Chaudry MI, Shakir HJ, Lesley WS, Billingsley J, Jones J, Koch MJ, Paul AR, Mack WJ, Osbun JW, Dlouhy K, Grossberg JA, Kellner CP, Sahlein DH, Santarelli J, Schirmer CM, Singer J, Liu JJ, Majjhoo AQ, Wolfe T, Patel NV, Roark C, Siddiqui AH; EMBOLISE Investigators. Adjunctive Middle Meningeal Artery Embolization for Subdural Hematoma. N Engl J Med. 2024 Nov 21;391(20):1890-1900. doi: 10.1056/NEJMoa2313472.
Datoer for undersøgelser
Studer store datoer
Studiestart (Anslået)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Cerebrovaskulære lidelser
- Hjernesygdomme
- Sygdomme i centralnervesystemet
- Sygdomme i nervesystemet
- Karsygdomme
- Hjerte-kar-sygdomme
- Sår og skader
- Patologiske processer
- Kronisk sygdom
- Sygdomsegenskaber
- Blødning
- Kraniocerebralt traume
- Traumer, nervesystemet
- Intrakranielle blødninger
- Intrakraniel blødning, traumatisk
- Patologiske tilstande, tegn og symptomer
- Hæmatom, subdural
- Hæmatom
- Hæmatom, subdural, kronisk
Andre undersøgelses-id-numre
- EA1/248/25
Plan for individuelle deltagerdata (IPD)
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Kliniske forsøg med Kroniske subdurale hæmatomer
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Jules Bordet InstituteMacopharma; Belgian Hematological SocietyRekrutteringRefractory Chronic Graft Versus Host Disease (cGVHD)Belgien
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Icahn School of Medicine at Mount SinaiJohn Muir Health; Carondelet Neurological InstituteIkke rekrutterer endnuKronisk subdural blødning (CSDH)Forenede Stater
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Icahn School of Medicine at Mount SinaiMicroPort NeuroTech Co., Ltd.Ikke rekrutterer endnu
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Kwong Wah HospitalUkendtKronisk subduralt hæmatom | Subdural afløbKina
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University of ZurichStryker European Operations BVAfsluttetHæmatom, subdural, kronisk | Hæmatom, subduralt, intrakranielt | Hæmatom;Subdural;TraumatiskSchweiz
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Assiut UniversityIkke rekrutterer endnuKronisk ikke-traumatisk intrakraniel subdural blødning
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Integra LifeSciences CorporationMedtronic - MITGAfsluttetLækage af cerebrospinalvæske, subduralForenede Stater
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Beijing Tiantan HospitalRekrutteringKronisk subduralt hæmatomKina
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Microvention-Terumo, Inc.Ikke rekrutterer endnu
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University of RostockRekrutteringKroniske subdurale hæmatomerTyskland
Kliniske forsøg med Middle Meningeal Artery Embolization
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Weill Medical College of Cornell UniversityAfsluttetKronisk subduralt hæmatomForenede Stater
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The University of Texas Medical Branch, GalvestonNational Institute of Neurological Disorders and Stroke (NINDS)RekrutteringKronisk subduralt hæmatomForenede Stater
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Xinjiang Medical UniversityFirst Affiliated Hospital of Xinjiang Medical UniversityRekrutteringPrimær aldosteronisme | Suprarenalektomi | Super selektiv binyrearterie-emboliseringKina