Chronic Subdural HematomaPhase 1SAFER-MMAENCT07729098
Intra-Arterial Bevacizumab as an Adjunct to Middle Meningeal Artery Embolization for Chronic Subdural Hematoma
A Phase 1 study testing Bevacizumab (intra-arterial) in people with Chronic Subdural Hematoma, run by Dheeraj Gandhi.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Chronic Subdural Hematoma
- What is being tested?
- Bevacizumab (intra-arterial)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2027to 1 Jun 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: 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
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.
Read the detailed description
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.
- Conditions
- Chronic Subdural Hematoma
- Being tested
- Bevacizumab (intra-arterial)
- Keywords
- bevacizumab, middle meningeal artery embolization, intra-arterial chemotherapy, VEGF
- Medical subject headings
- Hematoma, Subdural, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bevacizumab (intra-arterial)Drug
Single intra-arterial infusion of bevacizumab (reference product or FDA-approved biosimilar) at 2.0, 3.5, or 5.0 mg/kg, delivered via microcatheter into the middle meningeal artery over 5-10 minutes, immediately before MMAE.
| Study group | Role | What they receive |
|---|---|---|
| IA-BEV + MMAE | Experimental | Participants receive intra-arterial bevacizumab (dose per assigned cohort: 2.0, 3.5, or 5.0 mg/kg) via selective MMA microcatheter infusion immediately prior to standard-of-care middle meningeal artery embolization, within the same procedural session. Receives: Drug: Bevacizumab (intra-arterial) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities
Incidence of dose-limiting toxicities probably or definitely related to IA-BEV
Measured: 30 Days of Treatment
Incidence of SAE's
Incidence of dose-limiting toxicities (DLTs) and serious adverse events (SAEs) probably or definitely related to IA-BEV
Measured: 30 Days of Study Treatment
Secondary outcomes (7)
Incidence of acute neurological worsening
Incidence of acute neurological worsening (≥2-point NIHSS increase, NIHSS motor sub-score increase, or GCS decline)
Measured: Within 24 hours post-procedure
Volumetric change in cSDH size
Volumetric change in cSDH size on serial neuroimaging
Measured: 30, 90, and 180 days
Rates of surgical rescue, unplanned hospitalization, neurological death, and all-cause mortality
Measured: Through 6 months
Functional status
As assessed using modified Rankin Scale (mRS)
Measured: 30, 90, and 180 days
Neurological Status
Neurological deficit is assessed using the National Institutes of Health Stroke Scale (NIHSS), a scale ranging from 0 to 42, with higher scores indicating more severe neurological impairment (worse outcome)
Measured: 30 and 180 days
Adverse events attributable to the MMAE procedure itself
Measured: through study completion, an average of 1 year
Health-Related Quality of Life
As measured by the 36-Item Short Form Health Survey (SF-36)
Measured: 30, 90, 180 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2026
- Study start1 Jan 2027 (estimated)
- Primary completion1 Jan 2029 (estimated)
- Study completion1 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Subdural HematomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Sequential 3+3 dose-escalation cohorts (not separate arms)
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dheeraj Gandhi
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dheeraj Gandhi, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07729098
- Sponsor's protocol ID
- SM-UMB
- Other IDs
- SM-UMB
- Acronym
- SAFER-MMAE
- Status last verified
- Jul 2026
- First submitted
- 16 Jul 2026
- Last updated
- 27 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07729098
- Acronym / sponsor ID
- SAFER-MMAE / SM-UMB
- Conditions
- Chronic Subdural Hematoma
- Keywords
- bevacizumab, middle meningeal artery embolization, intra-arterial chemotherapy, VEGF
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Dheeraj GandhiUniversity, hospital or other
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 1 Jan 2029 (estimated)
- Study completion
- 1 Jun 2029 (estimated)
- First posted
- 27 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Sequential 3+3 dose-escalation cohorts (not separate arms)
| Arm | Type | Receives |
|---|---|---|
| IA-BEV + MMAE | Experimental | Drug: Bevacizumab (intra-arterial)Participants receive intra-arterial bevacizumab (dose per assigned cohort: 2.0, 3.5, or 5.0 mg/kg) via selective MMA microcatheter infusion immediately prior to standard-of-care middle meningeal artery embolization, within the same procedural session. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bevacizumab (intra-arterial)Single intra-arterial infusion of bevacizumab (reference product or FDA-approved biosimilar) at 2.0, 3.5, or 5.0 mg/kg, delivered via microcatheter into the middle meningeal artery over 5-10 minutes, immediately before MMAE. | Drug | IA-BEV + MMAE |
Primary outcome
Incidence of dose-limiting toxicities
Time frame: 30 Days of Treatment
Incidence of dose-limiting toxicities probably or definitely related to IA-BEV
Incidence of SAE's
Time frame: 30 Days of Study Treatment
Incidence of dose-limiting toxicities (DLTs) and serious adverse events (SAEs) probably or definitely related to IA-BEV
7 secondary outcomes
Incidence of acute neurological worsening
Time frame: Within 24 hours post-procedure
Volumetric change in cSDH size
Time frame: 30, 90, and 180 days
Rates of surgical rescue, unplanned hospitalization, neurological death, and all-cause mortality
Time frame: Through 6 months
Functional status
Time frame: 30, 90, and 180 days
Neurological Status
Time frame: 30 and 180 days
Adverse events attributable to the MMAE procedure itself
Time frame: through study completion, an average of 1 year
Health-Related Quality of Life
Time frame: 30, 90, 180 Days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2026.
- Individual participant dataSharing planned: No
Related trials for Chronic Subdural Hematoma
RecruitingObservational study
Effect of Different Intravenous Fluids on Post-operative Chronic Subdural Hematoma Size and Recurrence
Chronic Subdural Hematoma
Recruiting
Middle Meningeal Artery Embolisation in Chronic Subdural Hematoma
Chronic Subdural Hematoma
Not yet recruitingPhase 4
Propofol Target-Controlled Infusion Versus Dexmedetomidine for Sedation During Chronic Subdural Hematoma Surgery Under Local Anesthesia
Chronic Subdural Hematoma
RecruitingObservational study
Study On Histoacryl Used For Embolization Of Middle Meningeal Artery (MMA) In Chronic Subdural Hematoma (CSDH)
Subdural Hematoma, Subdural Hematoma, Chronic
Recruiting
MMA Embolization With NeoCast for Subacute and Chronic Subdural Hematoma
Subdural Hematoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bevacizumab (intra-arterial) in people with Chronic Subdural Hematoma, run by Dheeraj Gandhi.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kaitlyn Henry, MS (410-328-0939, khenry@som.umaryland.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicities (time frame: 30 Days of Treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2026.