Trial to weigh different treatments of TBI

Host Amber Smith: Upstate Medical University in Syracuse, New York, invites you to be The Informed Patient, with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith.

Upstate was chosen to participate in a national $32 million multi-institutional clinical trial to improve patient outcomes after severe traumatic brain injury. Here to explain how the study will work is Dr. Devin Burke. He's an assistant professor of neurology at Upstate.

Welcome to "The Informed Patient," Dr. Burke.

Devin Burke, MD: Thank you, Amber. It's great to be here. I'm very excited to talk more about the trial.

Host Amber Smith: Now, this trial, this study, is paid for by the National Institutes of Health. In addition to Upstate, how many other institutions are participating?

Devin Burke, MD: So it's a multi-center trial. There's about 50 sites around the country. These sites are all. Level 1 trauma centers like Upstate Medical University, and sites that see a large volume of severe traumatic brain injury, just like Upstate.

Host Amber Smith: What does Level 1 trauma center mean? Can you explain why that's an important designation for patients with TBI?

Devin Burke, MD: A Level 1 trauma center is a health care system that specializes in the management and resuscitation of very sick trauma patients. In order to be a Level 1 trauma center, you need availability of multiple specialists on call and also have some capabilities such as urgent intervention, burn intervention and things like that.

Host Amber Smith: So when does this study start, and how long does it last?

Devin Burke, MD: We're in the process of submitting our IRB, which is an Institutional Review Board document, and once that's approved by the study site or the countrywide study, then we're hoping to start enrolling patients as soon as possible.

Part of our approval for the IRB is making sure we do enough due diligence to spread word about that we're doing this trial that is soon coming to the Syracuse community.

Host Amber Smith: Well, let's talk about the scope of the problem of traumatic brain injuries. About how many people come to Upstate with traumatic brain injuries every year?

Devin Burke, MD: Traumatic brain injury is a very common disorder and even more common in certain age groups, age groups that are mobile, driving vehicles; elderly population that is susceptible to falls; and those that are in high-risk activities, such as cycling, motorcycling, contact sports, and things like that. Of those that get a traumatic brain injury, a severe traumatic brain injury, which is the patient population that we're looking in, in this trial, is a little more rare.

I would say Upstate as a whole sees about 100 people per year with a severe traumatic brain injury, so that is the patient population that we are going to be focusing on for this trial.

Host Amber Smith: How do you define severe traumatic brain injury, as opposed to regular traumatic brain injury?

Devin Burke, MD: Severe traumatic brain injury, or the categories of brain injury, are usually defined by the examination on arrival, so people who have a severe traumatic brain injury are usually comatose, not following commands and likely requiring mechanical ventilation to provide their body with enough oxygen.

So these are very sick, comatose patients who have a traumatic brain injury.

Host Amber Smith: And I know it's individual, based on the patient, but in general, what is the prognosis for someone who has a severe traumatic brain injury?

Devin Burke, MD: It is certainly the most morbid type of brain injury.

I would say about 30% to 40% of people with severe traumatic brain injuries, those in a coma, those who are not waking up, will die in about six months. Of those patients that survive, which can be about 60%, a lot of them suffer lifelong disability, about 80% suffer lifelong disability.

Your outcome depends upon age, medical conditions prior to the traumatic brain injury and also, what we hope, is what we do here in the ICU and operating rooms, and things like that. So it's a large problem, a very common disease that is very serious and morbid.

In our minds, this is the perfect kind of disease to try to do more research to provide better care for our patients.

Host Amber Smith: I wanted to ask you what sorts of procedures might be required for these patients during their hospitalization?

Devin Burke, MD: The trial itself involves a couple of procedures.

One of the procedures that's done after you have a traumatic brain injury, one of the predictors of how you will do, is basically how high the pressure is in your brain after you hit your head, and it can swell just like any bruises or any injury. The brain is a little different because there's no room for your injury to swell, so you can have increased pressure inside your brain.

One procedure that we'll do in an injury this severe is to place a monitor intracranially (within the skull) to continuously measure the pressure inside the brain. We have certain parameters that we like to keep it below and keeping it below those certain parameters has shown to improve outcome in prior studies.

With this trial, there's another monitor that we can place inside the brain that measures the oxygen present inside the brain, and that is a thing that we've actually done here at Upstate for a number of years. But there has never been any high-quality, randomized controlled data to support this practice.

That is really the crux of the research that we're doing, is to look at outcome with the brain pressure monitor versus the brain pressure monitor and the oxygen monitor. These are the two groups that we're going to look at and see if one group does better or worse.

Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith.

I'm talking with neurologist Dr. Devin Burke about a new study designed to improve patient outcomes after severe traumatic brain injury.

So the patients who are part of the study, how will they be able to give consent to be in the study if they're comatose with a traumatic brain injury?

Devin Burke, MD: That is an excellent question, and that is one of the things that makes our trial unique.

So when you have a disease such as this, that really the patients with severe traumatic brain injury are unconscious and unwilling or unable to give their consent, the government passed a law in the '90s to try to remedy this conflict. You have these diseases, such as traumatic brain injury or other emergent diseases, that require high-quality research, but you have the problem that the patients that would be enrolled are too sick to be awake or to give consent.

