UVA will be part of a unique national trial examining the best medication for treating epileptic seizures.
Learn more about the trial, and how it differs from most clinical trials from Dr. J. Stephen Huff, a UVA specialist in epilepsy.
Clinical Trial Examines Epilepsy Medications
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J. Stephen Huff, MD
Dr. Huff was born in Carbondale, Illinois and grew up in Midwest Illinois and Indiana. He attended Butler University for his undergraduate degree. In 1979, he graduated Indiana University School of Medicine. Dr. Huff completed a flexible internship at Methodist Hospital of Indiana and a neurology residency and emergency medicine residency at the University of Cincinnati. He started at UVA in 1995. Outside of work, Dr. Huff's special interests include jazz and improvisational music. He contributes to UVA’s community radio station (WTJU 91.1) on Monday evenings.Learn more about Dr. Huff
Learn more about UVA Neurosciences
Transcription:
Clinical Trial Examines Epilepsy Medications
Melanie Cole (Host): UVA will be part of a unique national trial examining the best medication for treating epileptic seizures. My guest today is Dr. J. Steven Huff. He's board certified in neurology and emergency medicine at UVA Health System. Welcome to the show, Dr. Huff. Tell us a little bit about this ESETT trial. What is it and what is it seeking to determine?
Dr. J. Steven Huff (Guest): Sure. ESETT stands for Established Status Epilepticus Treatment Trial. It's a nationally-run study. Jaideep Kapur of neurology here at UVA is the overall coordinating investigator. I'm the site investigator here at the University of Virginia. Lea Becker is the clinical research coordinator. This is being employed and looked at at more than 20 sites across the US. Our goal, as always, is to do excellent, ethical research, compliant with regulations. The basic research question is we don't know what drugs work best for prolonged seizures. We know what class of medications are the diazepines--medications like Valium and others--are good first-line drugs, but if the patient doesn't respond, that is if a seizure continues, we don't know the best second-line drug to be used. So, this is a randomized perspective trial of three drugs that are known to be effective for seizures. There are no experimental agents in this study. The goal is to get enough patients, enough sites together, and enough data so that perhaps physicians will have the good idea to know which drug works best for prolonged benzo-diazapine refractory seizures.
Melanie: So, what's considered a prolonged seizure?
Dr. Huff: Generally, for status epilepticus, the definition has changed to the recent years. It's one seizure lasting longer than five minutes. One generalized seizure lasting more than five minutes, a convulsion, or several convulsions without the patient gaining full responsiveness in between.
Melanie: So, typically, these patients have been treated with benzo-diazapine, like Valium, as you said, and it's not fulfilling what it needs to do at that point?
Dr. Huff: That's correct. So, typically, rescue squad is summoned. EMS may give medicine like valium or Midazolam or another medication and often that stops the seizures. Then the question is, as I said, if the seizures continue, we physicians just don't know which drug is best after that.
Melanie: So, how is this trial different than normal clinical trials we discuss?
Dr. Huff: A couple of ways, basically. This has been a question--study question--that has been present for many years. A cornerstone of clinical research is informed consent. By the nature of this emergency, patients are unable to give informed consent, so we're employing something called EFIC—“Exception From Informed Consent”. This is an FDA-approved research technique. it complies with human research regulations and allows research to be conducted without consent if the life is at risk; if the best treatment is not known and the study might help; and if it's not possible to get instantaneous or contemporaneous permission. When the patient recovers, or when family or a legally authorized representative arrives, then a normal consent process will take place.
Melanie: Is emergency department care of this established status epilepticus the same everywhere, typically? Do you all kind of follow the same course of action?
Dr. Huff: It isn't. We know that a second-line drug needs to be given, whether that's Fosphenytoin, whether that's Levetiracetam, or Keppra, or whether that's valproic acid is just not known. There are many causes of seizures. Many times the cause of a seizure, even after extensive investigation isn't discovered, but of these three drugs, they're commonly known, but it hasn't been possible to get any high-level of evidence to give an idea which one is preferred. So, it's been a question that's been present for several years.
Melanie: So, if the study is looking at different medications to stop these seizures, what are you intending for these medications to do? Are there a few different ones you're going to try and are they going to be able to stop the seizure, hopefully, right away? What's the intention?
Dr. Huff: So, the idea is to halt the ongoing seizure activity. So, again, there are three drugs that will be studies: Fosphenytoin, Valproic, and Levetiracetam. These are all FDA-approved treatments for seizures and these drugs are prepared in an investigational pharmacy so that the physicians, the other caregivers providing the care won't know which drug is being given. Randomization for this study for the drug takes place before the patient arrival. So, the person arriving will get one of the study drugs and it won't be known until one hour. At one hour, unblinding is possible. Outcomes for this study are at 20 minutes and at one hour. Are seizures continuing? Is the patient improving with their level of consciousness? So, it should provide a high level of evidence because of what's called a “blinded study”. The treating providers don't know which drugs are being given. That's desirable in research because it's thought to avoid bias. Again, these are all drugs that are approved for seizure treatment.
