Safety of Intra-Arterial Bevacizumab in Chronic Subdural Hematoma: Phase 1 Analysis

Introduction/Purpose Chronic subdural hematoma (CSDH) is often treated with medical management or surgical evacuation; more recently, middle meningeal artery embolization with occlusive materials has been explored as a promising endovascular approach to CSDH treatment. Vascular endothelial growth factor is a key part of the pro‐inflammatory cascade driving CSDH, and thus, is a potential therapeutic target. The objective of our pilot clinical trial is to characterize the safety of bevacizumab, an anti‐vascular endothelial growth factor receptor antagonist, for CSDH treatment. Materials and Methods A non‐randomized, open‐label parallel arm phase 1 clinical trial is currently in progress with targeted enrollment of 10 patients. Patients with unilateral or bilateral CSDHs with mixed density collections or evidence of subdural membranes were eligible. Patients with significant neurological deficits from CSDH necessitating emergent evacuation were ineligible. Patients received 2mg/kg bevacizumab per hemisphere infused intra‐arterially in the middle meningeal artery unilaterally (for unilateral CSDH, to side ipsilateral to CSDH) or bilaterally (for bilateral CSDH). Patients were observed for 6 months following treatment. An interim descriptive analysis of incidence of adverse events related to the treatment was conducted on patients enrolled to date. Results Of the 9 patients enrolled thus far, 55.6% (5/9) have completed long‐term follow‐up. During the study duration thus far, a total of 9 adverse events were abstracted; 8/9 (88.9%) were not related to the study treatment. One patient had an in‐hospital cerebrovascular event without post‐event clinical sequelae following procedure and treatment, which was thought to be potentially related to dislodgement of plaque during endovascular navigation rather than the bevacizumab itself. There were no incidence of neurological deterioration or mortality amongst enrolled patients. Conclusion This interim safety analysis suggests that intra‐arterial bevacizumab likely has favorable safety and tolerability. Bevacizumab is potentially a safe endovascular, targeted treatment for unilateral and bilateral CSDH in patients without severe neurological symptoms. Completion of the phase 1 trial is necessary to fully characterize the safety of this treatment.