Joey Wahler (Host): It's taking part in an important national study regarding patients suffering significant blood loss. So, we're discussing Mount Carmel Health System's Trauma Program. Our guests, Andy Betz, he's Trauma Program Manager; Dr. Chance Spalding, a trauma surgeon; and Dr. Paul Zeeb, EMS Medical Director, all with Carmel Health System. 

This is Wellness In Reach, a Mount Carmel podcast. Thanks so much for joining us. I'm Joey Wahler. Gentlemen, welcome. Appreciate the time.

Chance Spalding, MD: Thank you. Thanks

Andy Betz, RN, CNP: Thanks, Joey.

Host: Absolutely. Great to have you aboard. So first for you, Andy, what in a nutshell is the role of clinical trials in advancing medical treatments and why is participation so important for patients and really society at large before we get into this one specifically?

Andy Betz, RN, CNP: Great question and really important within the trauma umbrella of healthcare as well. Pretty much all of the medical information that we get comes from human studies. And most everything considered as standard of care today in medicine has really been shaped by rigorous clinical research along with empirical evidence.

And the process involves conducting trials, making observations, determining the most effective at treatments and practices, and then building on that from previous research. And trauma continues to be a major cause of death and disability in the United States. The economic and human impact is huge. And specifically with hemorrhagic shock and blood loss and trauma, it's one of the places that we have the opportunity to continue to impact the outcomes of these patients. And the trauma care really begins in the field. And that's where this trial comes in allowing us to bring some of those advances to the patients in the field.

Host: And so, that specific study we're discussing here, it's known as the CAVALIER study. And Dr. Spalding, CAVALIER is an acronym. So, maybe you could first please tell us what it stands for and what are its significance and goals of this study in treating trauma patients?

Chance Spalding, MD: So, CAVALIER is about advancing care with calcium and vasopressin into the field further at the point almost of injury of patients. It is a multi-institutional trial that's performed by something called the LITES Network, which is Linking Investigations in Trauma and emergency services. So, it's a large network of hospitals that we're joining together to go through and answer significant questions that are going to impact those who are injured. Hopefully, it's not us, but we can just as likely be injured as anybody else.

And the point of it is we have some treatments that we're doing like calcium and vasopressin to go through. And we do use these on a daily, if not weekly basis in the hospital. But the real question becomes, well, what would happen if we took these treatments and we gave them to patients very early when they're injured? Could we go through and improve their outcomes? And the only way to answer that question is to start to do the work and partner with our emergency medicine services team, which is you know, a lot where Dr. Zeeb has come in to go through and help this trial get really advanced and off the ground in Columbus.

Host: And so, speaking of Dr. Zeeb, as Dr. Spalding mentioned there calcium and vasopressin, they account for the C and the V in CAVALIER, if you will. Dr. Zeeb, how do they function in the management of trauma patients that have suffered a lot of blood loss?

Paul Zeeb, MD: Calcium is vitally important in terms of neurologic function, blood clotting, and cardiac function or heart function. Victims of trauma can have a calcium deficiency. And once we start transfusing blood, it can make the calcium deficiency worse. There are chemicals in stored blood that are used to keep the blood from clotting. Those chemicals will eat up or bind to our calcium in our system. So if a patient's going to receive a massive transfusion of blood products, we routinely add calcium to their treatment plan. So, the question is, if we use calcium in the pre-hospital arena, which we already plan on using in the hospital. If we use it sooner, will it make a difference in terms of patients' ability to clot and in terms of how they respond to the transfusions they give them?

So, calcium's already part of our treatment plan. We use it commonly in medicine. The question is, if we use it sooner in trauma patients, will we see positive benefit? Vasopressin we use not so much in the pre-hospital arena, but in the hospital to support blood pressure and perfusion of the brain, heart, and other essential organs. And the question with vasopressin is if patients receive it sooner or as part of routine trauma care in the trauma bay, or shortly after admission, if there's an improvement in patient outcome, particularly survival to hospital discharge. So, that's why we're linking these two medications. As part of the study, patients could receive calcium alone or they could receive vasopressin alone or both.

Host: And so, piggybacking on that, Dr. Spalding, why is the timing of administering calcium and vasopressin in this CAVALIER study, why is that so significant and what are the potential impacts that administering them earlier could actually have on patients?

Chance Spalding, MD: Joey, that's a really good question. So, one of the things that's interesting is what we do in the time that we care for patients isn't very well known. We do know when someone's bleeding, we have about an hour to go through and do everything we can to save their life.

And oftentimes, we receive patients from the scene within that timeframe. And so, we can go through and start to do some work. But what we don't know is if we start to have some of those life-saving treatments started earlier in the care of that patient, and we start to go through and administer some of those medications. So, calcium's a perfect example. So if we give somebody calcium, the question is if you're in a car crash and you get injured and you're bleeding, if we give you calcium at that moment, can we start to increase your ability to form a blood clot? Can we make your heart pump stronger? Can we give you better neurological function when you recover? And vasopressin is very similar. Can we increase the amount of blood pressure you have to preserve neurologic function with your brain as you're coming to the hospital, as you're in the hospital. So when you do recover from your trauma, you'll have better outcomes. And so, these are really the questions, is can we move the lifesaving care that we typically do in the hospital? Can we put that in the field closer to the point of injury and have our great paramedics and our EMS teams be starting to do that care? So when they come to us, we're kind of prepared and everyone can go through and transition that care to us. Hopefully that answers that question.

Host: Absolutely. And I think before we go any further, Andy, for you, I think it would be interesting to get your take on what it means to the trauma program there to be involved in a study like this that really could literally be the difference between life and death, right?

