ESETT
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.
Sponsor study identifier
Secondary identifiers
OTHER · ClinicalTrials.gov
NIH
interventional
478
1 country
65
Study Start
October 2015
Date type not reportedThis date has not been verified as actual or estimated.
Primary Completion
February 2019
Actual (reported)Study Completion
May 2019
Actual (reported)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.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
May 2019
Actual (reported)Click on a node to explore related trials.
Some registry-reported names shown below are not yet linked in this graph.
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
October 8, 2013
Actual (reported)October 10, 2013
Actual (reported)October 2015
Date type not reportedThis date has not been verified as actual or estimated.
February 2019
Actual (reported)May 2019
Actual (reported)February 28, 2020
Actual (reported)Number of Participants With Clinical Cessation of Status Epilepticus - Intention to Treat
Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Intention to treat
Within 60 minutes after the start of study drug infusion
Number of Participants With Clinical Cessation of Status Epilepticus - Per-protocol Analysis
Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Per-protocol analysis
Within 60 minutes after the start of study drug infusion
Number of Participants With Clinical Cessation of Status Epilepticus - Adjudicated Outcomes Analysis
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.
Within 60 minutes after the start of study drug infusion
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
Length of ICU Stay
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
Number of Participants With Seizure Cessation Within 20 Minutes for Patients With Treatment Success
within 20 minutes
Length of Hospital Stay
length of hospital stay
Number of Participants With Safety Outcome: Life Threatening Hypotension
within 60 minutes of the start of study drug infusion
Number of Participants With Safety Outcome: Life-threatening Cardiac Arrhythmia
within 60 minutes of the start of study drug infusion
Number of Participants With Safety Outcome: Endotracheal Intubation
within 60 minutes of start of study drug infusion
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.
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.
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.
Contact the study team to confirm eligibility.
Banner University Medical Center - South Campus
Tucson, Arizona, 85713, United States
Banner University Medical Center-Tucson Campus
Tucson, Arizona, 85724, United States
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095, United States
UC Davis Children's Hospital
Sacramento, California, 95817, United States
San Francisco General Hospital
San Francisco, California, 94110, United States
UCSF Medical Center
San Francisco, California, 94143, United States
UCSF Benioff Children's Hospital
Bleck T, Cock H, Chamberlain J, Cloyd J, Connor J, Elm J, Fountain N, Jones E, Lowenstein D, Shinnar S, Silbergleit R, Treiman D, Trinka E, Kapur J. The established status epilepticus trial 2013. Epilepsia. 2013 Sep;54 Suppl 6(0 6):89-92. doi: 10.1111/epi.12288.
Cock HR; ESETT Group. Established status epilepticus treatment trial (ESETT). Epilepsia. 2011 Oct;52 Suppl 8:50-2. doi: 10.1111/j.1528-1167.2011.03237.x.
Jaideep Kapur, MBBS, PhD
University of Virginia
Robert Silbergleit, MD
University of Michigan
James Chamberlain, MD
Children's National Research Institute
Jordan Elm, PhD
Medical University of South Carolina
478 participants (actual enrollment reported by the registry).
First Submitted
October 8, 2013
First Posted
October 10, 2013
Cognitive AED Outcomes in Pediatric Localization Related Epilepsy (COPE)
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
San Francisco, California, 94145, United States
Stanford University Medical Center
Stanford, California, 94305, United States
Christiana Hospital
Newark, Delaware, 19718, United States
A.I.DuPont Hospital for Children
Wilmington, Delaware, 19803, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20310, United States
Grady Memorial Hospital
Atlanta, Georgia, 30303, United States
Children's Healthcare of Atlanta at Egleston
Atlanta, Georgia, 30322, United States
University of Kentucky Hospital
Lexington, Kentucky, 40536, United States
University of maryland Medical Center
Baltimore, Maryland, 21201, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
University of Michigan Medical Center
Ann Arbor, Michigan, 48109, United States
Children's Hospital of Michigan
Detroit, Michigan, 48201, United States
Detroit Receiving Hospital
Detroit, Michigan, 48201, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Sinai-Grace Hospital
Detroit, Michigan, 48235, United States
Fairview Southdale Hospital
Edina, Minnesota, 55435, United States
Hennepin County Medical Center
Minneapolis, Minnesota, 55415, United States
University of Minnesota Medical Center
Minneapolis, Minnesota, 55454, United States
University of Minnesota Masonic Children's Hospital
Minneapolis, Minnesota, 55455, United States
Regions Hospital
Saint Paul, Minnesota, 55101, United States
St. Louis Children's Hospital
St Louis, Missouri, 63110, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Kings County Hospital Center
Brooklyn, New York, 11203, United States
SUNY Downstate Medical Center
Brooklyn, New York, 11203, United States
Maimonides Medical Center
Brooklyn, New York, 11219, United States
NYP Columbia University Medical Center
New York, New York, 10032, United States
NYP Morgan Stanley Children's Hospital
New York, New York, 10032, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
OSU Wexner Medical Center
Columbus, Ohio, 43210, United States
Oregon Health & Science University Hospital
Portland, Oregon, 97239, United States
Crozer-Chester Medical Center
Chester, Pennsylvania, 19013, United States
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
Hahnemann University Hospital
Philadelphia, Pennsylvania, 19102, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, 19104, United States
Pennsylvania Hospital
Philadelphia, Pennsylvania, 19107, United States
Temple University Hospital Episcopal Campus
Philadelphia, Pennsylvania, 19125, United States
Temple University Hospital
Philadelphia, Pennsylvania, 19140, United States
Einstein Medical Center
Philadelphia, Pennsylvania, 19141, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212, United States
UPMC Presbyterian Hospital
Pittsburgh, Pennsylvania, 15213, United States
UPMC Mercy Hospital
Pittsburgh, Pennsylvania, 15219, United States
Children's Hospital of Pittsburgh UPMC
Pittsburgh, Pennsylvania, 15224, United States
Hasbro Children's Hospital
Providence, Rhode Island, 02903, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Children's Medical Center UTSW
Dallas, Texas, 75390, United States
Lyndon B. Johnson General Hospital
Houston, Texas, 77026, United States
Memorial Hermann Texas medical Center
Houston, Texas, 77030, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
University Health System University Hospital
San Antonio, Texas, 78229, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
University of Virginia
Charlottesville, Virginia, 22908, United States
VCU Medical Center
Richmond, Virginia, 23298, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Froedtert Memorial Lutheran Hospital
Milwaukee, Wisconsin, 53226, United States
Coralic Z, Kapur J, Olson KR, Chamberlain JM, Overbeek D, Silbergleit R. Treatment of Toxin-Related Status Epilepticus With Levetiracetam, Fosphenytoin, or Valproate in Patients Enrolled in the Established Status Epilepticus Treatment Trial. Ann Emerg Med. 2022 Sep;80(3):194-202. doi: 10.1016/j.annemergmed.2022.04.020. Epub 2022 Jun 17.
