
Jaideep Kapur, MBBS, PhD
The University of Virginia has received funding from the National Institute for Neurological Disorders and Stroke (NINDS) to oversee a 60-site, five-year clinical trial to test the safety and efficacy of ketamine as an add-on treatment for prolonged, generalized seizures. The first year of the study received $9.3 million in funding; the overall project will bring in nearly $30 million over five years.
Grand mal (the great malady) seizures, or generalized tonic-clonic seizures, consist of dramatic whole-body contractions alternating with stiffness. Fortunately, most of these seizures end within five minutes by themselves, but in some instances, they continue for hours or even days. These prolonged seizures (status epilepticus) threaten life by interfering with breathing and can cause permanent brain damage. Status epilepticus can occur in babies, young children, adults, or older adults. Many sufferers have epilepsy, but for others, this is the first seizure of their life. This may occur in the context of high fever, infection, stroke, or other brain insults. Some chemical war agents cause status epilepticus, which then results in brain damage, hence the name “nerve gas.”
In order to save lives and protect the brain, it is imperative to stop the seizures. The researchers first use drugs called benzodiazepines to terminate seizures; unfortunately, 30-40% of patients do not respond to benzodiazepines, and a second drug is used. A previous study conducted by UVA, Established Status Epilepticus Treatment Trial, demonstrated that commonly used anti-seizure medications are effective in about half the patients. It is desired to achieve a success rate better than 50%.
The Ketamine add-on therapy for Established Status Epilepticus Treatment Trial (KESETT) is a phase III randomized, double-blind clinical trial to test whether ketamine (1 or 3 mg/Kg) added to standard therapy, levetiracetam (60mg/Kg), is more effective than levetiracetam alone in treating status epilepticus after benzodiazepines have failed. There is considerable evidence that ketamine, a commonly used sedative and anti-convulsant, can arrest seizures and provide neuroprotective benefits. The trial will recruit children who are one year old or older, adults, and older adults since the condition affects people of all ages.
Through support from the NINDS (UG3NS131532), KESETT will be conducted by 60 academic medical centers and associated hospitals across the United States. These centers belong to two networks. The Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) is a clinical trials network funded by the NINDS, the National Heart Lung and Blood Institute (NHLBI), and the National Center for Advancing Translational Science (NCATS). The Pediatric Emergency Care Applied Research Network (PECARN), the first federally-funded multi-institutional network for research in pediatric emergency medicine in the United States, will enroll children with this condition.
Under the leadership of Jaideep Kapur, MBBS, PhD, the University of Virginia Brain Institute and School of Medicine-based team will coordinate this large-scale effort involving the production and testing of study drugs, regulatory approval by the Food and Drug Administration, the conduct of exception from informed consent activities, and clinical site initiation within the first year of the trial. The UVA team will work with other groups from the University of Michigan, Medical University of South Carolina, Children’s National Medical Center-George Washington University, Massachusetts General Hospital-Harvard University, and University of Minnesota to conduct the trial.
Read more in the UVA Health newsroom.