Established status epilepticus treatment trial (ESETT)

Phenytoin (PHT) has been the standard treatment for convulsive status epilepticus (SE) where initial benzodiazepines have failed for many years, despite that it has many limitations in the emergency situation. Valproate (VPA) and levetiracetam (LEV) are emerging as potentially superior alternatives, and there is an urgent need for an adequately powered comparative randomized controlled trial (RCT). An international group, having not succeeded in obtaining funding from the United Kingdom in 2010, is now preparing a revised proposal for submission to the National Institute of Neurological Disorders and Stroke (NINDS) to undertake a blinded comparative RCT using an adaptive design. This will be necessarily international and multicenter, requiring up to 1,500 patients from over 50 centers, and if successful will commence recruiting in 2012. The primary outcome, agreed from the 2009 SE workshop as pragmatic, generalizable, and clinically meaningful, will be cessation of seizures without need for other drug or sedation, and without serious adverse events, maintained for at least 2 h.