The summary of ‘ENRICH trial: early surgical intervention in intracerebral hemorrhage’

00:00:00

In this part of the video, Alex Hall introduces himself as an assistant professor in emergency medicine at EM University and a leader of the enriched clinical trial scientific team. He, along with Dr. Jonathan Ratcliffe and Dr. Gustavo Pria, who are the lead investigators in neurocritical care and surgery respectively, discuss the design and execution of the enriched trial aimed at evaluating minimally invasive evacuation of intracerebral hemorrhages. They focused on patients with hemorrhages in the lobar and basal ganglia regions to determine the benefits based on the 180-day modified Rankin scale. The study employed a randomized approach to compare medical management with a standardized surgical procedure using frameless stereotactic neuronavigation to guide the least disruptive trajectories for clot access, respecting the subcortical white matter.

00:03:00

In this part of the video, it explains the use of specialized surgical technologies in brain surgery. The “Brain Path” device, which is tubular and has a small footprint, is highlighted for providing access and visualization while minimizing brain trauma. An automated resection tool is used to efficiently suction and remove clots, and exoscopic visualization with high-resolution cameras enhances the surgical environment. The procedure aimed to intervene within 24 hours, ideally within 8 hours, of the patient’s last known normal state. Conducted across 37 US centers, the trial compared routine medical management with surgical management using these technologies. It was a multicenter, randomized, and adaptive trial intended to provide clinical evidence of functional benefits and ensure safety. Patients were block-randomized based on their initial index GCS and location, with a planned sample size of 150-300 patients and interim analyses after every 25 patients to determine whether to continue the study.

00:06:00

In this part of the video, the speaker explains the inclusion criteria and key details of a clinical trial. The trial included patients aged 18-80 with a primary spontaneous intracerebral hemorrhage (ICH), a Glasgow Coma Scale (GCS) score between 5 and 14, and a hemorrhage volume between 30 and 80 cc. Key exclusion criteria were secondary causes of hemorrhage, very low NIH Stroke Scale scores, significant ventricular hemorrhage, herniation, brain stem findings, and uncontrollable coagulopathies. The primary efficacy endpoint was the modified Rankin Scale (mRS) score at 180 days, analyzed using Bayesian methods with a success threshold of a posterior probability greater than 97.5%. An independent neuropsychologist adjudicated the mRS outcomes using blinded audio recordings. Out of over 11,000 screened patients, 300 were randomized into the trial, with 150 in the intervention group and 150 in the medical management group. The mean age was 62 in the intervention group and 61 in the medical management group, with balanced baseline characteristics. The primary endpoint showed a positive treatment effect in both the overall and the lobar ICH subgroup.

00:09:00

In this part of the video, the speakers discuss their findings presented at ESO regarding the efficacy of a procedure. They highlight the MRSS at different time points, showing statistically significant protective effects, including reduced deaths and improved outcomes from removing blood. The analysis focused on 7-day, 30-day, and 90-day time points and indicated early positive effects. Additionally, the procedure efficiently removed blood, with a median treatment volume of about 7 mL. Greater hemorrhage removal correlated with better patient outcomes. Comparatively, the death rate at 30 days was significantly lower in the treatment group (9.3% vs. 18.1%). The ICU and overall hospital stays were also reduced by 2.6 and over 2 days, respectively, favoring the treatment group.

00:12:00

In this part of the video, the speakers discuss the biological plausibility and positive effects observed in patients following surgical interventions. They acknowledge that they are not the first to consider surgery beneficial for certain conditions and credit advancements in technology, clinical trial design, and patient selection for their progress. The enriched trial is highlighted as the first to demonstrate functional benefits of surgical clot evacuation, despite previous studies like Stitch and Misty indicating promising signals. They note that while there were clear benefits for some patients, particularly with hemorrhages, certain aspects, such as the basal ganglia location, require further study. Current analysis focuses on refining patient populations based on factors like timing and volume parameters.

00:15:00

In this segment, the discussion centers on the tolerance levels of patients with brain atrophy versus basal ganglia patients in relation to upper range limits for treatment volumes. Specifically, older patients can often tolerate higher volumes (up to 100 cc’s) without severe consequences, whereas basal ganglia patients struggle with 80 cc’s due to different anatomical impacts, especially on the internal capsule and motor fibers affecting motor recovery. Special measures are suggested for basal ganglia patients to assess the impact on motor and speech functions, and for those with behavioral challenges. The segment also notes an important distinction between newer techniques and those used in the MISTIE study, highlighting the inclusion of patients with active bleeding (positive spot sign) in newer methods. These methods allow for effective management of active bleeding, unlike MISTIE, which excluded such patients. The ability to achieve hemostasis during endoscopic evacuation is also discussed, with ongoing studies considering these factors for treatment refinement.

00:18:00

In this segment, the speaker discusses the methodology and results of a trial involving thalamic hemorrhages and their recovery timelines. Thalamic hemorrhages often result in longer patient intubation and ICU stays, leading to prolonged recovery to achieve comparable outcomes, which is why they were excluded from this particular study. The study used FDA-cleared devices typically employed in various neurosurgical procedures, indicating their reliability and wide applicability.

The trial’s scope included 37 sites consisting of leading academic institutions and community hospitals. The procedure was well-executed across these varied settings, demonstrating that with appropriate training and technology, such surgeries can be performed effectively even in community hospitals, not just tertiary care centers. This accessibility is crucial for treating various cerebrovascular pathologies.

00:21:00

In this segment of the video, the speakers discuss the importance of early intervention in improving survival and neurological outcomes for patients with intracerebral hemorrhage. They highlight that quicker intervention can lead to fewer adverse events and shorter hospital stays. They also mention that a significant number of diverse surgeons participated in the trial, indicating the technique’s broad applicability. There is anticipation for updated guidelines from the American Stroke Association based on the trial’s results. Additionally, the discussion touches on the potential of a general minimally invasive approach as opposed to being device-specific, referencing past trials and their outcomes for context.

00:24:00

In this part of the video, the speakers discuss the benefits of an integrated approach and the emergence of newer surgical devices that respect white matter structures while providing the necessary surgical tools. They highlight that minimally invasive surgery has been proven superior to conventional surgery based on the first rigorous trials. The conversation then shifts to the continual improvement of medical devices, drawing parallels to advancements seen in thrombectomy technologies. The speakers emphasize the role of industry leaders in driving innovation, underscoring a partnership between academia and industry, specifically mentioning the ni Corporation’s support and trust throughout a challenging seven-year trial period, including the COVID-19 pandemic.