A Study to Compare the Effectiveness of Three Drugs, Fosphenytoin, Levetiracetam and Valproic Acid in Terminating Prolonged Seizures (Status Epilepticus) That do Not Respond to Benzodiazepines. (ESETT)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified October 2013 by University of Virginia
Sponsor:
Information provided by (Responsible Party):
Jaideep Kapur, MD, University of Virginia
ClinicalTrials.gov Identifier:
NCT01960075
First received: October 8, 2013
Last updated: March 3, 2014
Last verified: October 2013
  Purpose

The primary objective of the trial is to determine the most effective and/or the least effective treatment of benzodiazepine-refractory status epilepticus ( established status epilepticus) among patients older than 2 years. There are three active treatment arms being compared: fosphenytoin (FOS), Levetiracetam (LEV) and Valproic acid (VPA). Secondary objective is to measure the impact of the three drugs on secondary outcomes: time to termination of clinical seizures, intubation or admission to ICU within 24 hrs. of enrollment, and mortality. Final objective is to determine the effectiveness, rate of adverse reactions of these drugs in children with established status epilepticus.

The primary hypothesis is that the most effective ( or least effective) treatment can be identified.


Condition Intervention Phase
Status Epilepticus ( Prolonged Seizures) Not Responding to Benzodiazepines
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: Established Status Epilepticus Treatment Trial

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Clinical cessation of SE without life threatening hypotension or cardiac arrhythmias. [ Time Frame: 60 minutes from enrollment ] [ Designated as safety issue: Yes ]
    The primary outcome is clinical cessation of status epilepticus, without recurrent seizures, life-threatening hypotension or cardiac arrhythmia, or use of additional anti-seizure medications within 60 minutes of the start of study drug infusion.


Secondary Outcome Measures:
  • Admission to ICU, intubation and mortality [ Time Frame: 7 days from enrollment ] [ Designated as safety issue: Yes ]
    Secondary objective is to measure the impact of the three drugs on secondary outcomes: time to termination of clinical seizures, intubation or admission to ICU within 24 hrs. of enrollment, mortality and clinical cessation of status epileptcis and adverse effects analyzed separately.


Other Outcome Measures:
  • Effectiveness in children [ Time Frame: 60 minutes ] [ 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: July 2014
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:

  • Any patient aged 2 or older who is witnessed to have clinically apparent recurrent or ongoing convulsive activity in the emergency department and has already received adequate dose of benzodiazepines in the past 5-30 minutes for a witnessed generalized tonic-clonic seizure. The seizure and its initial treatment may have occurred prior to arrival in the ED.

4.1.2 Adequate doses of benzodiazepines for this study are determined to be: diazepam 10 mg IV, lorazepam 4 mg IV or midazolam 10mg IV or IM for those above 40 Kg. For children between 10-40 Kg adequate doses are: diazepam 0.3 mg/kg IV, lorazepam 0.1 mg/kg IV and midazolam 0.3 mg/kg IV or IM. These drugs may have been administered in two or more divided doses. A benzodiazepine given at home(such as rectal diazepam, buccal midazolam) will be included in defining "adequate doses" but it is recommended that another round of benzodiazepine be administered to the patient to qualify for the study unless this administration is considered unsafe. Although these doses are considered minimum adequate dose based on common clinical practice, it is recommended that the best practice is to administer 20 mg of diazepam or 8 mg lorazepam or 20 mg of midazolam in adults.

Exclusion Criteria:

  • Table 2 Criterion Measure Rationale

    1) Known pregnancy based 2)Prisoner Look for prison guards 3) Treatment with propofol, etomidate, ketamine or another sedative with anticonvulsant properties (except benzodiazepines) after initial seizure 4) Intubation 5) Acute post traumatic seizures . 6) Known Metabolic disorder 7Liver Disease 8) Contraindication to phenytoin, leveitieracetam or valproic acid, Includes allergy to any study drug and sustained hypotension.

    9) Hypoglycemia < 50 mg/dL 10) Hyperglycemia > 400 mg/dL 11) 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 4349245312 jk8t@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   
Principal Investigator: Jaideep Kapur, MBBS, PHD         
Sponsors and Collaborators
University of Virginia
  More 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: 119756
Study First Received: October 8, 2013
Last Updated: March 3, 2014
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:
Seizures
Status Epilepticus
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Etiracetam
Fosphenytoin
Valproic Acid
Phenytoin
Piracetam
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Nootropic Agents
Neuroprotective Agents
Protective Agents
Voltage-Gated Sodium Channel Blockers

ClinicalTrials.gov processed this record on October 01, 2014