The MEMBRANE randomized controlled trial (RCT), presented at the 2024 Society of Vascular and Interventional Neurology (SVIN) annual meeting, provides new evidence supporting the use of middle meningeal artery (MMA) embolization as an adjunct to standard care for chronic subdural hematoma (cSDH) patients. The study, led by Ansaar Rai (West Virginia University Rockefeller Neuroscience Institute) and Christopher Kellner (Mount Sinai Health System), demonstrated a significant positive treatment effect in favor of Trufill n-BCA for MMA embolization over standard of care.
Study Design and Patient Population
The prospective, multicenter, open-label MEMBRANE RCT enrolled 376 cSDH patients across 28 US sites and two centers in China. Patients were randomized to either surgical treatment (n=265) or non-surgical medical management (n=111), with further randomization within these groups to receive MMA embolization plus standard care or standard care alone. The primary effectiveness endpoint was defined as residual cSDH or re-accumulation (>10mm) at six months, or reoperation or surgical cSDH treatment within six months post-randomization. The primary safety endpoint was the occurrence of any adverse events through six months. Secondary endpoints included functional outcomes at three months, mean change in hematoma volume, new seizure onset, and modified Rankin scale (mRS) distribution change.
The study population had an average age of approximately 70 years, with a predominance of male patients. Headache was the most common presenting symptom, and about 25% of patients were on antithrombotic medications. The mean hematoma thickness was close to 15mm in the surgical cohort and around 16mm in the non-surgical cohort, with a higher average midline shift in the surgical group.
Key Findings
The MEMBRANE trial met its primary effectiveness endpoint, demonstrating a significant and positive treatment effect in favor of MMA embolization versus standard of care, with a common odds ratio (OR) of 0.529 (90% confidence interval, 0.308–0.909). This indicates that the failure rate in the embolization group was almost half that of the non-embolization group. Subgroup analysis revealed favorable outcomes with MMA embolization in both the surgical management (OR, 0.475) and non-surgical medical management arms (OR, 0.615), with statistical significance reached in the surgical cohort.
Failure rates across the study arms were 8.5% with surgery plus embolization, 20.2% with surgery only, 20% with non-surgical medical management plus embolization, and 27% with non-surgical medical management only.
Safety and Functional Outcomes
Primary safety endpoint results showed a similar distribution of all adverse events between the embolization and non-embolization groups at six months. The rate of procedure-related serious adverse events was 3.3%, and the rate of device-related serious adverse events was 2.2% across 181 patients who received MMA embolization. The rate of all strokes (minor or major) was between 2–3% in both cohorts.
Regarding functional outcomes, 85.3% of patients who received embolization achieved good functional outcomes (mRS score of 0–2 or no worsening in patients with a baseline mRS of 3) at three months, compared to 77% in patients who received surgical or non-surgical management alone. MMA embolization was deemed statistically non-inferior to the standard of care and almost achieved superiority, with a risk difference of 0.073.
Impact and Context
According to Rai, the primary effectiveness endpoint subgroup analysis by age showed that the most significant treatment effect was in patients over the age of 75 in the surgical cohort. This suggests that adjunctive MMA embolization has the strongest treatment effect in this vulnerable population with large hematomas requiring surgical evacuation.
Additional secondary effectiveness endpoints revealed a higher rate of complete cSDH resolution with MMA embolization, lower rebleeding probability rates, and a much lower rate of surgical reoperation in the MMA embolization groups. All-cause mortality was also notably lower in the embolization arm (4%) versus the non-embolization arm (12.4%).
"The question that was asked—similarly to the other trials—was whether MMA embolisation has a role [to play] in the treatment of chronic subdural haematomas," Rai noted. He emphasized the increasing incidence and prevalence of subdural hematomas in the growing population over 65, highlighting its significance as one of the most common neurosurgical diagnoses leading to disability.
