ENRICH is a two-arm, multicenter, randomized, adaptive clinical trial assessing the effectiveness of minimally invasive trans-sulcal parafascicular surgery (MIPS) for intracerebral hemorrhage (ICH) evacuation. The trial results presented at the European Stroke Organisation Conference (ESOC) demonstrate a positive surgical outcome in the treatment of ICH. ENRICH represents the first positive surgical data in the treatment of ICH, serving as a catalyst for the revision of current guidelines and more informed treatment decisions for patients with ICH…

The exploration of the minimally invasive trans-sulcal parafascicular surgery (MIPS) approach for intracerebral hemorrhage (ICH) removal stems from the need to improve outcomes in patients with this devastating condition. Intracerebral hemorrhage is a serious condition associated with high mortality rates, poor functional outcomes, and substantial healthcare costs. ICH remains one of the only stroke subtypes to lack a definitive primary treatment, meaning practice varies significantly, and it is vulnerable to therapeutic nihilism. Traditional surgical techniques for ICH evacuation, such as open craniotomy and decompressive craniectomy, have been associated with significant invasiveness, morbidity, and mortality. Before the recent ENRICH trial, the evidence supporting the efficacy of surgical interventions for ICH removal was scarce and inconclusive. Several large-scale trials, such as STICH (Surgical Trial in Intracerebral Hemorrhage) and STICH II, failed to demonstrate a benefit of early surgical intervention in improving patient outcomes compared to best medical management.

These factors have prompted researchers to investigate less invasive alternatives to minimize tissue damage, reduce the risk of complications, and potentially improve patient outcomes. The MISTIE III trial (NCT01827046), published in 2019, assessed the efficacy and safety of minimally invasive catheter evacuation followed by thrombolysis, finding no improvement in the proportion of patients who achieved a good response at one year, compared to controls. Mortality rates, however, were significantly lower in the surgical intervention arm. As such, the 2022 American Heart Association (AHA) guidelines provide a Level 2a recommendation for the use of minimally invasive hematoma evacuation (Glasgow Coma Score (GCS) 5-12) to potentially reduce mortality.1 The level of evidence to support its impact on functional outcomes or performance compared to craniotomy is lower. The 2014 ESO guidelines state that there is no evidence to support the use of surgery on a routine basis to improve outcomes.2

Technological advancements have since led to the development of the MIPS approach, which involves using intra-operative image guidance, a tubular retractor, a high-definition exoscope, and a low-profile resection device for minimally invasive hematoma access and evacuation.3 Magnetic resonance imaging and diffusion tensor imaging are also used to guide trans-sulcal and parafascicular trajectories, to maximize tissue preservation. Given the support provided by the MISTIE trial for the benefit of clot reduction and early tissue preservation, the ENRICH (Early Minimally Invasive Removal of Intracerebral Hemorrhage; NCT02880878) trial was established to provide Level 1 evidence in the acute management of ICH.4

Experts Jonathan Ratcliff, MD, MPH, and Alex Hall, DHSc, MS, RN, who led the ENRICH trial in the United States, aimed to evaluate the efficacy of the MIPS approach using the BrainPath® and Myriad® devices for safe access to deep brain structures and early evacuation of supratentorial ICH (within 24 hours of symptom onset).4 The trial employed a randomized, adaptive, comparative-effectiveness design. Inclusion criteria covered patients aged 18-80, with an ICH volume between 30-80ml and a GCS of 5-14.3 Patients were block randomized based on ICH location (anterior basal ganglia vs. lobar location) and GCS into either early ICH evacuation using MIPS plus standard guideline-based management or standard management alone. The primary endpoint was improved outcomes, defined by the utility-weighted modified Rankin score (uW-mRS) at 180 days, with secondary endpoints including clinical and economic outcomes measured at 30, 90, 120, and 180 days.

The ENRICH trial enrolled a total of 300 patients. After the first 175 patients, only the lobar population was enrolled, based on pre-specified permitted enrichment.5 Baseline characteristics, including age, sex, race, modified Rankin scale, hemorrhage volume, and index GCS were evenly distributed across both groups.6

“This is the first trial to demonstrate functional benefit in surgical clot evacuation among patients with supratentorial ICH. As we continue to understand the data collected in the ENRICH trial, we are excited at the possibilities and future ICH management.” – Alex Hall, DHSc, MS, RN, Emory University School of Medicine and ENRICH study investigator.4

The primary results of the ENRICH trial presented by Jonathan Ratcliff and Alex Hall at ESOC 2023, demonstrated a Bayesian posterior probability of superiority of 0.9813, indicating the superiority of MIPS over standard guideline-based medical management for improving outcomes of patients with ICH.5 This exceeded the predefined threshold of superiority of 0.975. Mean uW-mRS at 180 days was 0.458 for the MIPS group versus 0.374 for the medical management group. However, the posterior probability of superiority for the anterior basal ganglia location was 0.43, suggesting a lack of efficacy in this specific subgroup, and a stronger indication that the lobar location was driving the overall combined effect. Overall, the MIPS surgical approach successfully removed 87.7% of blood volume, and the greater the hemorrhage reduction, the better the outcome.6 Additionally, the ENRICH trial demonstrated favorable outcomes, including a 2.6-day reduction in ICU stay and total hospital stay for the surgical group compared to the medical management group. The number needed to treat to prevent an mRS score of 3-6 was eight patients, highlighting the potential impact of the MIPS approach. 6

The results of the ENRICH trial represent a significant advancement in the field of ICH management. With no previous randomized controlled study demonstrating the benefit of early evacuation, the ENRICH trial provides Level 1 evidence to guide clinicians in making treatment decisions for patients with ICH. The promising outcomes observed in the trial suggest that MIPS may offer a viable treatment option for patients with supratentorial ICH, particularly in lobar location hemorrhages, and by employing these approaches, surgeons can potentially achieve better functional outcomes for patients. However, questions remain regarding the applicability of the MIPS approach to deeper hemorrhages and basal ganglia location.

“We would not be able to have trial success without our wonderful sponsor and 37 centers who delivered a great standard of care” – Jonathan Ratcliff, MD, MPH, Emory University School of Medicine and ENRICH study investigator.4

Written by Ailish Gregory

Reviewed by Juliet Lawrence


  1. Greenberg SM, Ziai WC, Cordonnier C, et al. 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline from the American Heart Association/American Stroke Association. Stroke. May 2022; 53(7):e282-e361.
  2. Steiner T, Salman RA-S, Beer R, et al. European Stroke Organisation (ESO) Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Int J Stroke. Oct 2014;9(7):840-855.
  3. Rennert RC, Khani M, Thomas K, et al. Transsulcal parafascicular brain path-assisted approach to subcortical lesions: 2-dimensional operative video. Surg Neurol Int. Mar 2021; 12:107.
  4. Ratcliff JJ, Hall AJ, Porto E, et al. Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH): Study protocol for a multi-centered two-arm randomized adaptive trial. Front Neurol. 2023 Mar 16;14:1126958
  5. Hall A, et al. Very early minimally invasive removal of intracerebral hemorrhage: the ENIRCH trial. [Press Release]. Presented at the European Stroke Organisation Conference; 25 May 2023; Munich, Germany.
  6. Hall A, Ratcliff JJ. ENRICH trial: early surgical intervention in intracerebral hemorrhage. [Interview with VJNeurology]. May 2023.