The KESETT study is being performed so that doctors can know the best medications to use in the emergency department to treat people with prolonged seizures. KESETT will compare the anti-seizure medication most commonly used in those with prolonged seizures, called levetiracetam (also known as Keppra), with a combination of levetiracetam and another anti-seizure medication, called ketamine.  

Levetiracetam is currently the most common medication given in usual care for patients with prolonged seizures in the emergency department. Ketamine is also sometimes used to stop seizures, but is used much less commonly for this purpose. Ketamine is commonly given as usual care to treat pain or to provide sedation. Although both medications are FDA approved, and both are routinely used in the emergency department, neither are approved by the FDA for treating prolonged seizures. In this study, therefore, both are considered investigational for treating prolonged seizures and this is the first known study comparing the two medications combined together for seizure treatment.  

People with prolonged seizures are included in this study. This condition is called status epilepticus. Status epilepticus is a life-threatening situation in which the brain is in a state of persistent seizure. The condition is usually defined as a seizure, or rapidly recurring seizures, lasting longer than five minutes without stopping or without the person waking up. This study includes only those who remain in status epilepticus in the emergency department even after receiving a full dose of a benzodiazepine medication (like diazepam, also called Valium). Seizures affect people of all ages, so adults and children down to one year of age are included in this study. Many who develop status epilepticus are people with epilepsy, but others may have never had a seizure before. 

Every person coming to the emergency department who is eligible will be included in the study. Everyone in this study gets one of three types of study medicine to try to stop their seizure. As the study goes on, if one study medication does not appear to be as effective as the others, it will be given less frequently. Neither the study participant nor their doctor will know which study medicine they received while in the emergency department. If the study medication is effective, it is expected to stop seizures within 10 to 15 minutes. If the seizure does not stop, doctors will give whatever additional medications are needed as part of usual care. A rapid EEG headband may be placed on the study participant’s head to detect if silent seizures are occuring. The EEG headband stays on for one to four hours. After the study medicine is given, blood samples may be taken to measure the amount of study drug in the blood. Medical information about the study participant and their condition will be collected from the medical record until hospital discharge.  

No. In order for us to be able to determine which study medication or combination of medications are better at stopping seizures, patients will be given one of three possible study medications. Everyone will be randomly assigned to receive a single intravenous administration of study medication as early as possible. Random means assigned by chance, like the flip of a coin. Initially 1 in 3 patients will get study medication including levetiracetam alone. Another 1 in 3 will get study medication including levetiracetam and 1 mg/kg of ketamine. Another 1 in 3 get study medication including levetiracetam and 3 mg/kg of ketamine. As the study goes on, if one study medication does not appear to be as effective as the others, it will be given less frequently.

Research is normally only conducted with the express permission of the patient or parent/legal guardian. However, it is not possible to obtain patients’ or parent’s consent to study treatments in life-threatening emergencies like status epilepticus. Yet, emergency research is needed to learn what treatments work best. KESETT is conducted under federal regulations that allow an exception from informed consent (EFIC) for emergency research. Once a participant wakes up, or a parent or representative is located, they will be told about the study enrollment and asked to give their permission to continue in the study. 

In 1996, the Food and Drug Administration (FDA) developed specific regulations to permit emergency research without consent, in special circumstances, and with additional safeguards. These regulations recognize that there are situations in which patients or family members cannot give informed consent – but that there is also a need to advance emergency care through research.  

Usual care with levetiracetam stops seizures about half of the time. Combining levetiracetam with ketamine may stop seizures more often, less often, or the same as levetiracetam alone. People in the study may benefit from receiving a more effective medicine, but this is not guaranteed.  Participants may not get any benefit from being in this research study.  What is learned in this study may also help us to provide more effective treatment for patients with seizures in the future. 

Prolonged seizures that do not stop on their own is a medical emergency. Most of the risks of this condition are similar in those participating in the study and those not participating. It is possible that we will learn that one of the treatments in the study is better than the others. If this is the case, people in one treatment group may not have as good an outcome as those in the other groups.  

The study medicines, levetiracetam and ketamine, work in different ways, and have different risks. The risks of the study medicines are the same whether they are given in the study or for treatment of seizures outside of this study. However, there could be unknown risks of combining the two medicines together, since this is the first time this has been done as part of a research study. 

Risks and possible side effects of any of the study medicines include drowsiness, dizziness, an allergic reaction, or pain, discomfort, or inflammation where the medicine is injected in the vein.  Ketamine can cause vivid dreams, and a person can be confused or agitated until it wears off.  Rare side effects may also include abnormal heart rhythms, high blood pressure, or vocal cord spasms. There may be other unknown risks as well. 

If a blood sample is drawn for the study, it can cause slight discomfort, bruising or infection at the site. The EEG headband used in the study can also cause minor skin irritation.  

There is also a risk of breach of confidentiality related to participation in the study. We will do our best to keep all the medical information we collect confidential. Precautions are taken to secure this information.  

The National Institute of Neurological Disorders and Stroke (NINDS), part of the United States National Institutes of Health. 

Yes. Those who do not want to be enrolled in the study can indicate this on a medical alert. This can be marked on one’s own medical alert ID or bracelet or we will provide a medical alert wristband indicating “KESETT study declined” for those people upon request.