Chronic Subdural Hematoma Treatment With Intra-Arterial Bevacizumab Injection (CHAI)

Chronic Subdural Hematoma Treatment With Avastin® (Bevacizumab) Intra-Arterial Injection: A Non-Randomized, Open-Label Phase 1/2 Clinical Trial

The goal of this clinical trial is to test whether infusing bevacizumab into the middle meningeal arteries can be used to treat chronic subdural hematomas (cSDH).

The main questions it aims to answer are:

• Is bevacizumab infusion safe in cSDH patients?
• Is bevacizumab infusion effective in treating cSDH?

Study Overview

• Status: Recruiting
• Conditions: Chronic Subdural Hematoma
• Intervention / Treatment: Drug: Bevacizumab 2 mg/kg; Drug: Bevacizumab 4 mg/kg

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Thuy Cao; Phone Number: 2362 856-342-2689; Email: cao-thuy@cooperhealth.edu

Study Locations

• United States
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Recruiting
      • Cooper University Health Care
      • Principal Investigator: Jane Khalife, MD
      • Contact: Cooper Neurological Institute; Phone Number: 855-306-3876; Email: cniresearch@cooperhealth.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients (≥18 years)

• Radiographic evidence of chronic subdural hematoma, including

  1. Persistence of subdural blood more than 10 days after index traumatic injury or event
  2. Presence of mixed density blood
  3. Presence of subdural membranes
• Can obtain informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization.

Exclusion Criteria:

• Pregnant, breastfeeding, or unwilling to practice contraception during participation in the study.
• Patients with concomitant intracranial pathology other than subdural hematoma (e.g., intracranial malignancy).
• Patients with known hypersensitivity to bevacizumab.
• Patients with radiographic evidence of mass effect.
• Patients have focal neurological deficits attributed to subdural hematoma.
• Patient had craniotomy or burr hole operative procedures performed in preceding two weeks prior to onset of subdural hematoma.
• Secondary causes apart from trauma for the chronic subdural hematoma, such as underlying vascular abnormality or tumor.
• Emergent surgical evacuation is required for the patient.
• Non-convexity chronic subdural hematoma, as the middle meningeal artery will not supply this area.
• Coagulation abnormalities, including platelet count <100,000 and/or international normalized ratio of <1.5 despite attempts for correction.
• Patients with known contraindications for angiography. Patients with contrast allergy will be premedicated with diphenhydramine and steroids.
• Patient has known active systemic infection or sepsis.
• Patient has contradiction to anesthetic agents used for conscious sedation/monitored anesthesia care (MAC).
• Patient has life expectancy of less than six months due to comorbid terminal conditions.
• Patient has a premorbid modified Rankin score (mRS) of 5 or greater.
• Concurrent participation in another research protocol for investigation of an experimental therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Unilateral cSDH/ 2mg/kg Arm; During phase 1, single 2mg/kg dose of bevacizumab to treat unilateral cSDH	Drug: Bevacizumab 2 mg/kg; Single 2mg/kg dose of bevacizumab to treat unilateral cSDH
Experimental: Phase 1 Bilateral cSDH/ 4mg/kg Arm; During phase 1, two 2mg/kg doses (cumulatively 4mg/kg) of bevacizumab to treat bilateral cSDH	Drug: Bevacizumab 4 mg/kg; Two 2mg/kg doses (cumulatively 4mg/kg) of bevacizumab to treat bilateral cSDH
Experimental: Phase 2 Unilateral cSDH/ 2mg/kg Arm; During phase 2, single 2mg/kg dose of bevacizumab to treat unilateral cSDH	Drug: Bevacizumab 2 mg/kg; Single 2mg/kg dose of bevacizumab to treat unilateral cSDH
Experimental: Phase 2 Bilateral cSDH/ 4mg/kg Arm; During phase 2, two 2mg/kg doses (cumulatively 4mg/kg) of bevacizumab to treat bilateral cSDH	Drug: Bevacizumab 4 mg/kg; Two 2mg/kg doses (cumulatively 4mg/kg) of bevacizumab to treat bilateral cSDH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Serious Adverse Events	Reported serious adverse events classified using MedDRA and CTCAE, in addition to treatment-related events and all other adverse events	Up to 3 months after study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Hematoma Recurrence	Rate of hematoma recurrence or progression requiring intervention and/or readmission	3 months after study treatment and 6 months after study treatment
Rate of Complete Hematoma Resolution	Rate of complete hematoma resolution compared to baseline on imaging	3 months after study treatment and 6 months after study treatment
Rate of Partial Hematoma Resolution	Rate of at least 50% or greater reduction in hematoma size from baseline on imaging	3 months after study treatment and 6 months after study treatment
Change in Hematoma Size	Change in hematoma size measured in millimeters on imaging	3 months after study treatment and 6 months after study treatment
Change in Clinical Neurological Symptom Scale Scores: NIHSS	Change in National Institutes of Health Stroke Scale (NIHSS) scores, scores range from 0 to 42, with higher scores indicating more severe neurological deficit	3 months after study treatment and 6 months after study treatment
Change in Clinical Neurological Symptom Scale Scores: GCS	Change in Glasgow Coma Scale (GCS) scores, ranging from 3 to 15 with lower score indicating more impaired consciousness	3 months after study treatment and 6 months after study treatment
Change in Clinical Neurological Symptom Scale Scores: mRS	Change in modified Rankin Scale (mRS) scores, ranges from 0-6 with higher score indicating worse functional outcome	3 months after study treatment and 6 months after study treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Anatomical Variants	Middle meningeal arteries with dangerous anastomoses observed on imaging	During the treatment procedure

Collaborators and Investigators

• Sponsor: The Cooper Health System
• Collaborators: Society of Vascular and Interventional Neurology
• Investigators: Study Chair: Manisha Koneru, MD, The Cooper Health System; Principal Investigator: Jane Khalife, MD, The Cooper Health System; Study Chair: Ajith J Thomas, MD, The Cooper Health System

Publications and helpful links

General Publications

• Khalife J, Tonetti DA, Shaikh H, Jovin T, Patel P, Thomas A. Intraarterial bevacizumab administration through the middle meningeal artery for chronic subdural hematoma. Stroke: Vascular and Interventional Neurology. 2023 Jul;3(4). doi:10.1161/svin.122.000722
• Khalife J, Koneru M, Tonetti DA, Shaikh HA, Jovin TG, Patel PD, et al. Intra-arterial selective bevacizumab administration in the middle meningeal artery for chronic subdural hematoma: An early experience in 12 Hemispheres. Stroke: Vascular and Interventional Neurology. 2024 Sept;4(5). doi:10.1161/svin.124.001409

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: June 28, 2024
• First Submitted That Met QC Criteria: July 14, 2024
• First Posted (Actual): July 19, 2024

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 25, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Bevacizumab; Vascular endothelial growth factor; Chronic subdural hematoma; Middle meningeal artery embolization; Chronic intracranial subdural hematoma
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Chronic Disease; Disease Attributes; Hemorrhage; Craniocerebral Trauma; Trauma, Nervous System; Intracranial Hemorrhages; Intracranial Hemorrhage, Traumatic; Hematoma, Subdural; Hematoma, Subdural, Chronic; Hematoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: 23-154

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No