Benzodiazepine-refractory status epilepticus (Established Status Epilepticus, ESE) is a relatively common emergency condition with several widely used treatments. There are no controlled, randomized, blinded clinical trials to compare the efficacy and tolerability of currently available treatments of ESE. This and the accompanying Statistical and Data Management Center (SDMC) application describe the ESE treatment trial (ESETT), which is designed to determine the most effective and/or the least effective treatment of ESE among patients older than two years by comparing three arms: fosphenytoin (FOS), levetiracetam (LEV), and valproic acid (VPA). This is a multicenter, randomized, double-blind, Bayesian adaptive, Phase III comparative effectiveness trial. Up to 795 patients will be randomized initially 1:1:1 and response-adaptive randomization will occur after 300 patients have been recruited. Randomization will be stratified by three age groups, 2-18, 19-65, and 66 years and older. The primary outcome measure is cessation of clinical seizure activity and improving mental status, without serious adverse effects or further intervention at 60 min after administration of study drug. Each subject will be followed until discharge or 30 days from enrollment. This trial will include interim analyses for early success and futility. This trial will be considered a success if the probability that a treatment is the most effective is greater than 0.975 or the probability that a treatment is the least effective is greater than 0.975 for any treatment. This will be the first phase III clinical trial of ESE in children and adults.

Public Health Relevance

Status epilepticus (SE), consisting of prolonged seizures, is a neurological emergency that can result in brain injury or even death. Patients in SE are initially treated with benzodiazepines, but approximately 33% do not respond to these drugs;these patients are considered to have established SE (ESE). ESE treatment trial (ESETT) seeks to determine which drug, among Fosphenytoin, Levetiracetam and Valproic acid, is the most effective (or least effective) in terminating ESE.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01NS088034-01
Application #
8752365
Study Section
Special Emphasis Panel (ZNS1-SRB-G (74))
Program Officer
Janis, Scott
Project Start
2014-09-30
Project End
2019-08-31
Budget Start
2014-09-30
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$6,170,975
Indirect Cost
$696,255
Name
University of Virginia
Department
Neurology
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904