(PS1) Late-Breaking Abstract Presentation: Efficacy and Safety of Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH): A Multi-Centered Randomized Adaptive Trial

Introduction: Supratentorial intracerebral hemorrhage (ICH) accounts for 10-15% of all strokes and results in significant morbidity and mortality. Standard of care involves supportive therapy to ameliorate secondary injury. Prior randomized controlled trials have suggested improved survival following minimally invasive clot evacuation. Indeed, there appears to be a relationship between greater clot reduction and improved outcomes. A conclusive advantage to surgical evacuation of supratentorial ICH over standard management has not previously been demonstrated.

Methods: The ENRICH Trial evaluated a Minimally Invasive trans-sulcal, Parafascicular Surgery (MIPS) approach using the BrainPath® and Myriad® devices (NICO Corporation, Indianapolis, IN). We conducted a multicenter, two-arm, randomized, Bayesian adaptive comparative-effectiveness study. Participants were block randomized by ICH location: anterior basal ganglia (ABG) or lobar, and index Glasgow Coma Score (GCS) to early ICH MIPS evacuation within 24 hours of last-known normal (LKN) plus standard guideline-based management versus standard medical management (MM) alone. The goal of the trial was to determine if MIPS evacuation results in improved outcomes, defined by the utility-weighted modified Rankin score (UWmRS) at 180
days. At pre-specified time points, the enrollment scheme could be adapted based on interim analyses to enrich the trial for hemorrhage location.

Results: Between December 1, 2016 and August 24, 2022, eligible patients were randomized to either MM or MIPS at 37 centers in the United States. Safety monitoring did not reveal meaningful differences between the MM and MIPS groups at any of the interim analyses and through the completion of the study. At the second interim analysis (175 enrolled), a pre-specified stopping criterion was met for the ABG location resulting in a study adaptation. Per design, the ABG location was halted and all subsequent participants were enrolled (enriched) meeting lobar location criteria. The trial randomized 300 participants, with 92 (30.7%) in the ABG location and 208 (69.3%) in the lobar location. There were no observed baseline differences between groups for age, ICH volume, GCS, or NIHSS. Overall mortality at 6 months was 21.3% (23.3% in the MM group and 20% in the MIPS group). In the MIPS group, median extent of hematoma evacuation was 87.7% with a median end-of-treatment volume (EOTV) of 7.2mL. Goal EOTV <15mL was reached in 72.7%. An mRS at 6 months was obtained in 286 participants (95.3%): 139 in the MM group (40 ABG and 99 lobar) and 147 in the MIPS group (47 ABG and 100 Lobar). The Bayesian primary analysis compared the mean UWmRS at 6 months between treatment groups, with an observed mean UWmRS of 0.374 for the control and 0.458 for the MIPS group, with a difference of 0.084. The estimated treatment effect was - 0.013 for the ABG location and 0.127 for the lobar location, with a combined treatment effect of 0.084 and the Bayesian posterior probability of superiority of the intervention was 0.9813, which exceeded the pre-specified 0.975 threshold to claim superiority of MIPS versus MM. The observed difference in mean UWmRS was -0.041 in the ABG location, 0.142 in the lobar location. Differences greater than 0 correspond to improved outcomes in the treatment group.

Conclusion : This is the first clinical trial to demonstrate functional benefit of surgical clot evacuation among participants with supratentorial ICH presenting within 24 hours of LKN. Specifically, MIPS was safe, resulted in substantial clot evacuation, and improved the UWmRS at 6 months relative to standard management. The overall benefit of MIPS appears to be from the strong positive effect observed for participants with lobar ICH.
Trial Registration: This study is registered with clinicaltrials.gov (NCT02880878)