Christopher P. Kellner, Ansaar Rai, Hazem Shoirah, Visish M. Srinivasan, Rishi Gupta, Robert M. Starke, Fawaz Al-Mufti, Charles C. Matouk, Benjamin Yim, Matthew R. Fusco, Jieqing Wan, Elizabeth Liptrap, Parita Bhuva, Ramesh Grandhi, Russell Cerejo, Jesse J. Liu, JJ Cherian, Q Y Zhang, Ian Kaminsky, Charles J. Prestigiacomo, E Orru’, Eugene Lin, Jay Howington, Avery Evans, T Mehta, SoHyun Boo, Ira Finch, T M Liu, R Chitale, Shahram Majidi, Brian T. Jankowitz, MEMBRANE Study Group, R Budzik, Michael Stiefel, Richard Williamson, Dimitri Sigounas, Frank Hellinger, E HAUCK, Bharathidasan Jagadeesan, Ricardo Hanel, Alexander Coon, Lucas Elijovich, Ryan Turner, Phong Vu, M Czaplicki, Reade De Leacy, J Fifi, Tomoyoshi Shigematsu, M. Travis Caton, Benjamin Rapoport, Gregory Lock, Thomas Oxley, Pouria Moshayedi, Krisztina Moldovan, Natalie Hall, Anne Yanda, Sarah Baggette, Osama Zaidat, Wayne Clark, Parker Miller, Gary Nesbit, ryan priest, Rachel Laursen, Sonesh Amin, Scott Rewinkel, David Lockwood, Jacob Bagley, Hormozd Bozorgchami, Aclan Dog⫧an, C C Kam, M Horikawa, Daniel Munger, Chirag Gandhi, Gurmeen Kaur, J Santarelli, Steven Shapiro, Haris Kamal, peter Pema, N Vora, A Alhajeri, Albert Yoo, Paul Hansen, Osman Mir, Jazba Soomro, Bizhan Aarabi, Jindal Gd, Timothy Miller, Neil Patel, Jonathan Pace, Passer Ja, Zoher Ghogawala, Wakhloo Ak, Jesse Jones, M R Harrigan, Jesse Schuette, Bryan Pukenas, J K Burkhardt, William Humphries, Ahmad Khaldi, Ryan Hebert
Importance: Middle meningeal artery embolization (MMAE) is a minimally invasive adjunctive treatment for chronic subdural hematoma (cSDH). The TRUFILL n-butyl cyanoacrylate (n-BCA) liquid embolic system is indicated for embolization of cerebral arteriovenous malformations for presurgical devascularization and may be appropriate for MMAE in patients with cSDH. Objective: To evaluate safety and effectiveness of the study device for MMAE plus standard of care vs standard of care alone in patients with cSDH. Design, Setting, and Participants: The Middle Meningeal Artery Embolization for the Treatment of Subdural Hematomas With TRUFILL n-BCA (MEMBRANE) trial was a prospective, multicenter, open-label, randomized clinical trial conducted from May 27, 2021, to February 6, 2024, at 30 hospitals (28 in the United States and 2 in China). Participants aged 18 to 90 years with symptomatic cSDH and a modified Rankin Scale score of 3 or less were enrolled. Interventions: Site physicians determined whether each patient required surgical or nonsurgical management. Participants in the surgical and nonsurgical cohorts were then randomized 1:1 to receive MMAE plus standard of care or standard of care alone. Main Outcomes and Measures: The primary effectiveness end point was residual or re-accumulation of hematoma (>10 mm; assessed by an independent core laboratory) at 6 months or requiring a surgical procedure on the cSDH within 6 months (conducted as an intention-to-treat analysis). The primary safety end point was incidence of adverse events through 6 months (conducted as an as-treated analysis). Results: A total of 376 participants (188 in MMAE plus standard of care and 188 in standard of care alone) were included. In the MMAE plus standard of care and standard of care alone groups, the mean (SD) age was 70.9 (10.6) and 70.3 (12.1) years, and 45 (23.9%) and 49 (26.1%) were female, respectively. Primary effectiveness end point events occurred in 17 of 146 participants receiving MMAE plus standard of care (11.6%) and 29 of 131 receiving standard of care alone (22.1%) (final estimate of common odds ratio: 0.53 [90% CI, 0.31-0.91]; P = .04), indicating statistically significant benefit for MMAE plus standard of care vs standard of care alone. Adverse events occurred in 130 of 181 participants in the MMAE plus standard of care group (71.8%) and 124 of 190 in the standard of care alone group (65.3%) through 6 months. MMAE plus standard of care treatment was noninferior to standard of care alone based on analysis of good functional outcome at 3 months, as assessed by the modified Rankin Scale. Conclusions and Relevance: In this randomized clinical trial, MMAE plus standard of care significantly reduced rates of recurrence and reoperation vs standard of care alone, without a significant increase in adverse events. Trial registration: ClinicalTrials.gov Identifier, NCT04816591.