To remedy this conflict, the FDA (Food and Drug Administration) passed a law (technically, it created an exception) called the Exemption from Informed Consent Act. This is designed to try to improve the quality of research done in patients with emergent illness. It comes with a lot of specifiers and a lot of requirements because what we're asking for is to enroll a patient into a trial without their consent, so that's a pretty serious venture. So the things that it requires you to do is to, one, consult the community as a whole. Let them know that this trial is being performed, and to solicit their input and their thoughts and opinions, and really to reach all sorts of demographics within the community.

The youth -- we went up to Syracuse University, we talked to the Neuroscience Club up there and got their opinions, because the youth, that is a population that is at high risk of traumatic brain injury.

We've also talked to elderly populations and received their opinions on the ethics of this trial. We're required to do six of these events, and we've completed all these, which is great.

The second thing that we're required to do is public disclosure events, to disclose that this is a trial we will be performing, and give people advance notice. Some things we've done are certain press releases, and really, this podcast helps as well. "The Informed Patient" plays an essential role in disseminating this important information. We thank you for that.

Host Amber Smith: Well, you said, or you described, that you'll be comparing this test for the intracranial pressure, with the intracranial pressure test and the brain tissue oxygenation test. You as a practitioner, do you have kind of a gut feeling of which one you think is going to be a better way to determine which patients are going to do well?

Devin Burke, MD: Here at Upstate University, in the department of neurocritical care, we have been placing the intracranial oxygen catheters for a while. That's on some lower-level evidence, some retrospective studies, some correlatory studies, some animal studies that showed that increasing the oxygen or monitoring the amount of oxygen in the brain can possibly lead to a better outcome, so we hope that that is the case.

It also gives us another tool to try to optimize this disorder that has such high morbidity and mortality (sickness and death). However, in order for a trial to be done, there needs to be a panel that decides that one is not better than the other. We call this principle "equipoise." In order to perform a trial, it has to be truly unclear what treatment is better, because in this trial, we are going to be treating patients with intracranial pressure monitoring alone, so it has to be clear in the evidence that there is a gap and there is not a certain answer, but obviously, we're hoping that we can have some more tools to treat these patients.

Host Amber Smith: Well, please walk us through how this is going to happen practically. When the trial begins, and a patient arrives in the emergency department with a traumatic brain injury, what happens then?

Do they call you?

Devin Burke, MD:

I want to emphasize it takes a village. This is a multidisciplinary venture. So, the first people other than the EMTs (emergency medical technicians) that the patient will see is the, emergency physician and emergency team. So the emergency team will usually alert trauma surgeons that there is a trauma coming in, and if the trauma potentially involves the brain, and there's a threat of a severe traumatic brain injury, neurosurgery will be alerted as well. And our trauma and emergency team will both assess the patient for any life-threatening injuries that require resuscitation, and then we will start to consider the patient for the trial.

So there'll be some criteria. The criteria will be mainly around what does the examination look like? Is the patient comatose, and if so, then we would hope that our emergency and trauma colleagues alert our research team. We'll come down to evaluate the patient for enrollment in the trial.

It's the easier end because truly what we're doing in the trial is very similar to what we do on a daily basis. It's not really changing much. It's just incorporating these patients in a more systematic way to evaluate if the treatments that we do, if they help or not.

Host Amber Smith: Some of these patients will have more than just a traumatic brain injury. They'll have other injuries as well. Are they still able to be in the trial if they're having their other injuries taken care of before?

Devin Burke, MD: Yeah, most of them will. We are always in close consultation with our trauma team to evaluate the safety of enrolling in the trial.

If the other injuries are not too life-threatening, then yeah, sure, they can be enrolled in the trial. However, If there are urgent surgical emergencies that need to be taken care of prior to treatment or monitoring of the severe traumatic brain injury, then those will be taken care of at that time, and the patient will probably likely, not be enrolled in the trial. So always, the life-threatening issues take precedence.

Host Amber Smith: How do you decide which arm of the trial the patient will be in? Either the one where they're just getting the intracranial pressure, or ...

Devin Burke, MD: Yeah, so it's a randomized trial, so once the patient has met criteria for inclusion, the information will be sent to our central hub, and the computer will randomize to one treatment strategy versus the other. So the clinican, and nursing at bedside, won't really know at the time what group the patient gets assigned to.

Host Amber Smith: And they'll stay in the same arm the whole time they're in the hospital, right? That's kind of the whole point.

Devin Burke, MD: That's exactly right. Yeah.

Host Amber Smith: Well, I appreciate you making time to tell us about this, Dr. Burke.

Devin Burke, MD: Of course. I'm happy to talk about it. Traumatic brain injury is a passion of mine, and we truly need better options out there. And there's such a need for research, and we're happy to be on the cutting edge here at Upstate in the neuro ICU. And I just want to shout out to all the nurses in the Neurocritical Care Unit that work hard every day to provide good care to our patients. And thank you so much.

Host Amber Smith: My guest has been assistant professor of neurology Dr. Devin Burke.

"The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe.

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