Lessons from the Established Status Epilepticus Treatment Trial

Epilepsy Behav. 2019 Dec;101(Pt B):106296. doi: 10.1016/j.yebeh.2019.04.049. Epub 2019 Oct 22.


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".

Keywords: Clinical trial; Levetiracetam; Methodology; Phenytoin; Status epilepticus; Valproate.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adult
  • Anticonvulsants / therapeutic use*
  • Benzodiazepines / therapeutic use
  • Child, Preschool
  • Clinical Trials as Topic / methods*
  • Clinical Trials as Topic / standards*
  • Diagnostic Tests, Routine / methods
  • Diagnostic Tests, Routine / standards
  • Double-Blind Method
  • Emergency Service, Hospital / standards*
  • Female
  • Humans
  • Levetiracetam / therapeutic use
  • Male
  • Status Epilepticus / diagnosis
  • Status Epilepticus / drug therapy*
  • Treatment Outcome
  • Valproic Acid / therapeutic use


  • Anticonvulsants
  • Benzodiazepines
  • Levetiracetam
  • Valproic Acid