Convulsive status epilepticus (SE) is a relatively common emergency condition affecting individuals of all ages. The primary goal of treatment is prompt termination of seizures. Where first-line treatment with benzodiazepine has failed to achieve this, a condition known as established SE (ESE), there is uncertainty about which agent to use next. The Established Status Epilepticus Treatment Trial (ESETT) is a 3-arm (valproate (VPA), fosphenytoin (FOS), levetiracetam (LEV)), phase III, double-blind randomized comparative effectiveness study in patients aged 2 years and above with established convulsive SE. Enrollment was completed in January 2019, and the results are expected later this year. We discuss lessons learnt during the conduct of the study in relation to the following: ethical considerations; trial design and practical implementation in emergency settings, including pediatric and adult populations; quality assurance; and outcome determination where treating emergency clinicians may lack specialist expertise. We consider that the ESETT is already informing both clinical practice and future trial design. This article is part of the Special Issue “Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures"
Bibliographical noteFunding Information:
All authors were supported by the ESETT study grant from NIH/NINDS (U01NS088034). Dr. Chamberlain and the enrolling sites from the Pediatric Emergency Care Applied Research Network (PECARN) were supported by grants from the Health Resources and Services Administration (HRSA), Maternal and Child Health Bureau (MCHB), Emergency Medical Services for Children (EMSC) Network Development Demonstration Program under cooperative agreements U03MC00008, U03MC00001, U03MC00003, U03MC00006, U03MC00007, U03MC22684, and U03MC22685. Dr. Coles reports grants from NIH/NINDS, during the conduct of the study; personal fees from Neurelis Pharmaceuticals, grants from Sollievo, outside the submitted work; Dr. Shinnar reports grants from NINDS, during the conduct of the study; personal fees from UCB Pharma, personal fees from Eisai, personal fees from Insys, outside the submitted work; Prof. Cock reports grants from NINDS, during the conduct of the study; personal fees from Sage Pharmaceuticals Ltd., personal fees from Eisai Europe Ltd., personal fees from UCB Pharma Ltd., personal fees from UK Epilepsy Nurse Specialist Association, nonfinancial support from Special Products Ltd., nonfinancial support from International League Against Epilepsy, Epilepsy Certification (education) Task Force, nonfinancial support from European Academy of Neurology, personal fees from Bial and Eisai, outside the submitted work; Dr. Fountain reports grants from NINDS, during the conduct of the study; grants from SK Lifesciences, grants from Neurelis, grants from Takeda, grants from GW Pharma, grants from Biogen, grants from UCB, outside the submitted work. Dr. Cloyd reports a grant from National Institute of Neurological Disorders and Stroke during the conduct of the study; personal fees from Neurelis Pharmaceuticals, grants from Sollievo, outside the submitted work. In addition, Dr. Cloyd has a patent entitled “Intranasal Drug Delivery” which the University of Minnesota has licensed to Sollievo.
Funding: Research discussed in this publication was supported by National Institutes of Health, National Institute of Neurological Disorders and Stroke under Awards U01NS073476, U01NS088034, U01NS088023, U01NS056975, U01NS059041, and R01NS099653.
© 2019 Elsevier Inc.
- Clinical trial
- Status epilepticus