Melanie: So, each of you doctors are going to like, flip a coin. You're going to just be taking one of these three medications and since there's not the exception from informed consent, what if there's an allergic reaction or any of those kinds of things going on?
Dr. Huff: Well, certainly, if there's an allergic reaction or an adverse reaction, the infusion would be stopped. It would be very unusual for any of these drugs to have an allergic reaction. There is a method for adverse event reporting which is pretty standard with literature. It's not really flipping a coin. I mean, it's more sophisticated than that in that through a central statistical service, the next drug up is determined. It's given to the different study sites. The physicians at the point of care do not know which one of these three drugs will be given, but it's not like I have a choice between one or three. It's the next drug up--the next investigational packet up will be given. At the moment of treatment, the physicians will not know which drug. But, like I say, this is desirable in research to try to avoid bias.
Melanie: That's fascinating. How common are these type of seizures or epileptic seizures, in general?
Dr. Huff: Well, epileptic seizures are pretty common. It's thought that somewhere around 1% of emergency department visits are seizure related. Continuing seizures, continuing generalized status epilepticus, is less common and even less common are seizures that don't respond to benzodiazepines. When given early, benzodiazepines are very effective drugs. So, this is of 20 sites. We're hoping the study's going to accumulate over 500 patients over a couple of years and that number is thought to be necessary in order for good evidence, in order for good statistical interpretation.
Melanie: Is this something that happens to both adults and pediatric patients?
Dr. Huff: It does happen to adults and children and many children’s' hospitals are participating in that. We've opted, just for simple logistical reasons, not to use it in patients less than 18 years old here at UVA at this time.
Melanie: So then, in just the last few minutes, just kind of summarize it for us and tell patients and listeners--this is an emergent situation, so how can they get more information about the trial, as well?
Dr. Huff: More information about the trial and, in fact, the entire study protocol is posted up at a website that's ESETT.org or you can send an email to seizure@virginia.edu and we'll be happy to provide more information individually. Again, a lot of information about the study is at the ESETT website.
Melanie: And would you give that website one more time?
Dr. Huff: Sure. That's www.esett.org.
Melanie: Thank you so much, Dr. Huff. That is fascinating information, really, and we wish you all the best and applaud all the great work that you're doing. Thanks for being with us today. You're listening to UVA Health Systems Radio. For more information, you can go to uvahealth.com. That's uvahealth.com. This is Melanie Cole, thanks so much for listening.
Clinical Trial Examines Epilepsy Medications
Melanie Cole (Host): UVA will be part of a unique national trial examining the best medication for treating epileptic seizures. My guest today is Dr. J. Steven Huff. He's board certified in neurology and emergency medicine at UVA Health System. Welcome to the show, Dr. Huff. Tell us a little bit about this ESETT trial. What is it and what is it seeking to determine?
Dr. J. Steven Huff (Guest): Sure. ESETT stands for Established Status Epilepticus Treatment Trial. It's a nationally-run study. Jaideep Kapur of neurology here at UVA is the overall coordinating investigator. I'm the site investigator here at the University of Virginia. Lea Becker is the clinical research coordinator. This is being employed and looked at at more than 20 sites across the US. Our goal, as always, is to do excellent, ethical research, compliant with regulations. The basic research question is we don't know what drugs work best for prolonged seizures. We know what class of medications are the diazepines--medications like Valium and others--are good first-line drugs, but if the patient doesn't respond, that is if a seizure continues, we don't know the best second-line drug to be used. So, this is a randomized perspective trial of three drugs that are known to be effective for seizures. There are no experimental agents in this study. The goal is to get enough patients, enough sites together, and enough data so that perhaps physicians will have the good idea to know which drug works best for prolonged benzo-diazapine refractory seizures.
Melanie: So, what's considered a prolonged seizure?
Dr. Huff: Generally, for status epilepticus, the definition has changed to the recent years. It's one seizure lasting longer than five minutes. One generalized seizure lasting more than five minutes, a convulsion, or several convulsions without the patient gaining full responsiveness in between.
Melanie: So, typically, these patients have been treated with benzo-diazapine, like Valium, as you said, and it's not fulfilling what it needs to do at that point?
Dr. Huff: That's correct. So, typically, rescue squad is summoned. EMS may give medicine like valium or Midazolam or another medication and often that stops the seizures. Then the question is, as I said, if the seizures continue, we physicians just don't know which drug is best after that.
