Middle Meningeal Artery Embolization for the Treatment of Subdural Hematomas With TRUFILL® n-BCA (MEMBRANE)

This is a prospective, multi-center, open-label, randomized controlled study in which subjects can receive standard of care (SOC) alone or SOC and TRUFILL n-BCA MMA embolization for the treatment of chronic subdural hematomas (cSDH).

Study Overview

• Status: Completed
• Conditions: Chronic Subdural Hematoma
• Intervention / Treatment: Device: Experimental: Interventional Cohort: TRUFILL n-Butyl Cyanoacrylate (n-BCA) Liquid Embolic System; Other: Standard of Care Surgery; Device: Experimental: Interventional Cohort: TRUFILL n-BCA Liquid Embolic System; Other: Standard of Care Medical Management

Detailed Description

This is a prospective, multi-center, open-label, randomized controlled study in which up to 376 subjects will be randomized to receive standard of care (SOC) alone or SOC and TRUFILL n-BCA MMA embolization for the treatment of cSDH.

• Study Type: Interventional
• Enrollment (Actual): 376
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Nanjing, China, 210008
    • Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
  • Shanghai, China, 200127
    • Renji Hospital, Shanghai Jiaotong University School of Medicine
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85710
      • Carondelet St Joseph's Hospital
  • California
    • Walnut Creek, California, United States, 94598
      • John Muir Physician Network Clinical Research Center
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06032
      • Hartford Hospital
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • George Washington University
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist Medical Center
    • Miami, Florida, United States, 33136
      • University of Miami - Jackson Memorial Hospital
    • Orlando, Florida, United States, 32803
      • Advent Health Orlando
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Marietta, Georgia, United States, 30067
      • Wellstar Health System
    • Savannah, Georgia, United States, 31405
      • Memorial Health University Health Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Burlington, Massachusetts, United States, 02115
      • Lahey Hospital & Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • Valhalla, New York, United States, 10595
      • Westchester Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Columbus, Ohio, United States, 43214
      • Ohio Health
    • Toledo, Ohio, United States, 43608
      • Mercy Health St Vincent Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital of Research
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Semmes Murphey Foundation
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Plano, Texas, United States, 75075
      • Texas Stroke Institute
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia School of Medicine
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pre-randomization mRS </= 3
• Confirmed diagnosis of chronic subdural hematoma
• Completed informed consent

Exclusion Criteria:

• Acute subdural hematoma
• Prior treatment of target subdural hematoma
• Markwalder assessment >/= 3
• Glasgow Coma Scale < 9
• Presumed microbial superinfection
• CT or MRI evidence of intracranial tumor or mass lesion
• Life expectancy < 1 year
• Women who are pregnant, lactating, or who are of childbearing age and plan on becoming pregnant during the study
• Current involvement in another clinical trial that may confound study endpoints

