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

Adam S. Arthur, MD, MPH1; Babak S. Jahromi, MD2; Paul S. Saphier, MD3,4et al

2025년 9월 2일

JAMA Neurol . September 2, 2025

DOI: 10.1001/jamaneurol.2025.3151

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

 Key Points

Question  Can minimally invasive surgery with the Artemis Neuro Evacuation Device improve outcomes in patients with spontaneous supratentorial intracerebral hemorrhage?

Findings  The MIND randomized clinical trial stopped early, given the positive results of a contemporaneous trial and the outcome of a subsequent feasibility analysis; however, the available data for 236 participants suggest that minimally invasive surgery (within 72 hours of symptom onset) did not improve 180-day disability or reduce 30-day mortality in patients with spontaneous supratentorial intracerebral hemorrhage compared to guideline-based medical management. Minimally invasive surgery significantly improved 30-day disability and reduced the occurrence of 180-day serious adverse events.

Meaning  While MIND did not demonstrate a benefit of minimally invasive surgery over medical management with respect to reducing 180-day disability or 30-day mortality, the Artemis system achieved efficient, safe, and substantial hemorrhage reduction in both deep and lobar bleeds.

Minimally Invasive Surgery vs Medical Management Alone for Intracerebral Hemorrhage

요약

·         중요성  자발성 천막상 뇌내출혈 환자에서 수술적 혈종 제거가 기능적 예후를 향상시키는지 여부는 여전히 명확하지 않다.

·         목적  Artemis Neuro Evacuation Device를 이용한 최소침습 수술(minimally invasive surgery, MIS)과 가이드라인에 기반한 표준 약물치료(medical management) 단독을 비교하여, 자발성 천막상 ICH 환자에서의 안전성(safety)과 효과(efficacy)를 평가하는 것이다.

·         연구 설계, 장소, 대상자 

-연구 디자인: 다기관, 공개형(open-label), 무작위배정 임상시험(RCT)

-무작위 배정 비율: 최소침습 수술군 : 약물치료군 = 2:1

-연구 기간: 2018년 2월 6일 ~ 2023년 8월 28일

-참여 기관: 전 세계 32개 센터

-분석 기간: 2024년 2월 ~ 2024년 9월

-대상자: 연령 18~80세

자발성 천막상 ICH (출혈량 20~80mL)

NIHSS 점수 ≥ 6

GCS 점수 5~15

-등록 환자 수: 4,066명 중 적합한 236명 최종 포함

최소침습 수술군: 154명

약물치료군: 82명

·         중재

-실험군: 증상 발현 후 72시간 이내 Artemis 장치를 이용한 최소침습 수술 + 표준 약물치료

-대조군: 표준 약물치료 단독

·         주요 평가변수 

-주효과(primary efficacy outcome): 180일째 사망 및 장애 정도 

→ mRS (modified Rankin Scale) 사용, 범위: 0 (증상 없음) ~ 6 (사망)

-주안전성(primary safety outcome): 30일 사망률

·         결과

-동시 진행 중이던 또 다른 ICH 임상시험에서 긍정적 결과가 발표됨에 따라, 독립적 검토 후 총 236명에서 조기 종료 결정

-대상자 특성:  중앙값 연령- 60세 (IQR 50~70)

여성- 36.9%

출혈 위치-심부출혈(deep hemorrhage): 69.5%

대뇌엽출혈(lobar hemorrhage): 30.5%

-180일 예후(Primary Efficacy Result)

  →MIS군이 약물치료군보다 우월하다는 근거 없음:

OR = 1.0395% CI = 0.62 ~ 1.72P = 0.45

보정모델에서도 유의하지 않음:OR = 1.1095% CI = 0.66 ~ 1.85P = 0.35

-30일 사망률(Primary Safety Result)

→ 30일 사망률 또한 두 그룹 간 통계적으로 유의한 차이 없음.

그룹	사망자 수	사망률	차이 (95% CI)
MIS군	11명	7.2%
약물치료군	8명	9.8%	-2.5% (95% CI: -11.7% ~ 4.8%)

·         결론 및 임상적 의미 

MIND 무작위 임상시험에서 증상 발현 후 72시간 이내 시행한 최소침습 수술(MIS)은표준 약물치료 단독과 비교했을 때

-30일 사망률을 유의하게 낮추지 못했으며

-180일 기능적 예후(장애 개선)에도 의미 있는 향상 효과 없음을 보여주었다.