First Successful Trial in Intracerebral Hemorrhage: Lessons From ENRICH
Mark Bain, MD, a neurosurgeon at Cleveland Clinic’s Cerebrovascular Center, provided commentary on the ENRICH trial, a positive study of minimally invasive removal of intracerebral hemorrhage.
Mark Bain, MD, MS
Recently, investigators published the full data from the ENRICH trial (NCT02880878), a large-scale study evaluating NICO’s technology, BrainPath and Myriad, as a method of treatment for patients with intracerebral hemorrhage (ICH). The multicenter, randomized study included 300 patients with ICH who were randomly assigned 1:1 within 24 hours after the time last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control).
Patients in the study had either lobal (n = 208) or anterior basal ganglia (n = 92) hemorrhage. At 180 days, results showed that the trial was successful, with the surgery group demonstrating a mean utility-weighted modified Rankin scale (UWmRS) of 0.458 compared with 0.374 for those on medical management (difference, 0.084; 95% Bayesian credible interval, 0.005-0.163). This correlated to a posterior probability of superiority of 0.981, exceeding the 0.975 prespecified threshold superiority of surgery.
Additional data from the study showed a between-group difference of –0.013 (95% Bayesian credible interval, –0.147 to 0.116) on UWmRS among patients with hemorrhage in the anterior basal ganglia location and 0.127 (95% Bayesian credible interval, 0.035-0.219) among patients with hemorrhage in the lobar region. Within the surgery group, investigators recorded a mean percent reduction of 73.2 (±37.8) in hematoma volume from baseline to 24 hours, with a mean volume after the completion of surgery of 14.9 (±21.7) ml. Notably, nearly three-fourths (72.7%) of the patients in the surgery group had a volume of 15 ml or less after the completion of surgery.
Following the publication, study author Mark Bain, MD, a neurosurgeon at Cleveland Clinic’s Cerebrovascular Center, provided commentary on the positive results and what’s next for the field. He discussed the NICO technology in detail, its safety profile, and how it can be implemented going forward. In addition, he spoke on the specific differences in outcomes for those with hemorrhages located in lobar vs anterior basal ganglia regions and what these results might indicate.
NeurologyLive®: Of the results published, what stands out the most from a clinical perspective?
Mark Bain, MD: The biggest takeaway is that historically, trials that looked at operating on intracerebral hemorrhage weren't able to show functional benefit to patients. This is the first trial where we've shown that this type of a minimally invasive surgical approach helps patients and patients are better off functionally and recovering if they have surgery.
How does this technology from NICO operate? Is it feasible and easy to implement?
The technology is basically a surgical platform that is a minimally invasive operation in the brain. The way it works is that a very small tube is inserted in a special way where we're able to spare the nerve fibers in the brain. When you place it into the brain, it displaces the nerve fibers instead of transecting, the nerve fibers, and it allows us to access the parts of the brain, or even superficial parts of the brain, in a very minimally invasive way, in a way that doesn't cause any collateral damage.
The system is very easy to use. Most neurosurgeons can get the hang of this very quickly. In fact, it's used for other types of diseases, such as brain tumors, brain abscesses, and things like that. The surgical system also is a way to resect or remove the hemorrhage, so it's not just access. When you're working down this tube, there's a very small diameter, so you have to have specialty instruments. NICOs made this thing called the Myriad which allows you to finally aspirate the hematoma. There's this little chopper bit on it that allows you to break up the hematoma as well. You can very finely sort of shave out the hematoma and I think that makes a lot of sense. It helps the brain tissue because you can remove the units in a very gentle way and you can again, limit the collateral damage to the normal surrounding.
What does the safety profile look like for this technology?
That's one of the nice things. One of the secondary endpoints in the study was safety and safety events, which there was a very low rate of, including severe adverse events as well. Coming into the study, one of the things that we were concerned about with this minimally invasive way, is that after you remove the hemorrhage would it reaccumulate or would there be post operative rebleeding? I know that's always a concern for surgeons because they're using the spine. Some people say, “Well, maybe you can't see, or maybe you can't coagulate your hemostasis very well,” but the study showed that there was a very, very low rate of bleeding, and it was a safe procedure. That made us feel very good. As far as making the procedure safer, I think right now it is a very safe procedure. As the technology continues to develop, and we have better visualization, and specialty instruments that are made that improve surgery, the procedure is going to get even safer and safer.
How can we continue to build on this positive study?
it's a great question. A lot of people think ENRICH is the end, we finally have a positive trial and we’re done. We see this as the beginning. We finally have a positive trial, now we can build and get more trials. We need more trials, and certainly more trials are being planned right now. The area that we have the biggest interest in right now is basal ganglia group. If you remember in the trial, lobar hemorrhage drove the positive outcome. It’s pretty well proven now that if you remove the lobar hematoma, patients do better.
But when you go deep in the basal ganglia into the brain, what we noticed was that the signal was not as strong in those patients. A lot of people are saying that [outcome] was negative and it wasn't. There were many people in that trial that did very well with evacuation at those key areas but the signal was not as strong in the case of basal ganglia.
I think that's where we need to focus. If you think about it, hypertensive hemorrhage typically presents in these key areas and affects a lot of patients. We are really dissecting that area. Looking at the results of this trial, we need to figure out what our patient selection should be, and which of these patients are doing well, then we can form different trials down the road to address this. As we move forward, now that we have a positive trial and we're showing that this benefits patients, I think industry and companies are very interested in providing and developing specialized instruments to make our jobs easier to surgeons. That's going to translate into better patient safety and better efficacy of this procedure. I’m extremely excited about the future of this field, I think we're going to be able to help patients a lot better.
Transcript edited for clarity.
