Safety And Efficacy of Intra-aRterial BEV (IA-BEV) as an Adjunctive Treatment During Middle Meningeal Artery Embolization (MMAE) in Non-Surgical Chronic Subdural Hematoma (cSDH) Patients
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 18
- 主要终点
- Incidence of dose-limiting toxicities
研究概览
简要总结
This is a Phase 1, open-label, single-center, dose-escalation study evaluating the safety and tolerability of intra-arterial bevacizumab (IA-BEV) given as an adjunct to middle meningeal artery embolization (MMAE) in adults with non-surgical chronic subdural hematoma (cSDH). Up to 18 participants who are already scheduled to undergo MMAE as standard of care will receive a single dose of bevacizumab, delivered directly into the middle meningeal artery immediately before embolization, during the same procedure. Three dose levels (2.0, 3.5, and 5.0 mg/kg) will be tested using a standard 3+3 dose-escalation design to identify the maximum tolerated dose. The study will also collect imaging and blood biomarker data to help understand which patients may benefit most from this combined treatment approach.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Incidence of dose-limiting toxicities
时间窗: 30 Days of Treatment
Incidence of dose-limiting toxicities probably or definitely related to IA-BEV
Incidence of SAE's
时间窗: 30 Days of Study Treatment
Incidence of dose-limiting toxicities (DLTs) and serious adverse events (SAEs) probably or definitely related to IA-BEV
次要结局
- Adverse events attributable to the MMAE procedure itself(through study completion, an average of 1 year)
- Incidence of acute neurological worsening(Within 24 hours post-procedure)
- Volumetric change in cSDH size(30, 90, and 180 days)
- Rates of surgical rescue, unplanned hospitalization, neurological death, and all-cause mortality(Through 6 months)
- Functional status(30, 90, and 180 days)
- Neurological Status(30 and 180 days)
- Health-Related Quality of Life(30, 90, 180 Days)
研究者
Dheeraj Gandhi
MBBS, MD, FACR
University of Maryland, Baltimore