Established Status Epilepticus Treatment Trial

Overview

About this study

The primary objective is to determine the most effective and/or the least effective treatment of benzodiazepine-refractory status epilepticus (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. The final objective is to ensure that the trial is informative for treatment of established SE in children by describing the effectiveness, safety, and rate of adverse reactions of these drugs in children.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location	Status
Rochester, Minn. Mayo Clinic principal investigator M. Fernanda Bellolio, M.D.	Closed for enrollment

Mayo Clinic Location

Status

Rochester, Minn.

Mayo Clinic principal investigator

M. Fernanda Bellolio, M.D.

Closed for enrollment

More information

Publications

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 for ESE. The ESE treatment trial is designed to determine the most effective and/or the least effective treatment of ESE among patients older than 2 years by comparing three arms: fosphenytoin (fPHT) levetiracetam (LVT), 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 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 >0.975 or the probability that a treatment is the least effective is >0.975 for any treatment. Proposed total sample size is 795, which provides 90% power to identify the most effective and/or the least effective treatment when one treatment arm has a true response rate of 65% and the true response rate is 50% in the other two arms. Read More on PubMed
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. Read More on PubMed

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