ENRICH Trial: Minimally Invasive Surgical Evacuation of Intracerebral Hemorrhage
In patients with lobar (or anterior basal ganglia) intracerebral hemorrhage of 30–80 mL within 24 hours, does minimally invasive parafascicular surgery improve utility-weighted mRS at 180 days compared with standard medical management?
Pradilla G, et al. (NEJM 2024) · doi:10.1056/NEJMoa2308440 · 300 patients
Population
Included
- Lobar OR anterior basal ganglia ICH on baseline CT
- Hematoma volume 30–80 mL
- Within 24 hours of last known well
- Age 18+, presenting after ictus
- Persons 18 to 80 years of age
- Computed tomographic (CT) evidence of a supratentorial, spontaneous, acute intracerebral hemorrhage
- A hematoma volume of 30 to 80 ml (estimated by the local investigator using volume = (length x width x height) / 2)
- A score on the Glasgow Coma Scale (GCS) between 5 and 14, indicating mild-to-severe neurologic deficits
- A score on the National Institutes of Health (NIH) stroke scale of more than 5, representing moderate-to-severe disability
- A score before the hemorrhage occurred of 0 to 1 on the modified Rankin scale, representing little or no disability
- Surgery could be initiated within 24 hours after the time that they were last known to be well
- Hemorrhage in a lobar or anterior basal ganglia location (lobar = a lesion superficially located in the main lobes of the brain, typically the parietal, temporal, or frontal lobes; anterior basal ganglia = the caudate, putamen, and pallidum to the capsula externa, excluding the thalamus)
Excluded
- Deep ICH (thalamic/putaminal. Anterior basal ganglia subgroup halted for futility)
- Posterior fossa or brainstem ICH
- Volume <30 mL or >80 mL
- Pre-stroke severe disability
- Surgery >24 hours from LKW
- An uncorrectable coagulopathy
- A need for long-term anticoagulation
- Very poor or very good results on neurologic examination (GCS below 5 or above 14, or NIH stroke scale of 5 or less)
- An intraventricular hemorrhage involving more than 50% of either lateral ventricle
- A primary thalamic or infratentorial hemorrhage
- Any secondary cause of intracerebral hemorrhage (hemorrhagic conversion, trauma, ruptured aneurysm, arteriovenous malformation, vascular anomaly, Moyamoya disease, venous sinus thrombosis, a mass or tumor, or recurrent ICH within 1 year)
- A do-not-resuscitate or comfort-measures-only order
- Hematoma volume below 30 ml or above 80 ml
- More than 24 hours from last known normal
- A score on the modified Rankin scale above 1 before the hemorrhage occurred
- After an adaptation rule was triggered at the second interim analysis, new enrollment of patients with an anterior basal ganglia hemorrhage was stopped for futility; subsequent enrollment was restricted to lobar hemorrhage
Source: Pradilla G et al., N Engl J Med 2024;390(14):1277–1289; NCT02880878· Retrieved 2026-06-09
Primary Outcome — Bayesian Superiority
Bayesian response-adaptive design: Primary is utility-weighted mRS at 180 days; superiority by posterior P(sup) = 0.981 (threshold 0.975). No frequentist p-value. The 30-day mortality result shown below is the primary SAFETY endpoint, not the primary EFFICACY endpoint. Anterior basal ganglia subgroup was halted for futility — benefit is in LOBAR ICH.
Negligible absolute difference
30-day mortality (primary safety)
Study Arms
- Agent
- Minimally invasive trans-sulcal parafascicular surgery (BrainPath minimal access port + Myriad device, NICO Corporation)
- Route
- Surgical (trans-sulcal parafascicular corridor under general anesthesia)
- Frequency
- Single procedure
- Duration
- Initiated within 24 hours after the time the patient was last known to be well
- Co-interventions
- Plus guideline-based medical management identical to the control group; lifesaving conventional craniotomy or decompressive hemicraniectomy permitted as needed
A small craniotomy and durotomy provided exposure to a sulcus oriented along the long axis of the white-matter tracts; the trajectory to the hematoma was planned with imaging guidance. The hematoma was accessed through the BrainPath access port (allowing a bimanual technique with visualization) and evacuated with suction and the Myriad device (both FDA-cleared). Surgeons completed a manufacturer-organized prerequisite training course before the trial began. The mean hematoma-volume reduction was 73.2% (mean residual 14.9 ml); a volume of 15 ml or less after surgery was achieved in 109 patients (72.7%). Postoperative rebleeding with neurologic deterioration occurred in 5 patients (3.3%).
- Agent
- Guideline-based medical management (no hematoma evacuation)
- Route
- Medical
- Frequency
- Continuous, per clinical standardization guideline
- Co-interventions
- Treatment followed a clinical standardization guideline based on AHA/ASA intracerebral-hemorrhage recommendations; lifesaving conventional craniotomy or decompressive hemicraniectomy permitted as needed, but crossover to elective surgical evacuation was prohibited
The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale at 180 days, analyzed with a Bayesian model (prespecified posterior-probability-of-superiority threshold of 0.975). Surgery met the primary end point: 0.458 versus 0.374, difference +0.084 (95% Bayesian credible interval 0.005 to 0.163, posterior probability of superiority 0.981). Benefit was concentrated in lobar hemorrhage (+0.127, 95% Bayesian CrI 0.035 to 0.219); the anterior basal ganglia subgroup showed no benefit (−0.013, 95% Bayesian CrI −0.147 to 0.116). Death within 30 days was 9.3% (surgery) versus 18.0% (control). Because the primary analysis is Bayesian, no frequentist p-value or NNT applies to the primary efficacy result.
Safety
30-day mortality
9.3%
18%
ARD -8.7 pp (95% Bayesian CrI -16.4 to -1.0, posterior P=0.987). Approximately halved early mortality. NNT ~12 is approximate, from primary SAFETY endpoint (not primary efficacy).
Trial Design
Type
- Multicenter Bayesian response-adaptive randomized trial
- 37 US hospitals (Dec 2016 – Aug 2022)
- MIPS. Trans-sulcal parafascicular approach
- BrainPath® + Myriad® (NICO Corporation. Industry-funded)
- Surgery within 24 hours of last known well
- Anterior basal ganglia subgroup halted for futility at interim 2
Timeline
Enrolled Dec 1, 2016 – Aug 24, 2022; published NEJM April 2024
N
300
Enrollment
300 patients at 37 US hospitals (59 trained neurosurgeons; BrainPath + Myriad, NICO Corporation). Bayesian adaptive RAR design. Enrolled Dec 2016 – Aug 2022. Published NEJM 2024;390(14):1277–1289.
ClinicalTrials.gov
NCT02880878Bedside Pearl
For LOBAR (or selected anterior basal ganglia) ICH 30–80 mL within 24 hours, minimally invasive parafascicular surgery (BrainPath + Myriad) reduces 30-day mortality (9.3% vs 18.0%) and improves 180-day UW-mRS (Bayesian posterior P>0.98). Anterior basal ganglia subgroup was halted for futility; benefit is in LOBAR ICH.
See also