Intra-Arterial Bevacizumab as an Adjunct to Middle Meningeal Artery Embolization for Chronic Subdural Hematoma

Chronic subdural hematoma (cSDH) is a common and growing neurological condition, particularly in older adults, and standard surgical treatment carries meaningful perioperative risk. Middle meningeal artery embolization (MMAE) has emerged as an effective standalone or adjunctive treatment, but a meaningful proportion of patients do not achieve adequate hematoma resolution with embolization alone. Vascular endothelial growth factor (VEGF)-driven angiogenesis within the hematoma membrane is believed to underlie continued hematoma growth and treatment failure. Bevacizumab, an anti-VEGF monoclonal antibody, may interrupt this process when delivered directly into the middle meningeal artery at the time of embolization. This study will enroll up to 18 adults undergoing MMAE as standard of care, assigning them to one of three sequential dose cohorts (2.0, 3.5, or 5.0 mg/kg) of intra-arterial bevacizumab using a 3+3 dose-escalation design. The primary objective is to characterize the safety and tolerability of IA-BEV and identify a maximum tolerated dose. Secondary objectives include volumetric hematoma response, functional and neurological outcomes, and clinical event rates through 180 days. Exploratory objectives include correlating treatment response with Nakaguchi radiographic subtype, dual-energy CT membrane imaging biomarkers, and VEGF concentrations sampled from the middle meningeal artery at the time of the procedure.

Inclusion criteria

• Age 18-85 years
• Scheduled to undergo MMAE as standard of care for cSDH, no concurrent surgical evacuation planned (prior surgery for the target cSDH allowed if ≥14 days elapsed)
• Radiographically confirmed cSDH meeting specified unilateral/bilateral density criteria
• cSDH volume 20-100 cc
• Midline shift <8 mm
• Markwalder Grade 1 or 2
• Subject or LAR able to provide written informed consent

Exclusion criteria

• Requires immediate/urgent surgical evacuation
• Prior large craniotomy, membranectomy, or MMAE for the current target cSDH
• Life expectancy <1 year
• Uncontrolled bleeding disorder (INR >1.7, aPTT >35s, platelets <100,000/μL)
• Concurrent intracranial hemorrhage outside the target subdural space
• Persistent neurological deficit from another acute/chronic neurological condition
• Pregnancy or lactation
• Known/suspected intracranial neoplasm or mass lesion
• Active alcohol/substance use disorder within 12 months
• Baseline mRS ≥3
• Uncontrolled severe hypertension (SBP >220 or DBP >120, or IV antihypertensive need within 24h pre-procedure)
• Thromboembolic event within 6 months (DVT, PE, TIA, stroke)
• Contraindication to VTE prophylaxis
• eGFR <60 mL/min/1.73m² or acute kidney injury at screening
• Known hypersensitivity to bevacizumab or its components