The University of Virginia Brain Institute and School of Medicine are spearheading a groundbreaking $30 million clinical trial to investigate whether ketamine could provide a breakthrough treatment for patients suffering from status epilepticus, a severe form of seizures that can lead to permanent brain damage or death if left untreated.
The research team has received an initial $9.3 million award from the National Institutes of Health's National Institute of Neurological Disorders and Stroke to launch the Ketamine add-on therapy for the Established Status Epilepticus Treatment Trial (KESETT).
Understanding Status Epilepticus
Status epilepticus is characterized by seizures lasting more than five minutes or recurring seizures without consciousness recovery between episodes. This condition affects up to 160,000 Americans annually and represents a critical medical emergency often requiring intensive intervention, including intubation.
While benzodiazepines are the current standard first-line treatment, many patients show resistance to these anticonvulsants. Previous research through the Established Status Epilepticus Treatment Trial (ESETT) revealed that commonly used second-line drugs - levetiracetam, fosphenytoin, and valproate - demonstrate limited efficacy, with success rates of only 47% in adults and 52% in children.
The KESETT Trial Design
"We wish to determine whether adding ketamine to existing treatment would terminate status epilepticus in more patients than the current treatment," explains Dr. Jaideep Kapur, neurologist and co-director of UVA's Brain Institute. "Our hope is that this trial can improve treatment guidelines for patients suffering from these dangerous seizures."
The trial will employ a randomized, double-blinded design to evaluate two ketamine dosage levels - 1 mg and 3 mg - as add-on therapy to standard treatments. The study will span approximately 60 sites and place special emphasis on pediatric outcomes, with children ages 1-17 expected to comprise about one-third of the participant pool.
Scientific Rationale and Safety Considerations
The selection of ketamine for this trial is supported by recent human studies, comprehensive drug modeling, and established safety data. While ketamine has gained recent public attention for various applications, emergency physicians have successfully used it as a sedative for decades, and its anticonvulsant properties are well-documented.
The research team's approach builds upon UVA's previous ESETT study, which provided the first definitive guidance on the use of second-line anticonvulsant medications. This new investigation represents a potential paradigm shift in status epilepticus treatment, addressing a critical gap in current therapeutic options.
