By Patrice Wendling | April 10, 2024 | Read this story at Medscape
The ENRICH trial, showing improved functional outcomes with surgical clot evacuation plus medical management, has now been published in The New England Journal of Medicine.
The trial results were first presented at the American Association of Neurological Surgeons (AANS) 2023 Annual Meeting, as reported by Medscape Medical News at that time.
The current paper, published online on April 10, points out that current guidelines do not support the routine use of surgery with conventional craniotomy to improve outcomes after an intracerebral hemorrhage (ICH).
Meta-analyses have suggested a benefit with minimally invasive surgery (MIPS) techniques, but minimally invasive catheter-based evacuation plus alteplase in the MISTIE-III trial did improve functional outcomes at 1 year.
In preliminary studies, minimally invasive trans-sulcal parafascicular ICH evacuation with access through a port in a sulcus oriented along the long axis of the white-matter tracts has been shown to be safe and successful at removing a large amount of hematoma, the investigators noted.
The ENRICH trial directly compared guideline-directed medical management alone or with early trans-sulcal MIPS using the BrainPath minimal access port and Myrid aspiration device and suction in 300 patients with a supratentorial ICH. The two devices (NICO Corporation) are federally approved.
Patients were eligible if they had a hematoma volume of 30-80 mL, if they had a Glasgow Coma Scale score between 5 and 14, and if surgery could be performed within 24 hours of their last-known normal. Three fourths had lobar hemorrhages, and 30.7% had anterior basal ganglia hemorrhages. After the first 175 patients, an adaption rule was triggered, and only those with lobar hemorrhages were enrolled.
The mean utility-weighted modified Rankin score at 180 days, the primary efficacy endpoint, was 0.458 in the surgery group and 0.374 in the control group.
The between-group difference was 0.084 (Bayesian 95% CI, 0.005-0.163), reflecting a clinically meaningful effect as defined by a between-group difference of at least 0.075.
The mean between-group difference was 0.127 among those with lobar hemorrhages (95% CI, 0.035-0.219) and -0.013 among those with basal ganglia hemorrhages (95% CI, -0.147 to 0.116).
“We found a powerful effect for lobar hemorrhages,” study investigator Gustavo Pradilla, MD, Emory University School of Medicine, Atlanta, Georgia, told Medscape Medical News. “We don’t know if this is going to be beneficial for basal ganglia patients because we stopped enrolling them and the sample size only has about 100 patients who had basal ganglia. So, we cannot draw conclusions from that sample.”
New Secondary and Exploratory Analyses
The current paper provides new details on variety of outcomes, Pradilla noted, including the primary safety endpoint of 30-day mortality, which was nearly halved from 18% with medical treatment alone to 9.3% in the surgery group (between-group difference, -8.7; Bayesian 95% CI, -16.4 to -1.0).
At the final 180-day follow-up, 30 patients (20%) in the surgery group and 35 patients (23%) in the control group had died from any cause.
In the surgery group, one or more serious adverse events occurred in 95 patients (63.3%), and five patients had rebleeding associated with neurologic deterioration after surgery. In the control group, 118 patients (78.7%) had one or more serious adverse events.
The average length of ICU stay fell from 9.7 days among controls to 6.9 in the surgical group and overall hospital stay dropped from 18.1 days to 14.9 days, respectively.
“ICU stay in this particular disease is really important because about half the patients that survive the ICH event and make it to the hospital will die from ICU-related complications including pneumonia, sepsis, [pulmonary embolisms], [and deep vein thromboses],” Pradilla said. “So, every day that you are in the ICU that is compounded, it goes up and up.”
Exploratory analyses showed that mechanical ventilation was more common with surgery than with medical therapy alone (58.7% vs 52%) but that surgical patients spent fewer days on ventilation (5.3 vs 8.8).
In addition, 30 patients in the control group required decompressive hemicraniectomy compared with five in the surgical group, Padilla said.
‘A Welcome Finding’
Commenting on the findings for Medscape Medical News, Larry Goldstein, MD, Ruth L. Works Professor and chair of the Department of Neurology, University of Kentucky, Lexington said that “the benefit in functional outcome is a welcome finding in support of the intervention but is restricted to patients selected and treated as reflected in the study protocol with the benefit generally restricted to patients with more superficial bleeding rather than bleeding in deeper portions of the brain.”
Goldstein, who was not involved in the study, noted that of the 11,600 patients screened for eligibility, just 300 were randomly assigned. The accessors were also aware of the participants’ treatment group.
Goldstein pointed out that the intervention was not compared to other surgical techniques and was limited to patients who could have the procedure within 24 hours after onset of symptoms. “Whether the results would be similar using other techniques and whether more delayed interventions would be helpful is not known,” he said.
NICO Corp funded the trial. Pradilla disclosed research funding from the Acoustic Neuroma Association, the Emory Medical Care Foundation, and NICO Corp., and consulting work for Stryker and Aesculin. Goldstein reported no relevant conflicts of interest.