University of Virginia Brain Institute and School of Medicine researchers have received an initial $9.3 million award from the National Institutes of Health for a $30 million clinical trial to determine if the powerful anesthetic ketamine can save patients from prolonged, life-threatening grand mal seizures that won't respond to other treatments.
"Status epilepticus," as the seizures are known, are seizures that last more than five minutes or that strike repeatedly without the person regaining consciousness between seizures. These ceaseless seizures are considered a medical emergency and can require intubation and lead to permanent brain damage or even death.
The seizures are typically treated with anticonvulsants called benzodiazepines. However, many patients – both adults and children – don't respond to those drugs.
UVA's new trial, called the Ketamine add-on therapy for the Established Status Epilepticus Treatment Trial, or KESETT, will evaluate whether adding ketamine to the standard treatment helps improve outcomes for patients suffering status epilepticus.
We wish to determine whether adding ketamine to existing treatment would terminate status epilepticus in more patients than the current treatment. Our hope is that this trial can improve treatment guidelines for patients suffering from these dangerous seizures."
Jaideep Kapur, MD, PhD, neurologist, co-director of UVA's Brain Institute and epileptologist (epilepsy expert), UVA Health and the School of Medicine
Stopping status epilepticus
UVA's new trial builds on its previous Established Status Epilepticus
Treatment Trial (ESETT), which provided the first definitive answers about how and when three drugs commonly used to treat status epilepticus should be used. Prior to the trial, doctors had little understanding of the drugs' effectiveness or when each should be deployed. In the end, the researchers determined that the drugs – levetiracetam, fosphenytoin and valproate – were all about equally effective but that they stopped status epilepticus in only about 47% of adult trial participants and 52% of children.
The Brain Institute's massive new trial seeks to improve those outcomes. The randomized, double-blinded trial will evaluate whether adding 1 mg or 3 mg of ketamine can stop the prolonged seizures in more patients than the existing treatments alone.
In particular, the trial will look at outcomes in children 1 year and older. The researchers expect children ages 1-17 will make up approximately a third of the hundreds of participants they plan to enroll in the trial.
The potential of ketamine
The researchers believe ketamine could be beneficial based on recent human studies, extensive drug modeling and other factors, including safety data. While the drug has recently received much attention in the news, emergency physicians have used it safely and effectively as a sedative for decades. It is also a known anti-convulsant.
The trial is expected to take place at approximately 60 sites over the next several years.
"Each year, as many as 160,000 Americans suffer from status epilepticus, and this trial promises to bring new and improved treatment for them," Kapur said. "The University of Virginia team is grateful for the opportunity to partner with our colleagues at other leading institutions to perform this groundbreaking work."
Funding for the trial is provided by the NIH's National Institute of Neurological Disorders and Stroke, grant No. UG3NS131532.
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