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MEMBRANE

Middle Meningeal Artery Embolization with n-Butyl Cyanoacrylate for the Treatment of Subdural Hematomas: The MEMBRANE Study Design

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Year of Publication: 2025

Authors: Kellner CP, Al-Mufti F, Gupta R, ..., Rai AT

Journal: Stroke: Vascular and Interventional Neurology

Citation: Stroke Vasc Interv Neurol. 2025;5:e001828. DOI: 10.1161/SVIN.125.001828

Link: https://doi.org/10.1161/SVIN.125.001828

Clinical Question

Is TRUFILL n-butyl cyanoacrylate middle meningeal artery embolization, added to standard-of-care, safe and effective in reducing residual/re-accumulation or reoperation for chronic subdural hematoma compared with standard-of-care alone?

Bottom Line

This is a study design/protocol publication; no outcome results are reported. The MEMBRANE trial will provide pivotal evidence on TRUFILL n-BCA MMA embolization as a primary or adjunctive treatment for cSDH, with results expected in 2025.

Major Points

  • Protocol/design paper for the MEMBRANE trial (NCT04816591); no efficacy/safety results reported.
  • Prospective, multicenter, open-label, randomized-controlled trial enrolling ~376 adults at ~35 sites in the US and China.
  • Participants first allocated to surgical or nonsurgical cohort by treating physician, then randomized 1:1 within each cohort to TRUFILL n-BCA MMA embolization + SOC vs SOC alone.
  • No treatment-arm crossover permitted; follow-up CT scans and visits at 1, 3, 6, and 12 months.
  • Primary effectiveness endpoint: residual or re-accumulation of hematoma >10 mm at 6 months (independent imaging core lab) or reoperation/surgical procedure on the hematoma within 6 months.
  • Primary safety endpoint: occurrence of all adverse events through 6 months.
  • Enrollment occurred May 2021 to February 2024; trial completion expected in 2025.
  • Background literature suggests MMA embolization may reduce recurrence to 2–3% vs 11% with surgery and 17% with pharmacotherapy.

Design

Study Type: Prospective, multicenter, open-label, randomized-controlled trial (study design/protocol publication)

Randomization: 1

Blinding: Open-label (independent imaging core laboratory assesses primary effectiveness endpoint; blinded independent evaluators assess mRS and Markwalder Grading Scale)

Allocation: 1:1 randomization within surgical and nonsurgical cohorts to TRUFILL n-BCA MMA embolization + SOC vs SOC alone; no crossover

Enrollment Period: May 2021 to February 2024

Follow-up Duration: 12 months (visits at 1, 3, 6, and 12 months post procedure)

Centers: 35

Countries: United States, China

Sample Size: 376

Analyzed: 0

Analysis: Cochran–Mantel–Haenszel statistics stratified by surgery to test superiority of SOC + TRUFILL n-BCA embolization over SOC alone in the primary effectiveness endpoint. Intent-to-treat analysis set for primary effectiveness; considered successful if 1-sided P value from continuity-corrected Cochran–Mantel–Haenszel test is <0.05. Secondary endpoints tested sequentially at 1-sided 0.05 significance using a gatekeeping strategy contingent on primary success. Missing primary data handled with multiple imputation; sensitivity analyses use per-protocol and as-treated sets. Gail–Simon test at alpha 0.15 for qualitative interaction between the two cohorts. Prespecified subgroup analyses on clinically meaningful risk factors.

Power Calculation: Assuming a common odds ratio of 0.34, a sample size of 376 participants, after accounting for 10% attrition, will provide ≥80% power for the primary effectiveness endpoint at a 1-sided significance level of 0.05. Anticipated event rates derived from prior literature. For the primary safety endpoint, ≥80% probability of observing AEs occurring at ≥1% incidence within each treatment group.

Registration: NCT04816591

Inclusion Criteria

  • Age 18 to 90 years
  • Diagnosed with chronic subdural hematoma (cSDH) with mass effect and correlated clinical symptoms
  • Modified Rankin Scale (mRS) score ≤3
  • Demonstrated stability of the hematoma on imaging
  • Capable of providing informed consent or having a legally authorized representative provide consent
  • Treatment with TRUFILL n-BCA considered technically feasible by the treating physician
  • Nonsurgical cohort only: cSDH midline shift <10 mm and thickness >10 mm

Exclusion Criteria

  • Full exclusion criteria provided in Supplementary Table S1 (not detailed in the available source text)