Melanie: So, how is this trial different than normal clinical trials we discuss?
Dr. Huff: A couple of ways, basically. This has been a question--study question--that has been present for many years. A cornerstone of clinical research is informed consent. By the nature of this emergency, patients are unable to give informed consent, so we're employing something called EFIC—“Exception From Informed Consent”. This is an FDA-approved research technique. it complies with human research regulations and allows research to be conducted without consent if the life is at risk; if the best treatment is not known and the study might help; and if it's not possible to get instantaneous or contemporaneous permission. When the patient recovers, or when family or a legally authorized representative arrives, then a normal consent process will take place.
Melanie: Is emergency department care of this established status epilepticus the same everywhere, typically? Do you all kind of follow the same course of action?
Dr. Huff: It isn't. We know that a second-line drug needs to be given, whether that's Fosphenytoin, whether that's Levetiracetam, or Keppra, or whether that's valproic acid is just not known. There are many causes of seizures. Many times the cause of a seizure, even after extensive investigation isn't discovered, but of these three drugs, they're commonly known, but it hasn't been possible to get any high-level of evidence to give an idea which one is preferred. So, it's been a question that's been present for several years.
Melanie: So, if the study is looking at different medications to stop these seizures, what are you intending for these medications to do? Are there a few different ones you're going to try and are they going to be able to stop the seizure, hopefully, right away? What's the intention?
Dr. Huff: So, the idea is to halt the ongoing seizure activity. So, again, there are three drugs that will be studies: Fosphenytoin, Valproic, and Levetiracetam. These are all FDA-approved treatments for seizures and these drugs are prepared in an investigational pharmacy so that the physicians, the other caregivers providing the care won't know which drug is being given. Randomization for this study for the drug takes place before the patient arrival. So, the person arriving will get one of the study drugs and it won't be known until one hour. At one hour, unblinding is possible. Outcomes for this study are at 20 minutes and at one hour. Are seizures continuing? Is the patient improving with their level of consciousness? So, it should provide a high level of evidence because of what's called a “blinded study”. The treating providers don't know which drugs are being given. That's desirable in research because it's thought to avoid bias. Again, these are all drugs that are approved for seizure treatment.
Melanie: So, each of you doctors are going to like, flip a coin. You're going to just be taking one of these three medications and since there's not the exception from informed consent, what if there's an allergic reaction or any of those kinds of things going on?
Dr. Huff: Well, certainly, if there's an allergic reaction or an adverse reaction, the infusion would be stopped. It would be very unusual for any of these drugs to have an allergic reaction. There is a method for adverse event reporting which is pretty standard with literature. It's not really flipping a coin. I mean, it's more sophisticated than that in that through a central statistical service, the next drug up is determined. It's given to the different study sites. The physicians at the point of care do not know which one of these three drugs will be given, but it's not like I have a choice between one or three. It's the next drug up--the next investigational packet up will be given. At the moment of treatment, the physicians will not know which drug. But, like I say, this is desirable in research to try to avoid bias.
Melanie: That's fascinating. How common are these type of seizures or epileptic seizures, in general?
Dr. Huff: Well, epileptic seizures are pretty common. It's thought that somewhere around 1% of emergency department visits are seizure related. Continuing seizures, continuing generalized status epilepticus, is less common and even less common are seizures that don't respond to benzodiazepines. When given early, benzodiazepines are very effective drugs. So, this is of 20 sites. We're hoping the study's going to accumulate over 500 patients over a couple of years and that number is thought to be necessary in order for good evidence, in order for good statistical interpretation.
Melanie: Is this something that happens to both adults and pediatric patients?
Dr. Huff: It does happen to adults and children and many children’s' hospitals are participating in that. We've opted, just for simple logistical reasons, not to use it in patients less than 18 years old here at UVA at this time.
Melanie: So then, in just the last few minutes, just kind of summarize it for us and tell patients and listeners--this is an emergent situation, so how can they get more information about the trial, as well?
Dr. Huff: More information about the trial and, in fact, the entire study protocol is posted up at a website that's ESETT.org or you can send an email to seizure@virginia.edu and we'll be happy to provide more information individually. Again, a lot of information about the study is at the ESETT website.
Melanie: And would you give that website one more time?
Dr. Huff: Sure. That's www.esett.org.
Melanie: Thank you so much, Dr. Huff. That is fascinating information, really, and we wish you all the best and applaud all the great work that you're doing. Thanks for being with us today. You're listening to UVA Health Systems Radio. For more information, you can go to uvahealth.com. That's uvahealth.com. This is Melanie Cole, thanks so much for listening.