Established Status Epilepticus Treatment Trial (ESETT)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2015 by University of Virginia
Sponsor:
Collaborators:
University of Michigan
Medical University of South Carolina
Children's Research Institute
University of Minnesota - Clinical and Translational Science Institute
Information provided by (Responsible Party):
Jaideep Kapur, MD, University of Virginia
ClinicalTrials.gov Identifier:
NCT01960075
First received: October 8, 2013
Last updated: May 6, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Benzodiazipine Refractory Status Epilepticus
Drug: Fosphenytoin
Drug: Levetiracetam
Drug: Valproic acid
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Blinded, Comparative Effectiveness Study of Fosphenytoin, Valproic Acid, or Levetiracetam in the Emergency Department Treatment of Patients With Benzodiazepine-refractory Status Epilepticus.

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Clinical cessation of status epilepticus [ Time Frame: Within 60 minutes after the start of study drug infusion ] [ Designated as safety issue: No ]
    Determined by the absence of clinically apparent seizures and improving responsiveness without the use of additional anti-seizure medication


Secondary Outcome Measures:
  • Occurrence of life threatening hypotension or cardiac arrhythmia [ Time Frame: Within 60 minutes after the start of study drug infusion ] [ Designated as safety issue: Yes ]
  • Admission to ICU [ Time Frame: 7 days from enrollment ] [ Designated as safety issue: No ]
  • Time to termination of seizures [ Time Frame: Within 60 minutes after the start of study drug infusion ] [ Designated as safety issue: No ]
  • Intubation [ Time Frame: Within 60 minutes after the start of study drug infusion ] [ Designated as safety issue: Yes ]
  • Seizure recurrence [ Time Frame: Within 60 minutes after the start of study drug infusion ] [ Designated as safety issue: Yes ]
  • Mortality [ Time Frame: Within 30 days of randomization ] [ Designated as safety issue: Yes ]
  • Richmond agitation and sedation score [ Time Frame: Within 60 minutes after the start of study drug infusion ] [ Designated as safety issue: Yes ]
  • Length of stay in the ICU and hospital [ Time Frame: Within 30 days of randomization ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Effectiveness in children [ Time Frame: Within 60 minutes after the start of study drug infusion ] [ Designated as safety issue: Yes ]
    Final objective is to determine the effectiveness, rate of adverse reactions of these drugs in children with established status epilepticus.


Estimated Enrollment: 795
Study Start Date: August 2015
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fosphenytoin (FOS)
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.
Drug: Fosphenytoin
Active Comparator: Valproic acid
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.
Drug: Valproic acid
Active Comparator: Levetiracetam
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.
Drug: Levetiracetam

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.; ontinued 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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01960075

Contacts
Contact: Jaideep Kapur, MBBS, PhD 434-924-5312 jk8t@virginia.edu
Contact: Amy Fansler, MPH 434-982-6027 acf7h@virginia.edu

Locations
United States, Virginia
University of Virginia Not yet recruiting
Charlottesville, Virginia, United States, 22908
Contact: Jaideep Kapur, MBBS, PhD    434-924-5312    jk8t@virginia.edu   
Contact: Amy Fansler, MPH    434-982-6027    acf7h@virginia.edu   
Principal Investigator: Jaideep Kapur, MBBS, PhD         
Sponsors and Collaborators
University of Virginia
University of Michigan
Medical University of South Carolina
Children's Research Institute
University of Minnesota - Clinical and Translational Science Institute
Investigators
Study Chair: Jaideep Kapur, MBBS, PhD University of Virginia
Principal Investigator: Robert Silbergleit, MD University of Michigan
Principal Investigator: James Chamberlain, MD Children's National Health System
Principal Investigator: Jordan Elm, PhD Medical University of South Carolina
  More Information

Additional Information:
No publications provided

Responsible Party: Jaideep Kapur, MD, Professor of Neurology and Neuroscience, University of Virginia
ClinicalTrials.gov Identifier: NCT01960075     History of Changes
Other Study ID Numbers: 18078, 119756
Study First Received: October 8, 2013
Last Updated: May 6, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Virginia:
status epilepticus, refractory, benzodiazepine, fosphenytoin, levetiracetam, valproic acid

Additional relevant MeSH terms:
Status Epilepticus
Brain Diseases
Central Nervous System Diseases
Epilepsy
Nervous System Diseases
Etiracetam
Fosphenytoin
Phenytoin
Piracetam
Valproic Acid
Anticonvulsants
Antimanic Agents
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
GABA Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Neurotransmitter Agents
Nootropic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Psychotropic Drugs
Sodium Channel Blockers
Therapeutic Uses
Tranquilizing Agents
Voltage-Gated Sodium Channel Blockers

ClinicalTrials.gov processed this record on May 29, 2015