Arms

FieldTRUFILL n-BCA MMA embolization + SOC (surgical cohort)ControlTRUFILL n-BCA MMA embolization + SOC (nonsurgical cohort)Control
N
InterventionStandard-of-care surgical management (burr hole or craniotomy) plus MMA embolization with TRUFILL n-butyl cyanoacrylate Liquid Embolic System ≤10 days after surgery, delivered via microcatheter under fluoroscopic guidanceStandard-of-care surgical management of cSDH without MMA embolization; no crossover to embolization permittedStandard-of-care nonsurgical/medical management (anticoagulant modification, statins, observation, repeat imaging, lifestyle modification) plus MMA embolization with TRUFILL n-BCA ≤10 days after randomizationStandard-of-care nonsurgical/medical management without MMA embolization; no crossover permitted
DurationSingle procedure with 12-month follow-up12-month follow-upSingle procedure with 12-month follow-up12-month follow-up

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Primary effectiveness: residual or re-accumulation of hematoma (>10 mm) at 6 months assessed by independent imaging core laboratory, OR reoperation/surgical procedure on the hematoma within 6 months after randomization. Primary safety: occurrence of all adverse events through 6 months.PrimaryTime Point: 6 months
Effectiveness — Mean change in hematoma volume at 3 and 12 months compared with baseline (independent imaging core lab)Secondary
Effectiveness — Reduction of >50% in hematoma volume at 3, 6, and 12 months (independent imaging core lab)Secondary
Effectiveness — Complete resolution of the cSDH at 3, 6, and 12 months (independent imaging core lab)Secondary
Effectiveness — Median time to achieve complete resolution of the cSDH (time by study site; resolution by core lab)Secondary
Effectiveness — Participants who develop an acute component of existing cSDH or a new cSDH at 3, 6, and 12 months (independent imaging core lab)Secondary
Effectiveness — Participants requiring a surgical procedure on the cSDH within 3 and 6 months after randomization (study site)Secondary
Effectiveness — Patients requiring >1 surgery on the cSDH within 3, 6, and 12 months after randomization (study site)Secondary
Gatekeeping-tested (sequential order) — Good functional outcome at 3 months (mRS 0–2, or no worsening from baseline if baseline mRS ≥3; blinded independent evaluator)Secondary
Gatekeeping-tested — Participants requiring a surgical procedure on the cSDH within 12 months (study site)Secondary
Gatekeeping-tested — Mean change in hematoma volume at 6 months compared with baseline (independent imaging core lab)Secondary
Health economics — Hospital days and intensive care unit days (study site)Secondary
Health economics — Change in EuroQol 5-dimension, 5-level score at 6 months compared with baseline (study site)Secondary
Occurrence of all adverse events through 6 months (primary safety endpoint)Safety
mRS score distribution change at 3, 6, and 12 months (blinded independent evaluator)Safety
Death, stroke, myocardial infarction, or thromboembolic complications within 3, 6, and 12 months (clinical events committee)Safety
Development of new-onset seizures within 3, 6, and 12 months (clinical events committee)Safety
Change in Markwalder Grading Scale at 3, 6, and 12 months compared with baseline (blinded independent evaluator)Safety
Change in Mini-Mental State Examination score at 6 months compared with baseline (study site)Safety

Subgroup Analysis

Pre-specified cohorts: surgical vs nonsurgical management, with separate randomization within each cohort. Gail–Simon test (alpha 0.15) for qualitative interaction between cohorts; primary effectiveness endpoint also analyzed by clinically meaningful risk-factor subgroups.

Criticisms

  • Open-label design (no patient/physician blinding), although primary imaging endpoint is adjudicated by independent core lab.
  • Allocation to surgical vs nonsurgical cohort determined by site physician (not randomized), introducing potential selection bias between cohorts.
  • No data yet — this is a design paper; safety and efficacy conclusions await trial completion in 2025.
  • Generalizability limited to sites in the US and China.
  • Sponsor (Cerenovus/Johnson & Johnson MedTech) was involved in study concept/design, writing of the report, and decision to submit.

Funding

This study is funded by Cerenovus, part of Johnson & Johnson MedTech (Irvine, CA, USA). Medical writing support was provided by Michelle Hughes, BSc (Hons), of Lumanity Communications Inc., funded by Cerenovus. The sponsor was involved in the concept and design of the study, writing of the report, and the decision to submit for publication.

Based on: MEMBRANE (Stroke: Vascular and Interventional Neurology, 2025)

Authors: Kellner CP, Al-Mufti F, Gupta R, ..., Rai AT

Citation: Stroke Vasc Interv Neurol. 2025;5:e001828. DOI: 10.1161/SVIN.125.001828

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