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. 2025 Sep 2:e253151.
doi: 10.1001/jamaneurol.2025.3151. Online ahead of print.

Minimally Invasive Surgery vs Medical Management Alone for Intracerebral Hemorrhage: The MIND Randomized Clinical Trial

Adam S Arthur  1 , Babak S Jahromi  2 , Paul S Saphier  3   4 , Christopher M Nickele  1 , Robert W Ryan  5 , Peter Vajkoczy  6 , Clemens M Schirmer  7 , Christopher P Kellner  8 , Charles C Matouk  9 , Eric J Arias  10 , Jamie S Ullman  11 , Michael R Levitt  12 , Ziad A Hage  13 , David J Fiorella  14 ; MIND Study Investigators and Collaborators
Collaborators, Affiliations

Minimally Invasive Surgery vs Medical Management Alone for Intracerebral Hemorrhage: The MIND Randomized Clinical Trial

Adam S Arthur et al. JAMA Neurol. .

Abstract

Importance: It remains uncertain whether surgical evacuation improves functional outcomes in patients with supratentorial intracerebral hemorrhage (ICH).

Objective: To compare the safety and efficacy of minimally invasive surgery with the Artemis Neuro Evacuation Device to guideline-based medical management alone for spontaneous supratentorial ICH.

Design, setting, and participants: The MIND open-label, multicenter randomized clinical trial randomized patients with spontaneous supratentorial ICH in a 2:1 ratio to either minimally invasive surgery or medical management alone. Participants were enrolled at 32 participating global sites between February 6, 2018, and August 28, 2023. This article reports on the primary trial outcome. Of 4066 eligible adult patients (aged 18-80 years) with moderate- to large-volume supratentorial ICH (20-80 mL), baseline National Institutes of Health Stroke Scale score of 6 or higher, and Glasgow Coma Scale score between 5 and 15, 154 were randomized to minimally invasive surgery and 82 to medical management. Data were analyzed from February to September 2024.

Intervention: Minimally invasive surgery (within 72 hours of symptom onset) plus medical management or medical management alone.

Main outcomes and measures: The primary efficacy outcome was 180-day combined death and disability via ordinal modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]). The primary safety outcome was 30-day mortality.

Results: Following an independent feasibility analysis prompted by the publication of positive results of a contemporaneous ICH trial, enrollment was stopped early at 236 participants. Overall median (IQR) participant age was 60 (50-70) years, 87 participants (36.9%) were female, 164 (69.5%) had primarily deep bleeds, and 72 (30.5%) had primarily lobar bleeds. Efficacy results of the primary model analysis suggested lack of evidence for the superiority of minimally invasive surgery over medical management (odds ratio [OR], 1.03; 96% CI, 0.62-1.72; P = .45). The adjusted model's mean OR was also nonsignificantly greater than 1 (OR, 1.10; 96% CI, 0.66-1.85; P = .35). By 30 days, 11 participants (7.2%) in the surgery group and 8 (9.8%) in the medical management group died (difference, -2.5%; 95% CI, -11.7% to 4.8%).

Conclusions and relevance: In the MIND randomized clinical trial, minimally invasive surgery within 72 hours did not significantly reduce 30-day mortality or improve 180-day disability in patients with supratentorial ICH compared to medical management alone.

Trial registration: ClinicalTrials.gov Identifier: NCT03342664.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Arthur reported personal fees from Penumbra during the conduct of the study and holding equity in inTRAvent outside the submitted work. Dr Jahromi reported grants from Penumbra during the conduct of the study. Dr Nickele reported stock ownership in Neuroventx outside the submitted work. Dr Schirmer reported grants from Penumbra during the conduct of the study; grants from Balt, Cerenovus, Medtronic, Microvention, MIVI Neuroscience, Route 92 Medical, Stryker, and the US National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS); personal fees from Balt, Medtronic, Microvention, Stryker, and Werfen; and ownership of NTI/REIST (venture capital funds focused on medical technology) outside the submitted work. Dr Kellner reported grants from Integra and Penumbra and serving as founder of Borealis outside the submitted work. Dr Matouk reported personal fees from Penumbra, Silk Road, and Terumo MicroVention; holding equity interest in Jiva Medical; and grants from CereVasc for serving as national principal investigator of the STRIDE trial outside the submitted work. Dr Arias reported personal fees from Penumbra outside the submitted work. Dr Ullman reported patient enrollment payments sent to the Feinstein Institute of Medical Research of Northwell Health from Penumbra during the conduct of the study. Dr Levitt reported grants from Medtronic and Stryker; holding equity interest in Apertur, Fluid Biomed, Hyperion Surgical, Proprio, Stroke Diagnostics, and Synchron; consultant fees from Aeaean Advisers, Arsenal Medical, Genomadix, and Stereotaxis; and serving as an advisor for METIS Innovative, on the editorial board for the Journal of NeuroInterventional Surgery, and on a data safety monitoring board for Arsenal Medical outside the submitted work. Dr Hage reported consulting or speaker fees from Balt, Medtronic, and Stryker outside the submitted work. Dr Fiorella reported grants from SUNY Stony Brook for serving in a principal investigator role in study during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Screening, Allocation, Follow-Up, and Analysis
The intention-to-treat population comprised all randomized participants. The per-protocol population included participants who received the allocated treatment without inclusion or exclusion violations. The as-treated population comprised participants according to the actual treatment received. Randomization schedule violations occurred in 4 participants (these included 2 treatment crossovers). aOne participant was randomized to minimally invasive surgery (MIS) but received medical management (MM) treatment. This participant was analyzed as MIS in the intent-to-treat (ITT) population and MM in the as-treated (AT) population. bAnother participant was randomized to MM but received MIS treatment. This participant was analyzed as MM in the ITT population and MIS in the AT population. Two more participants were randomized to MIS but withdrew consent before MIS treatment. These participants were analyzed as MIS in the ITT analysis and excluded from the AT analysis.
Figure 2.
Figure 2.. Forest Plot: Ordinal Modified Rankin Scale (mRS) Scores
A, Primary efficacy outcome (ordinal mRS at 180 days) for intention-to-treat (ITT) and per-protocol (PP) populations analyzed using primary and secondary models. B, Ordinal mRS at 30, 90, and 180 days for the PP population (overall, deep, and lobar cohorts) adjusted for baseline monitored Hemphill score and intracerebral hemorrhage location. Data in panels A and B are shown as the odds ratios (ORs) for minimally invasive surgery (MIS) vs medical management (MM). Note that the pronounced treatment benefit of MIS at 30 days diminished by 90- and 180-day follow-up. Missing values (or data collected outside the protocol window) were imputed by a posterior median from a longitudinal model.
See this image and copyright information in PMC

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