Rosenthal ES, Elm JJ, Ingles J, Rogers AJ, Terndrup TE, Holsti M, Thomas DG, Babcock L, Okada PJ, Lipsky RH, Miller JB, Hickey RW, Barra ME, Bleck TP, Cloyd JC, Silbergleit R, Lowenstein DH, Coles LD, Kapur J, Shinnar S, Chamberlain JM; Established Status Epilepticus Treatment Trial Study Group. Early Neurologic Recovery, Practice Pattern Variation, and the Risk of Endotracheal Intubation Following Established Status Epilepticus. Neurology. 2021 May 11;96(19):e2372-e2386. doi: 10.1212/WNL.0000000000011879. Epub 2021 Mar 23.
Sathe AG, Brundage RC, Ivaturi V, Cloyd JC, Chamberlain JM, Elm JJ, Silbergleit R, Kapur J, Coles LD. A pharmacokinetic simulation study to assess the performance of a sparse blood sampling approach to quantify early drug exposure. Clin Transl Sci. 2021 Jul;14(4):1444-1451. doi: 10.1111/cts.13004. Epub 2021 May 1.
Sathe AG, Underwood E, Coles LD, Elm JJ, Silbergleit R, Chamberlain JM, Kapur J, Cock HR, Fountain NB, Shinnar S, Lowenstein DH, Rosenthal ES, Conwit RA, Bleck TP, Cloyd JC. Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial. Epilepsia. 2021 Mar;62(3):795-806. doi: 10.1111/epi.16825. Epub 2021 Feb 10.
Sathe AG, Mishra U, Ivaturi V, Brundage RC, Cloyd JC, Elm JJ, Chamberlain JM, Silbergleit R, Kapur J, Lowenstein DH, Shinnar S, Cock HR, Fountain NB, Babcock L, Coles LD. Early Exposure of Fosphenytoin, Levetiracetam, and Valproic Acid After High-Dose Intravenous Administration in Young Children With Benzodiazepine-Refractory Status Epilepticus. J Clin Pharmacol. 2021 Jun;61(6):763-768. doi: 10.1002/jcph.1801. Epub 2021 Jan 12.
Scicluna VM, Biros M, Harney DK, Jones EB, Mitchell AR, Pentz RD, Silbergleit R, Speight CD, Wright DW, Dickert NW. Patient and Surrogate Postenrollment Perspectives on Research Using the Exception From Informed Consent: An Integrated Survey. Ann Emerg Med. 2020 Sep;76(3):343-349. doi: 10.1016/j.annemergmed.2020.03.017. Epub 2020 May 21.
Chamberlain JM, Kapur J, Shinnar S, Elm J, Holsti M, Babcock L, Rogers A, Barsan W, Cloyd J, Lowenstein D, Bleck TP, Conwit R, Meinzer C, Cock H, Fountain NB, Underwood E, Connor JT, Silbergleit R; Neurological Emergencies Treatment Trials; Pediatric Emergency Care Applied Research Network investigators. Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trial. Lancet. 2020 Apr 11;395(10231):1217-1224. doi: 10.1016/S0140-6736(20)30611-5. Epub 2020 Mar 20.
Kapur J, Elm J, Chamberlain JM, Barsan W, Cloyd J, Lowenstein D, Shinnar S, Conwit R, Meinzer C, Cock H, Fountain N, Connor JT, Silbergleit R; NETT and PECARN Investigators. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. N Engl J Med. 2019 Nov 28;381(22):2103-2113. doi: 10.1056/NEJMoa1905795.
Sathe AG, Tillman H, Coles LD, Elm JJ, Silbergleit R, Chamberlain J, Kapur J, Cock HR, Fountain NB, Shinnar S, Lowenstein DH, Conwit RA, Bleck TP, Cloyd JC. Underdosing of Benzodiazepines in Patients With Status Epilepticus Enrolled in Established Status Epilepticus Treatment Trial. Acad Emerg Med. 2019 Aug;26(8):940-943. doi: 10.1111/acem.13811. Epub 2019 Jul 18. No abstract available.
Study Start
October 2015
Date type not reportedThis date has not been verified as actual or estimated.
Primary Completion
February 2019
Actual (reported)Study Completion
May 2019
Actual (reported)Last Updated
June 14, 2021
Results First Posted
February 28, 2020
Record last verified: 2021-05
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