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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)

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

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

Field	TRUFILL n-BCA MMA embolization + SOC (surgical cohort)	Control	TRUFILL n-BCA MMA embolization + SOC (nonsurgical cohort)	Control
N	0	0	0	0
Intervention	Standard-of-care surgical management plus MMA embolization with TRUFILL n-butyl cyanoacrylate Liquid Embolic System ≤10 days after surgery, delivered via microcatheter under fluoroscopic guidance	Standard-of-care surgical management of cSDH without MMA embolization; no crossover to embolization permitted	Standard-of-care nonsurgical/medical management (anticoagulant modification, statins, observation, repeat imaging, lifestyle modification) plus MMA embolization with TRUFILL n-BCA ≤10 days after randomization	Standard-of-care nonsurgical/medical management without MMA embolization; no crossover permitted
Duration	Single procedure with 12-month follow-up	12-month follow-up	Single procedure with 12-month follow-up	12-month follow-up

Outcomes

Outcome	Type	Control
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. Primary safety: occurrence of all adverse events through 6 months.	Primary	Time Point: 6 months
Good functional outcome at 3 months (mRS 0–2, or no worsening from baseline if baseline mRS ≥3)	Secondary
Change in hematoma volume	Secondary
Complete cSDH resolution	Secondary
Development of acute component or new cSDH	Secondary
Requirement for cSDH surgery	Secondary
Death, stroke, myocardial infarction, or thromboembolic complications	Secondary
New-onset seizures	Secondary
Change in modified Rankin Scale / Markwalder Grading Scale scores	Secondary
Quality of life	Secondary
Healthcare resource use	Secondary
Occurrence of all adverse events through 6 months (primary safety endpoint)	Safety
Death, stroke, myocardial infarction, thromboembolic complications	Safety
New-onset seizures	Safety

Subgroup Analysis

Pre-specified cohorts: surgical vs nonsurgical management, with separate randomization within each cohort.

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.

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

Content summarized and formatted by NeuroTrials.ai.

MEMBRANE

(2025)

Objective

To evaluate the safety and effectiveness of TRUFILL n-butyl cyanoacrylate (n-BCA) for middle meningeal artery (MMA) embolization versus standard-of-care alone in patients with chronic subdural hematoma (cSDH).

Study Summary

• Study design protocol paper — results not yet available
• Trial enrollment completed February 2024; study completion expected 2025
• Will report primary endpoint of residual/re-accumulation of hematoma (>10 mm) at 6 months or reoperation within 6 months
• Background literature cited suggests MMA embolization may reduce recurrence rates to 2–3%, compared with 11% post-surgery and 17% with pharmacotherapy

Intervention

TRUFILL n-butyl cyanoacrylate (n-BCA) Liquid Embolic System delivered via catheter under fluoroscopic guidance to embolize the middle meningeal artery, in addition to standard-of-care (surgical or nonsurgical management).

Inclusion Criteria

Adults aged 18–90 years with cSDH causing mass effect and correlated clinical symptoms, mRS ≤3, demonstrated hematoma stability, and technically feasible TRUFILL n-BCA treatment. Nonsurgical cohort required midline shift <10 mm and hematoma thickness >10 mm.

Study Design

Arms: TRUFILL n-BCA MMA embolization + standard-of-care (surgical or nonsurgical) vs. Standard-of-care alone; randomized 1:1 within surgical and nonsurgical cohorts (~376 total participants)

Patients per Arm: ~376 total, randomized 1:1 within surgical and nonsurgical cohorts

Outcome

• Study design/protocol publication — no efficacy or safety results reported
• Primary effectiveness endpoint: residual or re-accumulation of hematoma >10 mm at 6 months, or reoperation/surgical procedure within 6 months
• Primary safety endpoint: occurrence of all adverse events through 6 months
• Results pending; trial expected to complete in 2025

Bottom Line

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.

Study Design

Study Type: Prospective, multicenter, open-label, randomized-controlled trial (study design/protocol publication)
Randomization: Yes
Blinding: Open-label (independent imaging core laboratory assesses primary effectiveness endpoint)
Sample Size: 376
Follow-up: 12 months (visits at 1, 3, 6, and 12 months post procedure)
Centers: 35
Countries: United States, China

Primary Outcome

Definition: 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. Primary safety: occurrence of all adverse events through 6 months.

Control	Intervention	HR/OR	P-value
		-

Limitations & 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.

Citation

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

View Original Publication →

MEMBRANE

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

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Subgroup Analysis

Criticisms

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