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ENRICH

Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage

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Year of Publication: 2024

Authors: G. Pradilla, J.J. Ratcliff, A.J. Hall, ..., and D.L. Barrow

Journal: The New England Journal of Medicine

Citation: N Engl J Med 2024;390:1277-89.

Link: https://www.nejm.org/doi/10.1056/NEJMoa2308440

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?

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 with 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
Utility-weighted modified Rankin Scale score at 180 days	Primary	0.374	0.458
Death within 30 days	Secondary	18.0%	9.3%
Postoperative rebleeding with neurologic deterioration	Secondary		3.3%
ICU length of stay (median)	Secondary	5.0 (IQR 3.0–8.0)	3.0 (IQR 2.0–6.0)
Hospital length of stay (median)	Secondary	10.0 (IQR 7.0–16.0)	7.0 (IQR 5.0–11.0)
Mechanical ventilation (median days)	Secondary	1.0 (IQR 0.0–4.0)	0.0 (IQR 0.0–1.0)
Decompressive hemicraniectomy	Secondary	20%	3.3%
Survival at 180 days	Secondary	77%	80%

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), but not in anterior basal ganglia (mean difference -0.013). 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.

Content summarized and formatted by NeuroTrials.ai.

ENRICH

(2024)

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.

Inclusion Criteria

Spontaneous ICH, age 18-80 years, lobar or anterior basal ganglia location, size 30-80 ml, GCS 5-14, NIHSS > 5, mRS 0-1, surgery within 24h from LKW, IVH > 50% of either lateral ventricle.

Study Design

Arms: Minimally Invasive Parafascicular Surgery (MIPS) vs. Conservative Treatment

Patients per Arm: 150 patients per arm

Outcome

• Uw-mRS at 180 days (mean): MIPS 0.47, Conservative 0.37 (Difference 0.084, CI 0.005 to 0.163). • Anterior BG Uw-mRS: MIPS 0.34, Conservative 0.38 (Difference -0.013, CI -0.147 to 0.116). • Lobar Uw-mRS: MIPS 0.51, Conservative 0.37 (Difference 0.127, CI 0.035 to 0.219). • ICU Stay (days): MIPS 6.9, Conservative 9.7 (Difference -2.832, CI -4.527 to -1.134). • Hospital Stay (days): MIPS 14.9, Conservative 18.1 (Difference -3.125, CI -5.903 to -0.393). • Hematoma size reduction: 73%, 15 ml. • mRS 0-3 at 180 days: MIPS 50%, Conservative 41% (Difference 9.2%, CI -2.0 to 20.3). • Decompressive Hemicraniectomy: MIPS 3.3%, Conservative 20% (Difference -16.6%, CI -23.9 to -9.9)..

Bottom Line

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.

Study Design

Study Type: Prospective, multicenter, adaptive, randomized trial with end-point adjudication
Randomization: Yes
Blinding: Outcome adjudication was masked by a central independent neuropsychologist reviewing audio-recorded structured interviews with redacted identifying information and group assignment.
Sample Size: 300
Follow-up: 180 days
Centers: 37
Countries: United States

Primary Outcome

Definition: Utility-weighted modified Rankin Scale score at 180 days

Control	Intervention	HR/OR	P-value
0.374	0.458	- (0.005 to 0.163 (difference))	-

Limitations & 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

Citation

N Engl J Med 2024;390:1277-89.

View Original Publication →

ENRICH

Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Criticisms

Subgroup Analysis

Funding

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