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Interventional Cohort: Treatment Arm; Standard of Care Surgery + Embolization	Device: Experimental: Interventional Cohort: TRUFILL n-Butyl Cyanoacrylate (n-BCA) Liquid Embolic System; Standard of Care Surgery + Embolization
Active Comparator: Standard of Care Surgery Only	Other: Standard of Care Surgery; Standard of Care Surgery Only
Experimental: Interventional Cohort: Treatment Arm; Standard of Care Medical Management + Embolization	Device: Experimental: Interventional Cohort: TRUFILL n-BCA Liquid Embolic System; Standard of Care Medical Management + Embolization
Active Comparator: Standard of Care Medical Management Only; Standard of Care medical management only.	Other: Standard of Care Medical Management; Standard of Care Medical Management Only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Residual or Re-accumulation of the Chronic Subdural Hematoma (cSDH) (Greater Than [>] 10 Millimeter [mm]) as Assessed by an Independent Core Laboratory OR Any Re-operation or Surgical Procedure on the cSDH at 6 Months	Percentage of participants and odds ratio (OR) of participants with residual or re-accumulation of the cSDH (>10 mm) at 6 months as assessed by an independent core laboratory or re-operation or surgical procedure on the cSDH at 6 months post-randomization in the treatment with eMMA vs. standard of care is represented. Residual or re-accumulation of the cSDH >10 mm was a threshold included in the guidelines for surgical evacuation and was considered to be of prognostic importance given its association with mortality, decreased quality of life, and complications from new or repeat procedures.	At 6 months
Percentage of Participants With All Adverse Events (AEs)	An AE was any untoward medical experience (sign, symptom, illness, abnormal laboratory value, or other medical event) occurring to a participant during the course of the study whether or not related to the investigational device. SAE was any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, was life-threatening experience, a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. All AEs including both serious and non serious were reported.	From randomization up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Good Functional Outcome at 3 Months (Modified Rankin Score [mRS] 0-2 or no Worsening From Baseline if Baseline mRS Greater Than Equal to [>=] 3)	Participants were considered to have a good functional outcome if the 3-month mRS was less than or equal to (<=) 2 or otherwise no worsening from baseline mRS if the baseline mRS was >=3. mRS was used to assess the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scales ranges from 0-6, as follows: 0 = No symptoms; 1 = No significant disability. Able to carry out all usual activities, despite some symptoms; 2 = Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities; 3 = Moderate disability. Requires some help, but able to walk unassisted; 4 = Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted; 5 = Severe disability. Requires constant nursing care and attention, bedridden, incontinent; 6 = Dead; higher values reflecting more severe disability or death.	At Month 3
Number of Participants With Shift From Baseline in Mini-Mental State Exam (MMSE) Score at 6 Months	MMSE was a standardized tool to assess mental state in elderly patients. It included tests of orientation, attention, memory, language, and visual-spatial skills. It is comprised of questions (For example (e.g.), "What is the year?") and tasks (e.g., "Make up and write a sentence about anything"). MMSE scores range between 0 and 30. Scores 0-17 indicated severe cognitive impairment, scores 18-23 indicated mild impairment, and scores 24-30 were considered normal. Higher scores indicated better cognitive function. Baseline was defined as the last non-missing measurement collected prior to randomization.	Baseline, 6 months
Hospital Days and Intensive Care Unit (ICU) Days	Hospital days included total length of stay in hospital (including ICU) for index procedure. ICU days included length of stay at ICU during hospitalizations for index procedure.	From randomization up to 6 months
Change From Baseline in EuroQol-5 Dimension-5 Levels (EQ-5D-5L) Score at 6 Months	The EQ-5D-5L measured self-assessed health-related quality of life based on five categories: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each area was rated on a scale that described the degree of problems in that area (that is (i.e.)., "I had no problems walking about," "slight problems," "moderate problems," "severe problems," or "unable to walk"). This tool also had an overall health scale ranged from 1 to 100 to describe the condition of their health, 100 being the best imaginable. Higher scores indicating better QoL. Baseline was defined as the last non-missing measurement collected prior to randomization.	Baseline, Month 6
Change From Baseline in Hematoma Volume at 3, 6 and 12 Months, as Assessed by an Independent Core Laboratory	Hematoma volume was assessed by independent core laboratory. An independent imaging core laboratory was utilized to provide an unbiased and standardized assessment of study imaging. Hematoma volume was calculated using the ABC/2 method (multiplying Diameters A, B, and C and dividing by 2), where Diameter A was defined as the largest length in the axial plane to each corner of the SDH, Diameter B was defined as the maximum with 90 degree to Diameter A in the same slice, Diameter C was defined as the maximum height of the hematoma. For the calculation of the height, the number of slices with visible hematoma was multiplied by the thickness of the CT-scan. Change from baseline was defined as: post-baseline value minus baseline value, with negative values indicating improvement with respect to baseline (a reduction in hematoma volume). Baseline was defined as the last non-missing measurement collected prior to randomization.	Baseline, Months 3, 6 and 12
Number of Participants With Greater Than (>) 50 Percent (%) Reduction in Hematoma Volume at 3, 6, and 12 Months as Assessed by an Independent Core Laboratory	Hematoma volume was assessed by independent core laboratory. An independent imaging core laboratory was utilized to provide an unbiased and standardized assessment of study imaging. Hematoma volume was calculated using the ABC/2 method (multiplying Diameters A, B, and C and dividing by 2), where Diameter A was defined as the largest length in the axial plane to each corner of the SDH, Diameter B was defined as the maximum with 90 degree to Diameter A in the same slice, Diameter C was defined as the maximum height of the hematoma. For the calculation of the height, the number of slices with visible hematoma was multiplied by the thickness of the CT-scan. Hematoma volume reduction (%) was calculated as: (post-baseline hematoma volume minus baseline volume) divided by baseline volume *100%. A reduction >50% was defined as a decrease in hematoma volume of more than half compared with baseline. Baseline was defined as the last non-missing measurement collected prior to randomization.	Month 3, Month 6 and Month 12
Number of Participants With Complete Resolution of the cSDH at 3, 6, and 12 Months as Assessed by an Independent Core Laboratory	Number of participants with complete resolution of the cSDH at 3, 6, and 12 months as assessed by an independent core laboratory was reported. Complete resolution was defined as the absence of measurable cSDH on CT imaging, with no residual collection visible on the evaluated slices.	At Months 3, 6 and 12
Median Time to Achieve Complete Resolution of the cSDH	Median time to achieve complete resolution was estimated as the time point corresponding to a 50% probability of resolution of the cSDH based on the core laboratory evaluations. cSDH was evaluated using CT imaging reviewed by an independent blinded core laboratory. Complete resolution was defined as the absence of measurable cSDH on CT imaging. Time to complete resolution was calculated as the number of days from baseline to the first imaging assessment demonstrating complete resolution.	From baseline up to Month 12
Percentage of Participants Who Developed an Acute Component of Their Existing cSDH or a New cSDH (Kaplan-Meier Estimate) at 3, 6, and 12 Months as Assessed by an Independent Core Laboratory	Percentage of participants who developed an acute component of their existing cSDH or a new cSDH at 3, 6, and 12 months as assessed by an independent core laboratory was reported. The first incidence of an acute component of an existing cSDH or a new cSDH was considered as event. Percentages reported are Kaplan-Meier estimates of cumulative incidence.	At Months 3, 6, and 12
Percentage of Participants Who Required a Surgical Procedure on the cSDH (Kaplan-Meier Estimate) Within 3 and 6 Months Post-Randomization	Participants who underwent re-operation or surgical procedure on the cSDH within 3 and 6 months post randomization were reported. Percentages reported are Kaplan-Meier estimates of cumulative incidence.	From randomization up to Months 3 and 6
Number of Participants Who Required More Than One Surgical Procedure on the cSDH Within 3, 6, and 12 Months Post-Randomization	Number of participants who required more than one surgical procedure on the cSDH within 3, 6, and 12 months post-randomization were reported.	From randomization up to Months 3, 6 and 12
Number of Participants Who Required a Surgical Procedure on the cSDH Within 12 Months	Number of participants who required a surgical procedure on the cSDH within 12 months were reported.	From randomization up to Month 12
Number of Participants With Shift From Baseline in Modified Rankin Scale (mRS) Score at 3, 6, and 12 Months	mRS was used to assess the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scales ranges from 0-6, as follows: 0 = No symptoms; 1 = No significant disability. Able to carry out all usual activities, despite some symptoms; 2 = Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities; 3 = Moderate disability. Requires some help, but able to walk unassisted; 4 = Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted; 5 = Severe disability. Requires constant nursing care and attention, bedridden, incontinent; 6 = Dead; higher values reflecting more severe disability or death. Baseline was defined as the last non-missing measurement collected prior to randomization.	Baseline, Months 3, 6 and 12
Number of Participants With Death, Stroke, Myocardial Infarction (MI) or Thromboembolic Complications Within 6 and 12 Months as Assessed by the Clinical Events Committee (CEC)	Number of participants with death, stroke, MI or thromboembolic complications within 6 and 12 months as assessed by the CEC were reported.	From randomization up to Months 6 and 12
Percentage of Participants With New Onset of Seizures (Kaplan-Meier Estimate) Within 3, 6, and 12 Months as Assessed by the Clinical Events Committee (CEC)	Percentage of participants with new onset of seizures within 3, 6, and 12 months as assessed by the CEC were reported. Percentages reported are Kaplan-Meier estimates of cumulative incidence.	From randomization up to Months 3, 6, and 12
Number of Participants With Shift From Baseline in Markwalder Neurological Grading Scale (MGS) at 3, 6, and 12 Months	Number of participants with shift from baseline in MGS at 3, 6, and 12 months was reported. The MGS is a grading system developed to evaluate neurological performance in patients with cSDH. MGS is a 5 point scale ranging from 0 to 4, where lower scores indicate less neurological impairment and higher scores indicate greater impairment. The scale is defined as follows: Grade 0: patient neurologically normal; Grade 1: patient alert and oriented with mild symptoms such as headache or mild neurologic deficit; Grade 2: patient drowsy or disoriented with variable neurologic deficit; Grade 3: patient stuporous but responsive to noxious stimuli with focal neurologic signs; and Grade 4: patient comatose with absent motor response to painful stimuli. Baseline was defined as the last non-missing measurement collected prior to randomization.	Baseline, Months 3, 6 and 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health Economics	Hospital days	365 days post procedure

