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Trial record 1 of 1 for:    ESETT
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Established Status Epilepticus Treatment Trial (ESETT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01960075
Recruitment Status : Completed
First Posted : October 10, 2013
Results First Posted : February 28, 2020
Last Update Posted : June 14, 2021
Sponsor:
Collaborators:
University of Michigan
Medical University of South Carolina
Children's National Research Institute
University of Minnesota
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Jaideep Kapur, MD, University of Virginia

Study Description
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Brief Summary:

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 or disease Intervention/treatment Phase
Benzodiazepine Refractory Status Epilepticus Drug: Fosphenytoin Drug: Levetiracetam Drug: Valproic acid Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 478 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: ESETT had 478 enrollments. They were 16 re-enrollers. This was an EFIC trial so all consents happened after treatment and all enrollments went through the same process of consent even if they were re-enrolled. Some information presented here only includes the first 400 patients since there was a prespecified stopping rule and the trial stopped early for futility.
Masking: Triple (Participant, 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.
Study Start Date : October 2015
Actual Primary Completion Date : February 2019
Actual Study Completion Date : May 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants With Clinical Cessation of Status Epilepticus - Intention to Treat [ Time Frame: Within 60 minutes after the start of study drug infusion ]
    Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Intention to treat

  2. Number of Participants With Clinical Cessation of Status Epilepticus - Per-protocol Analysis [ Time Frame: Within 60 minutes after the start of study drug infusion ]
    Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Per-protocol analysis

  3. Number of Participants With Clinical Cessation of Status Epilepticus - Adjudicated Outcomes Analysis [ Time Frame: Within 60 minutes after the start of study drug infusion ]
    Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. The Adjudicated outcomes analysis is different from Outcome measure 1 because a central clinical phenomenology core of four neurologists adjudicated from the medical records the time to seizure cessation, the time in status epilepticus before trial-drug initiation, and the cause of the seizure. For each enrollment, two neurologists from this core group conducted independent initial reviews and then determined a consensus or consulted a third adjudicator, as needed. Adjudicators were unaware of the treatment assignments and made determinations by medical record review.


Secondary Outcome Measures :
  1. Number of Participants With Admission to Intensive Care Unit [ Time Frame: Admission to intensive care unit after start of study drug infusion, where the ICU is the initial inpatient unit for the patient ]
    ICU admission is recorded as occurring only if the ICU is the initial inpatient unit for the patient.

  2. Length of ICU Stay [ Time Frame: number of calendar days after the day of ED arrival until hospital discharge or subject end-of-study ]
    Length of stay is determined by the number of calendar days after the day of ED arrival until hospital discharge or subject end-of-study.

  3. Minutes From Start of Trial Drug Infusion to Termination of Seizures for Patients With Treatment Success [ Time Frame: start of drug infusion to seizure cessation ]
    The time to termination of seizures is the interval from the start of study drug infusion to cessation of clinically apparent seizure in those who meet the primary outcome.

  4. Number of Participants With Seizure Cessation Within 20 Minutes for Patients With Treatment Success [ Time Frame: within 20 minutes ]
    Number of participants with seizure cessation within 20 minutes of study drug initiation for patients with treatment success. This outcome measure was only reported in the Supplementary materials to the Primary Paper.

  5. Length of Hospital Stay [ Time Frame: length of hospital stay ]
    Length of hospital stay in days


Other Outcome Measures:
  1. Number of Participants With Safety Outcome: Life Threatening Hypotension [ Time Frame: within 60 minutes of the start of study drug infusion ]
    Life-threatening hypotension within 60 minutes of the start of study drug infusion

  2. Number of Participants With Safety Outcome: Life-threatening Cardiac Arrhythmia [ Time Frame: within 60 minutes of the start of study drug infusion ]
    Life-threatening cardiac arrhythmia within 60 minutes of the start of study drug infusion

  3. Number of Participants With Safety Outcome: Endotracheal Intubation [ Time Frame: within 60 minutes of start of study drug infusion ]
    Endotracheal intubation within 60 minutes of start of study drug infusion

  4. Number of Participants With Safety Outcome: Acute Anaphylaxis [ Time Frame: within 6 hours of the start of study drug infusions ]
    Acute anaphylaxis is defined as a clinical presentation consistent with life threatening allergic reaction occurring within 6 hours of the start of study drug infusions and manifested as urticaria in combination with either (1) a systolic blood pressure of < 90 mmHg sustained for greater than 5 minutes, or (2) objective evidence of airway obstruction, and for which the patient was treated with antihistamines and/or steroids.

  5. Number of Participants With Safety Outcome: Acute Respiratory Depression [ Time Frame: 24 hours ]
    Respiratory depression is defined as impairment of ventilation or oxygenation necessitating definitive endotracheal intubation and mechanical ventilation. It is distinct from intubations performed only for airway protection in those with decreased levels of consciousness. It does not include those getting only supraglottic airways or transient bag-valve-mask support.

  6. Number of Participants With Safety Outcome: Hepatic Transaminase or Ammonia Elevations [ Time Frame: 24 hours ]
    Safety outcome: Hepatic transaminase or ammonia elevations

  7. Number of Participants With Safety Outcome: Purple Glove Syndrome [ Time Frame: 24 hours ]
    Purple glove syndrome is defined as the presence of all three of the findings of the objective edema: discoloration, and pain in the distal extremity in which study drug was administered, with or without known extravasation, and for which there is no other evident etiology.

  8. Number of Participants With Safety Outcome: Death [ Time Frame: 30 days ]
    Safety outcome: Death

  9. Number of Participants With Safety Outcome: Acute Seizure Recurrence [ Time Frame: 60 minutes to 12 hours after start of study drug infusion ]
    acute seizure recurrence 60 minutes to 12 hours after start of study drug infusion


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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.; 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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01960075


Locations
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Sponsors and Collaborators
University of Virginia
University of Michigan
Medical University of South Carolina
Children's National Research Institute
University of Minnesota
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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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
  Study Documents (Full-Text)

Documents provided by Jaideep Kapur, MD, University of Virginia:
Study Protocol and Statistical Analysis Plan  [PDF] December 5, 2016
Informed Consent Form  [PDF] January 5, 2015

More Information
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Additional Information:

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Jaideep Kapur, MD, Professor of Neurology and Neuroscience, University of Virginia
ClinicalTrials.gov Identifier: NCT01960075    
Other Study ID Numbers: 18078
119756 ( Other Identifier: ClinicalTrials.gov )
U01NS088034 ( U.S. NIH Grant/Contract )
First Posted: October 10, 2013    Key Record Dates
Results First Posted: February 28, 2020
Last Update Posted: June 14, 2021
Last Verified: May 2021
Keywords provided by Jaideep Kapur, MD, University of Virginia:
status epilepticus, refractory, benzodiazepine, fosphenytoin, levetiracetam, valproic acid
Additional relevant MeSH terms:
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Status Epilepticus
Seizures
Neurologic Manifestations
Nervous System Diseases
Fosphenytoin
Levetiracetam
Valproic Acid
Anticonvulsants
Nootropic Agents
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
Sodium Channel Blockers
Membrane Transport Modulators