Established Status Epilepticus Treatment Trial
- Conditions
- Benzodiazepine Refractory Status Epilepticus
- Interventions
- Registration Number
- NCT01960075
- Lead Sponsor
- University of Virginia
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 478
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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Valproic acid 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. Fosphenytoin (FOS) Fosphenytoin 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. Levetiracetam 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.
- Primary Outcome Measures
Name Time Method Number of Participants With Clinical Cessation of Status Epilepticus - Intention to Treat 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
Number of Participants With Clinical Cessation of Status Epilepticus - Adjudicated Outcomes Analysis 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.
Number of Participants With Clinical Cessation of Status Epilepticus - Per-protocol Analysis 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
- Secondary Outcome Measures
Name Time Method Number of Participants With Admission to Intensive Care Unit 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.
Length of ICU Stay 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.
Minutes From Start of Trial Drug Infusion to Termination of Seizures for Patients With Treatment Success 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.
Number of Participants With Seizure Cessation Within 20 Minutes for Patients With Treatment Success 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.
Length of Hospital Stay length of hospital stay Length of hospital stay in days
Trial Locations
- Locations (65)
Children's Medical Center UTSW
🇺🇸Dallas, Texas, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
UPMC Mercy Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Children's Hospital of Pittsburgh UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Memorial Hermann Texas medical Center
🇺🇸Houston, Texas, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
UCSF Benioff Children's Hospital
🇺🇸San Francisco, California, United States
San Francisco General Hospital
🇺🇸San Francisco, California, United States
Banner University Medical Center - South Campus
🇺🇸Tucson, Arizona, United States
Banner University Medical Center-Tucson Campus
🇺🇸Tucson, Arizona, United States
University of Kentucky Hospital
🇺🇸Lexington, Kentucky, United States
Kings County Hospital Center
🇺🇸Brooklyn, New York, United States
Grady Memorial Hospital
🇺🇸Atlanta, Georgia, United States
Children's Healthcare of Atlanta at Egleston
🇺🇸Atlanta, Georgia, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
University of Minnesota Medical Center
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota Masonic Children's Hospital
🇺🇸Minneapolis, Minnesota, United States
Temple University Hospital Episcopal Campus
🇺🇸Philadelphia, Pennsylvania, United States
Christiana Hospital
🇺🇸Newark, Delaware, United States
NYP Columbia University Medical Center
🇺🇸New York, New York, United States
Penn State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
University of maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
A.I.DuPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Hahnemann University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
NYP Morgan Stanley Children's Hospital
🇺🇸New York, New York, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Einstein Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Lyndon B. Johnson General Hospital
🇺🇸Houston, Texas, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
St. Louis Children's Hospital
🇺🇸Saint Louis, Missouri, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
SUNY Downstate Medical Center
🇺🇸Brooklyn, New York, United States
Maimonides Medical Center
🇺🇸Brooklyn, New York, United States
OSU Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Crozer-Chester Medical Center
🇺🇸Chester, Pennsylvania, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC Presbyterian Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Penn Presbyterian Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
University Health System University Hospital
🇺🇸San Antonio, Texas, United States
C.S. Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
UC Davis Children's Hospital
🇺🇸Sacramento, California, United States
University of Michigan Medical Center
🇺🇸Ann Arbor, Michigan, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
Detroit Receiving Hospital
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Sinai-Grace Hospital
🇺🇸Detroit, Michigan, United States
Oregon Health & Science University Hospital
🇺🇸Portland, Oregon, United States
VCU Medical Center
🇺🇸Richmond, Virginia, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Froedtert Memorial Lutheran Hospital
🇺🇸Milwaukee, Wisconsin, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
Hasbro Children's Hospital
🇺🇸Providence, Rhode Island, United States