Andy Betz, RN, CNP: Yeah, I'm really excited to do this in addition to some other exciting things that we're doing here at Mount Carmel as a trauma program to be included in multicenter trials like this. The leadership here within the Mount Carmel system is very forward-thinking about allowing us to be innovative with both the things that we want to try as a trauma program, new equipment, you know, taking part in research like this, being aggressive about going out there, and locating these kinds of innovative things that are happening within the trauma realm across the country. And being that kind of local anchor for national research that's happening for us here in central Ohio for the trauma patients that we care for.

And it 's very important to me as the program manager to continue to grow our program within the health system. But also, most importantly, to get potentially lifesaving things to the patients in the field to empower our emergency medicine partners and our pre-hospital partners to practice at the greatest extent of their licenses and abilities. And embracing that partnership that we have with our EMS and pre-hospital partners is really important to us and ultimately affects the care of the patients that we take care of, and that's probably the most important thing.

Host: Absolutely. And Dr. Zeeb, how about compared to other studies, how is emergency and trauma research different when it comes to things like patient consent and enrollment here?

Paul Zeeb, MD: This study is a double-blinded randomized study, meaning we don't know if the patient's getting the real drug or a placebo, salt water. And we're doing it for patients who are critically ill. All human research is governed by the federal government and we are expected to provide public notice and do other things in order to meet the standards for any research that does not allow patient consent. So if a patient's critically ill as the consequence of trauma, our priorities really have to do with managing the bleeding, getting them the care they need, and we don't have oftentime an opportunity to actually get an appropriate informed consent. So, this study is considered exempt from informed consent, which means we have to follow the federal standards, public notification, the ability for patients to opt out, the ability for patients to receive additional information, all those things are important about the study. The study cannot be done if we have to obtain informed consent from every patient before we administer these medications.

Host: And so, Andy, at what stage is the study and what's the duration of it? Where is it at now, and how long does it go on for?

Andy Betz, RN, CNP: Yeah. We're not enrolling patients in this yet. We're still in the process of getting everything in place for approval of the study. And Dr. Zeeb, you can probably answer that question a little bit better, kind of where we think, or timing wise, when we think we might be ready to actually start enrolling patients. And, because there's two phases to this trial, Joey, there's potential that we could be ready to enroll some hospital-based patients before pre-hospital or vice versa. A lot of moving parts in a multicenter National Department of Defense-funded study like this.

Paul Zeeb, MD: That's true. I mean, EMS has to be trained. Our staff have to be trained at the hospital. So, there are a lot of moving parts. We are just starting the public notification process. We hope to be able to start enrolling patients in the fall. But time will tell. We just have to jump through all the hoops and get all, everything in place.

This process is governed by the Institutional Review Board at the home-sponsoring institution, which is University of Pittsburgh Medical Center in Pittsburgh. So, we have to satisfy all these rules. We have to give the public an opportunity to give comment.

Chance Spalding, MD: And Joey, to this particular podcast, what Dr. Zeeb was talking about is that we need to inform the public. This is a start of that. This is a version of that. We will be out talking like this a lot to the public, to the community, news, articles, podcasts, to go through. And not only let them know what the trial is about, but also allowing them to say I would be okay participating in this, or I don't want to. You are allowed to opt out of participating in a trial like this. Typically, we're a wristband to then go through and notify providers that this is not something I want to participate in. 

Paul Zeeb, MD: Yeah, we are making aggressive efforts. We even have brochures regarding the study and they're in languages other than English for those members of our population where English is not the native language. So, we have brochures in Spanish, Somali and Nepali that will also be distributed with information regarding the study.

Host: And I know it's early in the game here, Dr. Zeeb, but at what point might a study like this start to bear fruit, so to speak?

Paul Zeeb, MD: I think they're looking for about 1400 patients across the country. Then, they anticipate it's probably going to be three years of patient enrollment and experience in a year for analysis. So, we're probably looking at three and a half to four years before we've had any conclusions.

There is a monitoring process in place. So if there's something found to be a putting patients at risk as part of the study, the study can be terminated early. I doubt they'll find that there's superior efficacy that they'll terminate the study early because it's showing that calcium is the best thing since sliced bread. But there are steps in place for ongoing analysis.

Host: And in summary here, Dr. Spalding, how can patients and their families learn more about this CAVALIER study as well as other clinical trials going on like it?

Chance Spalding, MD: Yeah, there's the whole network of clinical trials that currently go on. You can always go to clinicaltrials.gov. I will warn you, it's an overwhelming number of trials that occur, and it's not just trauma, that's cancer that's everywhere. But specifically, if you're interested in learning more about LITES trials, CAVALIER type trials and trauma trials, there's a website, it's www.litesnetwork.org and you can slash CAVALIER and that will bring you directly to this trial. If you have any questions or you want more inquiry, you can also email us at mcri@mchs.com. Mount Carmel Research Institute @mchs.com and we'll go through and be able to provide any information that you need.

Host: Well, folks, we trust you are now more familiar with the CAVALIER study. Gentlemen, we look forward to hearing the results. And perhaps when they start to come through, we can have you on again to give us an update. Thanks so much again.

Chance Spalding, MD: Great. Thanks, Joey.

Paul Zeeb, MD: Thank you.

Andy Betz, RN, CNP: Thanks.

Host: for more information in general about the program, please do visit mountcarmelhealth.com/services/trauma-services.

Now, if you found this podcast helpful, please do share it on your social media. And thanks again for being part of Wellness in Reach, a Mount Carmel Podcast.