n-Butyl Cyanoacrylate Embolization for Chronic Subdural Hematoma

Key Takeaways

• Adjunct embolization was associated with a lower rate of the prespecified 6-month composite effectiveness end point than standard care alone.
• Good functional outcome at 3 months met the trial’s noninferiority criteria.
• Overall adverse-event and serious-adverse-event burdens were broadly similar between groups, with one adjudicated device-related event reported.

Adjunct middle meningeal artery embolization with the TRUFILL n-butyl cyanoacrylate system was linked to fewer 6-month composite treatment-failure events than standard care alone in symptomatic chronic subdural hematoma. In the MEMBRANE randomized clinical trial, events occurred in 17 of 146 participants versus 29 of 131 participants. The common odds ratio was 0.53, with a 90% CI of 0.31 to 0.91 and P=.04. MEMBRANE was a prospective, multicenter, open-label randomized clinical trial with outcomes tracked through 6 months, including functional and safety findings.

Investigators conducted the trial at 30 hospitals in the United States and China from May 27, 2021, to February 6, 2024. Eligible participants were 18 to 90 years old, had symptomatic chronic subdural hematoma, and had prerandomization modified Rankin Scale scores of 3 or less. Site physicians first selected surgical or nonsurgical management; participants in the surgical cohort underwent decompression before randomization, and participants in both cohorts were then randomized 1:1 to embolization plus standard care or standard care alone. Among 390 enrolled participants, 376 were randomized, 371 formed the as-treated set, and 312 formed the per-protocol set across parallel surgical and nonsurgical cohorts.

The primary effectiveness end point was residual or re-accumulated hematoma greater than 10 mm at 6 months or requiring a surgical procedure on the chronic subdural hematoma within 6 months. An independent core laboratory assessed the imaging component of the end point. Complete hematoma resolution at 6 months was 73.0% with embolization plus standard care and 64.6% with standard care alone, while rebleeding was 10.2% versus 16.1%. The proportion requiring surgery was 3.8% versus 10.0% at both 3 and 6 months, and good functional outcome at 3 months met noninferiority criteria with a risk difference of 0.07 and a 90% CI of -0.001 to 0.15. Overall, embolization was associated with less radiographic or surgical treatment failure over 6 months.

The primary safety end point was incidence of adverse events through 6 months. A total of 414 adverse events occurred in 130 of 181 participants receiving embolization, compared with 392 events in 124 of 190 receiving standard care alone. Serious adverse events occurred in 51 of 181 versus 60 of 190, and the one device-related event was a transient facial nerve palsy that resolved the same day. Two strokes were judged unrelated to the device and possibly related to embolization, and the rate of death, stroke, myocardial infarction, or thromboembolic complications was numerically lower with embolization. Overall safety burden was broadly similar across groups over 6 months.

The study device was the TRUFILL n-butyl cyanoacrylate liquid embolic system, composed of n-BCA, ethiodized oil, and tantalum powder. Mean procedural time was 71.2 minutes, conscious sedation was used in 31 of 180 procedures, and treating physicians reported successful embolization in 178 of 180 procedures. Follow-up visits occurred at 1, 3, 6, and 12 months, each with required CT imaging, and the 6-month visit was required in clinic. Antithrombotic medications were permitted, crossover to embolization was not, and nonsurgical management could include anticoagulation changes, statins, observation, repeat imaging, and lifestyle modification. Twelve-month outcomes remain pending, and the authors cited open-label conduct, prerandomization surgical assignment, and the COVID-19 pandemic as limitations.