The Established Status Epilepticus Treatment Trial (ESETT) is a multicenter, randomized, double-blind, comparative effectiveness study of fos-phenytoin, levetiracetam, and valproic acid in subjects with benzodiazepine-refractory status epilepticus. Patients will be recruited by two national emergency research networks: Neurology Emergency Treatment Trials (NETT) network and Pediatric Emergency Care and Applied Research Network (PECARN). Each network has successfully undertaken a Status Epilepticus treatment trial under exception from informed consent (EFIC) rules.
Objectives: The primary objective is to determine the most effective and/or the least effective treatment of benzodiazepine-refractory SE among patients older than 2 years. There are three active treatment arms being compared: fosphenytoin (FOS), levetiracetam (LEV), and valproic acid (VPA). The second objective is comparison of three drugs with respect to secondary outcomes. Final objective is to ensure that the trial is informative for treatment of ESE in children by describing the effectiveness, rate of adverse reactions of these drugs in children.
Participating Sites: Patients will be recruited by two national emergency research networks: Neurology Emergency Treatment Trials network(NETT) and Pediatric Emergency Care and Applied Research Network (PECARN). Each network has successfully undertaken a SE treatment trial under EFIC rules.
Inclusion Criteria: Patient witnessed to seize for greater than 5 minute duration prior to treatment with study drug; Patient received adequate dose of benzodiazepines. The last dose of a benzo was administered in the 5-30 minutes prior to study drug administration. The doses may be divided.; continued or recurring seizure in the Emergency Department; Age 2 years or older
Exclusion Criteria: Known pregnancy; Prisoner; Opt-out identification; Treatment with a second line anticonvulsant (FOS, PHT, VPA, LEV, phenobarbital or other agents defined in the MoP) for this episode of SE; Treatment with sedatives with anticonvulsant properties other than benzodiazepines (propofol, etomidate, ketamine or other agents defined in the MoP); Endotracheal intubation; Acute traumatic brain injury; Known metabolic disorder; Known liver disease; Known severe renal impairment; Known allergy or other known contraindication to FOS, PHT, LEV, or VPA; Hypoglycemia < 50 mg/dL; Hyperglycemia > 400 mg/dL; Cardiac arrest and post-anoxic seizures