Established Status Epilepticus Treatment Trial (ESETT)

University of Virginia

Status and phase: Completed; Phase 3

Conditions: Benzodiazepine Refractory Status Epilepticus

Treatments: Drug: Levetiracetam; Drug: Valproic acid; Drug: Fosphenytoin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01960075

18078

U01NS088034 (U.S. NIH Grant/Contract)

119756 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 478 patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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478 participants in 3 patient groups

Fosphenytoin (FOS)

Active Comparator group

Description:

Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes.

Treatment:

Drug: Fosphenytoin

Valproic acid

Active Comparator group

Description:

Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes.

Treatment:

Drug: Valproic acid

Levetiracetam

Active Comparator group

Description:

Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes.

Treatment:

Drug: Levetiracetam