MEMBRANE
Middle Meningeal Artery Embolization With n-Butyl Cyanoacrylate in Patients With Chronic Subdural Hematoma: A Randomized Clinical Trial
Clinical Question
Does middle meningeal artery embolization with n-BCA added to standard of care reduce hematoma recurrence/re-accumulation and need for surgery in chronic subdural hematoma?
Bottom Line
Adjunctive MMAE with n-BCA plus standard of care significantly reduced the rate of hematoma residual/re-accumulation or need for surgery at 6 months (11.6% vs 22.1%; OR 0.53; P = .04) compared with standard of care alone, without a significant increase in adverse events, supporting MMAE with n-BCA as an effective adjunctive treatment for symptomatic cSDH in both surgical and nonsurgical patients.
Major Points
- MMAE with n-BCA plus SOC reduced the primary effectiveness end point (residual or re-accumulation of hematoma >10 mm at 6 months or surgery on the cSDH within 6 months) to 11.6% (17/146) vs 22.1% (29/131) with SOC alone — final estimate of common OR 0.53 (90% CI, 0.31-0.91); P = .04 (47% reduction in odds)
- Adverse events through 6 months occurred in 71.8% (130/181) of MMAE plus SOC participants vs 65.3% (124/190) of SOC alone participants, with no significant increase attributable to MMAE
- MMAE plus SOC was noninferior to SOC alone for good functional outcome at 3 months as assessed by the modified Rankin Scale
- Both surgical (post-evacuation adjunct) and nonsurgical (adjunct to medical management) cohorts were enrolled and randomized 1:1, with no crossover to MMAE permitted during follow-up
- Operators were experienced (≥15 prior n-BCA cases and ≥5 prior MMAE cases required) and trained to attempt distal penetration of the embolic agent
Design
Study Type: Prospective, multicenter, open-label, randomized clinical trial
Randomization: 1
Blinding: Open-label; end points adjudicated by an independent imaging core laboratory and clinical events committee; mRS and MGS at 3, 6, and 12 months collected independently
Allocation: 1:1 randomization to MMAE plus standard of care or standard of care alone, within surgical and nonsurgical cohorts determined by site physicians
Enrollment Period: May 27, 2021, to February 6, 2024
Follow-up Duration: Follow-up at 1, 3, 6, and 12 months; results reported through 6 months
Centers: 30
Countries: United States, China
Sample Size: 376
Analyzed: 277
Analysis: Primary effectiveness: intention-to-treat; primary safety: as-treated
Registration: ClinicalTrials.gov NCT04816591
Inclusion Criteria
- Age 18 to 90 years
- Diagnosis of chronic subdural hematoma with mass effect on brain imaging (CT or MRI) with correlated clinical symptoms
- Symptomatic cSDH previously untreated and not requiring emergent surgery or decompression
- Prerandomization modified Rankin Scale score of 3 or less
- Nonsurgical cohort: midline shift <10 mm and hematoma thickness >10 mm at screening (no size requirement for surgical patients)
- Treatment with the study device considered feasible in the opinion of the treating physician
Arms
| Field | MMAE plus standard of care | Control |
|---|---|---|
| N | 188 | 188 |
| Intervention | Middle meningeal artery embolization with TRUFILL n-BCA liquid embolic system (n-BCA, ethiodized oil, tantalum powder) plus standard of care; surgical cohort: MMAE within 10 days after surgical evacuation during the same admission; nonsurgical cohort: MMAE within 10 days after randomization plus nonsurgical medical management | Surgical cohort: surgical evacuation alone with no further intervention; nonsurgical cohort: nonsurgical medical management alone (modifying/stopping anticoagulation, initiating statins, observation, repeat imaging, lifestyle modification); no crossover to MMAE permitted |
| Duration | Single embolization procedure; follow-up through 6 months (12 months planned) | Follow-up through 6 months (12 months planned) |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Residual or re-accumulation of hematoma (>10 mm, assessed by independent core laboratory) at 6 months or requiring a surgical procedure on the cSDH within 6 months (intention-to-treat) | Primary | 29/131 (22.1%) | 17/146 (11.6%) | 0.53 | P = .04 |
| Good functional outcome at 3 months assessed by modified Rankin Scale (noninferiority analysis) | Secondary | MMAE plus standard of care was noninferior to standard of care alone | |||
| Incidence of adverse events through 6 months (primary safety end point, as-treated analysis) | Safety | MMAE plus SOC: 130/181 (71.8%) · SOC alone: 124/190 (65.3%) · No significant increase in adverse events with MMAE plus standard of care | |||
| Any adverse event through 6 months | Adverse | MMAE plus SOC 130/181 (71.8%) vs SOC alone 124/190 (65.3%) | |||
Criticisms
- Open-label design, although end points were adjudicated by an independent core laboratory and clinical events committee
- Primary effectiveness reported with a 90% CI rather than the conventional 95% CI
- Sponsor (Johnson & Johnson MedTech) managed data collection, monitoring, and performed all statistical analyses
- The article was corrected on August 10, 2026, for errors in the Results, Discussion, Figure 2, and Table 2
- 12-month results not yet reported in this publication
Funding
Johnson & Johnson MedTech; the sponsor was involved in study design and conduct, data collection/management/analysis and interpretation, manuscript preparation, and the decision to submit for publication; all analyses for publication were performed by the study statistician at Johnson & Johnson MedTech
Based on: MEMBRANE (JAMA Neurology, 2026)
Authors: Christopher P Kellner, Ansaar T Rai, Hazem Shoirah, ..., for the MEMBRANE Study Group
Citation: JAMA Neurol. 2026 Jun 15;83(8):749-758. doi: 10.1001/jamaneurol.2026.1542
Content summarized and formatted by NeuroTrials.ai.