2024 Top Story in Neurology: Stroke — The Early and Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH) Trial

Intracerebral hemorrhage (ICH) is a common and devastating event that often results in death or severe long-term disability, especially when the volume of hematoma exceeds 30 mL. Until the results of this trial¹ were published, the standard of care for the treatment of nontraumatic ICH was largely conservative; that is, the most recent American Heart Association guidelines for the treatment of spontaneous ICH recommend surgical evacuation of ICH via a conventional craniotomy only as a lifesaving treatment option based on most trials demonstrating no improvement in functional outcomes with surgery.² Although one trial of catheter-based evacuation combined with tissue plasminogen activator use showed a successful improvement of ICH, the treatment group did not have better functional outcomes (measured by the modified Rankin Scale [mRS]) at 1 year than the control group.³ Thus, a more effective intervention for ICH was urgently needed. The ENRICH trial was carried out to evaluate a different minimally invasive surgery for ICH evacuation. This procedure involves: 1) a small craniotomy and durotomy to expose the brain sulcus nearest to the hematoma; 2) identifying a trajectory to the ICH with imaging guidance using the BrainPath minimal access port; and 3) suction evacuation of the hematoma using the Myriad device. Both BrainPath and Myriad are FDA-cleared devices and are manufactured by NICO. NICO sponsored the trial but had no part in data collection or analysis or writing of the paper.

ENRICH was a prospective, multicenter, adaptive, randomized trial that enrolled 300 patients aged 18 to 80 years with a supratentorial, spontaneous ICH volume of 30 to 80 mL and moderate to severe neurologic deficits (indicated by the NIHSS) who could have surgery initiated within 24 hours after the last time known to be well. The exclusion criteria included the need for long-term anticoagulation, intraventricular hemorrhage involving more than 50% of either lateral ventricle, or a primary thalamic or infratentorial hemorrhage, among others. Initially, patients with ICH in both lobar locations (generally in the parietal, temporal, or frontal lobe) and anterior basal ganglia (caudate, putamen, and pallidum to the capsula externa) locations were enrolled. After 175 patients had been enrolled, enrollment criteria were adapted, according to the prespecified plan, such that only patients with lobar ICH were thereafter enrolled, because interim results for anterior basal ganglia ICH met the futility criterion for benefit of surgery. The control group received standardized conservative management based on the guidelines for the management of ICH from the American Heart Association and the American Stroke Association.

The prespecified primary endpoint for efficacy was the score on the utility-weighted mRS at 180 days. The mRS is a seven-point scale, with scores ranging from 0 (no symptoms) to 6 (death). The utility-weighted mRS assigns the following utility weights to each point on the scale: 1.0, 0.91, 0.76, 0.65, 0.33, 0.0, and 0.0 (such that higher scores indicate a better outcome). The primary endpoints for safety were death within 30 days of enrollment and the change in ICH volume on imaging. There were no significant differences between the surgery and control groups with respect to demographics, baseline ICH volume, the NIHSS score, the Glasgow Coma Scale score, time from last known well to randomization (median duration, 12.8 hours in the surgery group and 12.9 hours in the control group).

The results impressively favored surgery. The mean score on the utility-weighted mRS at 180 days was 0.458 in the surgery group and 0.374 in the control group, yielding a between-group difference of 0.084 (95% Bayesian credible interval, 0.005–0.163), with a posterior probability of superiority (0.981) that exceeded the 0.975 prespecified threshold to conclude that surgery was superior. Furthermore, the percentage of patients with a good outcome (traditional mRS score, 0–3) was 50.3% in the surgery group and 41.0% in the control group. In terms of safety, rescue decompressive hemicraniectomy was needed in 3.3% of patients in the surgery group and in 20% of patients in the control group. The rate of death within 30 days of enrollment was 9.3% in the surgery group and 18.0% in the control group. Serious adverse events occurred in 63.3% of patients in the surgery group and 78.7% of patients in the control group.

Although ICH remains a very serious and disabling condition, the ENRICH trial shows that a minimally invasive surgery using a suctioning device carefully inserted with imaging guidance within 24 hours of onset can result in better functional outcomes and lower fatality rates compared with conservative management. The benefit seems to be primarily in people with lobar ICH and was only evaluated in patients with an ICH volume of 30 to 80 mL. As with other recent interventions to improve outcomes in patients with stroke, we eagerly anticipate additional trials in the next several years with modifications in the devices, extension of the time window, and broadening of inclusion criteria.