EMPROTECT
(2025)Objective
To evaluate whether middle meningeal artery (MMA) embolization reduces the recurrence rate of chronic subdural hematoma (CSDH) at 6 months in patients undergoing surgery and at high risk of recurrence.
Study Summary
• Procedure-related complications were infrequent and mostly minor.
Intervention
Multicenter, open-label, randomized clinical trial with blinded endpoint assessment conducted at 12 neurosurgical centers in France. Patients who had surgery for a first or recurrent CSDH and were considered at high risk of recurrence were randomized 1:1 to receive MMA embolization within 7 days post-op (microparticles) or standard medical care alone.
Inclusion Criteria
Patients ≥18 years old who underwent surgery for CSDH and were at high risk for recurrence (e.g., recurrence history, anticoagulant use, large hematoma volume).
Study Design
Arms: MMA Embolization vs. Standard Medical Care
Patients per Arm: MMA Embolization: 171; Standard Care: 171
Outcome
• Adjusted absolute difference: −6% (95% CI, −14% to 2%)
• Repeat surgery: 4.3% (embolization) vs. 8.3% (standard); P=0.14
• Procedure-related complications: minor in 1.8%, major in 0.6%
• No significant differences in any secondary endpoints
Bottom Line
In patients who underwent surgery for CSDH recurrence or a first CSDH episode who are at high risk of recurrence, MMA embolization did not lead to a significantly lower rate of recurrence at 6 months compared with standard medical care alone.
Major Points
- Multicenter, open-label, randomized trial with blinded end point assessment across 12 French centers
- Primary outcome showed no significant difference in 6-month CSDH recurrence (14.8% vs 21.0%, OR 0.64, P = 0.13)
- No significant differences in any secondary outcomes including repeat surgery, mortality, or disability
- Low complication rate: 1 major (0.6%) and 3 minor (1.8%) embolization-related complications
- 26 of 171 patients (15.2%) randomized to embolization did not receive the intervention
- Effect estimate magnitude consistent with other recent trials using different embolic agents
Study Design
- Study Type
- Multicenter, open-label, randomized clinical trial with blinded end point assessment
- Randomization
- Yes
- Blinding
- Open-label with blinded assessment of primary end point by independent adjudication committee
- Sample Size
- 342
- Follow-up
- 6 months with final follow-up on November 2, 2023
- Centers
- 12
- Countries
- France
Primary Outcome
Definition: CSDH recurrence rate at 6 months, defined as reappearance of homolateral CSDH with midline shift ≥5 mm or symptomatic homolateral CSDH, homolateral CSDH >10 mm thickness, need for repeat surgery, or need for hospital admission related to homolateral CSDH recurrence
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 33/157 (21.0%) | 24/162 (14.8%) | - (0.36-1.14) | 0.13 |
Limitations & Criticisms
- Open-label design may introduce bias despite blinded endpoint assessment
- Study may have lacked statistical power - recurrence rate was higher and benefit smaller than expected
- Only microparticles (300-500 μm) were used; choice of embolic agent may have affected results
- Study population limited to surgical patients at high risk - results may not generalize to all CSDH patients
- Embolization performed within 7 days after surgery, whereas other trials used pre-operative timing
- 15.2% of patients randomized to embolization did not receive intervention
- Single country study in France limits external validity
Citation
JAMA. 2025;334(2):127-135. doi:10.1001/jama.2025.7583