Collaborators and Investigators

• Sponsor: Cerenovus, Part of DePuy Synthes Products, Inc.
• Investigators: Principal Investigator: Christopher Kellner, MD, Mount Sinai Hospital; Principal Investigator: Ansaar Rai, MD, West Virginia University

Publications and helpful links

General Publications

• Kellner CP, Al-Mufti F, Gupta R, Jankowitz BT, Starke RM, Rai AT. Middle Meningeal Artery Embolization with n-Butyl Cyanoacrylate for the Treatment of Subdural Hematomas: The MEMBRANE Study Design. Stroke Vasc Interv Neurol. 2025 Sep 17;5(6):e001828. doi: 10.1161/SVIN.125.001828. eCollection 2025 Nov.

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2021
• Primary Completion (Actual): August 15, 2024
• Study Completion (Actual): March 26, 2025

Study Registration Dates

• First Submitted: March 23, 2021
• First Submitted That Met QC Criteria: March 23, 2021
• First Posted (Actual): March 25, 2021

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Chronic Subdural Hematoma, MMA Embolization
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Chronic Disease; Disease Attributes; Hemorrhage; Craniocerebral Trauma; Trauma, Nervous System; Intracranial Hemorrhages; Intracranial Hemorrhage, Traumatic; Pathological Conditions, Signs and Symptoms; Hematoma, Subdural; Hematoma; Hematoma, Subdural, Chronic
• Other Study ID Numbers: CNV_2020_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Johnson & Johnson Medical Device Companies have an agreement with the Yale Open Data Access (YODA) Project to serve as the independent review panel for evaluation of requests for clinical study reports and participant level data from investigators and physicians for scientific research that will advance medical knowledge and public health. Requests for access to the study data can be submitted through the YODA Project site at http://yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No