ENRICH
Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage
Clinical Question
Does early minimally invasive surgical removal of hematoma plus guideline-based medical management result in better functional outcomes at 180 days compared to guideline-based medical management alone in patients with acute supratentorial intracerebral hemorrhage?
Study Overview
Objective
To evaluate the effectiveness of minimally invasive parafascicular surgery (MIPS) in treating spontaneous intracerebral hemorrhage (ICH).
Study Summary
Rapid surgical minimally invasive evacuation of lobar ICH improved outcomes, reduced ICU and hospital stay, and decreased the need for decompressive hemicraniectomy compared to conservative treatment..
Intervention
Minimally invasive parafascicular surgery (MIPS) within 24 hours from last known well versus conservative treatment.
Patients per Arm
150 patients per arm
Bottom Line
Minimally invasive hematoma evacuation performed within 24 hours of onset improved functional outcomes at 180 days for patients with acute intracerebral hemorrhage, particularly those with lobar hemorrhages, compared to medical management alone. This approach also resulted in lower 30-day mortality and a reduced need for decompressive craniectomy, with a low rate of postoperative rebleeding.
Major Points
- 300 patients were enrolled (150 to surgery, 150 to control), of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages.
- After 175 patients were enrolled, an adaptation rule was triggered to enroll only patients with lobar hemorrhages due to futility criterion met for anterior basal ganglia location.
- The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981).
- The effect of surgery appeared to be attributable to intervention for lobar hemorrhages (mean difference, 0.127; 95% Bayesian credible interval, 0.035 to 0.219), with no significant benefit for anterior basal ganglia hemorrhages (mean difference, -0.013; 95% Bayesian credible interval, -0.147 to 0.116).
- The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group.
- Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration.
- Decompressive hemicraniectomy was performed in 5 patients (3.3%) in the surgery group and in 30 patients (20%) in the control group.
Design
Study Type: Prospective, multicenter, adaptive, randomized trial with end-point adjudication
Randomization: 1
Blinding: Outcome adjudication was masked by a central independent neuropsychologist reviewing audio-recorded structured interviews with redacted identifying information and group assignment.
Enrollment Period: December 1, 2016, to August 24, 2022
Follow-up Duration: 180 days
Centers: 37
Countries: United States
Sample Size: 300
Analysis: Bayesian primary analysis with pooling of data from two hemorrhage locations. Prespecified threshold for superiority: posterior probability of at least 0.975. Bayesian multiple imputation for missing 180-day mRS scores. Complementary Bayesian hierarchical model for subgroup analysis. Analyses performed with FACTS (Fixed and Adaptive Clinical Trial Simulator), version 6.5, and R software, version 4.3.
Inclusion Criteria
- Persons 18 to 80 years of age
- CT-confirmed supratentorial, spontaneous, acute intracerebral hemorrhage — lobar or anterior basal ganglia location
- Hematoma volume of 30 to 80 ml
- Glasgow Coma Scale score between 5 and 14
- NIH Stroke Scale score >5
- Prehemorrhage mRS score 0 to 1
- Surgery could be initiated within 24 hours of time last known well
Exclusion Criteria
- Uncorrectable coagulopathy
- Need for long-term anticoagulation
- Very poor or very good neurologic exam
- Intraventricular hemorrhage >50% of either lateral ventricle
- Primary thalamic or infratentorial hemorrhage
- Secondary cause of ICH
Arms
| Field | Surgery Group | Control |
|---|---|---|
| Intervention | Minimally invasive trans-sulcal parafascicular surgery using BrainPath and Myriad device, plus guideline-based medical management | Guideline-based medical management alone |
| Duration | Single surgery with 180-day follow-up | 180-day follow-up |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Utility-weighted modified Rankin Scale score at 180 days | Primary | 0.374 | 0.458 | Posterior probability of superiority 0.981 | |
| Postoperative rebleeding with neurologic deterioration | Secondary | NA | 5 (3.3%) | ||
| ICU length of stay (mean days ± SD) | Secondary | 9.7 ± 7.6 | 6.9 ± 6.8 | Difference -2.832 (95% BCI -4.527 to -1.134) | |
| Hospital length of stay (mean days ± SD) | Secondary | 18.1 ± 11.9 | 14.9 ± 11.2 | Difference -3.125 (95% BCI -5.903 to -0.393) | |
| Surgery effect on ordinal modified Rankin scale — at discharge or 7 days | Secondary | OR 0.376 (95% BCI 0.230 to 0.577) | |||
| Surgery effect on ordinal modified Rankin scale — at 30 days | Secondary | OR 0.504 (95% BCI 0.326 to 0.741) | |||
| Surgery effect on ordinal modified Rankin scale — at 90 days | Secondary | OR 0.665 (95% BCI 0.437 to 0.970) | |||
| Surgery effect on ordinal modified Rankin scale — at 180 days | Secondary | OR 0.658 (95% BCI 0.433 to 0.957) | |||
| Hematoma reduction after completion of surgery (mean % ± SD) | Secondary | NA | 73.2 ± 37.8 | OR 0.871 (95% BCI 0.792 to 0.951) | |
| Hematoma volume after completion of surgery (mean ml ± SD) | Secondary | NA | 14.9 ± 21.7 | OR 0.725 (95% BCI 0.604 to 0.845) | |
| Score ≤3 on modified Rankin scale at 180 days | Secondary | 57 (41.0%) | 74 (50.3%) | Difference 9.2 (95% BCI -2.0 to 20.3) | |
| Death within 30 days (primary safety endpoint) | Adverse | 27 (18.0%) | 14 (9.3%) | Difference -8.7 (95% BCI -16.4 to -1.0) | Posterior probability 0.987 |
| Change in hematoma volume from baseline (ml, mean ± SD; primary safety endpoint) | Adverse | 4.0 ± 17.82 | -43.9 ± 30.09 | Difference -47.91 (95% BCI -53.59 to -42.36) | Posterior probability >0.999 |
| Postoperative rebleeding and neurologic deterioration | Adverse | NA | 5 (3.3%) | ||
| One or more serious adverse events | Adverse | 118 (78.7%) | 95 (63.3%) | Difference -15.3 (95% BCI -25.4 to -5.2) | Posterior probability 0.998 |
| Death in the hospital after randomization | Adverse | 19 (12.7%) | 7 (4.7%) | Difference -8.0 (95% BCI -14.5 to -1.8) | Posterior probability 0.994 |
Criticisms
- Adaptive design halted anterior basal ganglia enrollment early, reducing generalizability
- Not powered for subgroup comparisons
- No blinding of site personnel
- Imaging adjudication unblinded due to device artifacts
- No assessment of outcomes beyond 180 days
Subgroup Analysis
Surgical benefit was significant in lobar hemorrhages (mean difference 0.127; 95% BCI 0.035 to 0.219), but not in anterior basal ganglia (mean difference -0.013; 95% BCI -0.147 to 0.116). Trial adapted mid-course to exclude basal ganglia cases.
Funding
Nico
Based on: ENRICH (The New England Journal of Medicine, 2024)
Authors: G. Pradilla, J.J. Ratcliff, A.J. Hall, ..., and D.L. Barrow
Citation: N Engl J Med 2024;390:1277-89.
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