Established Status Epilepticus Treatment Trial

NCT ID: NCT01960075

Last Updated: 2021-06-14

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

478 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-31

Study Completion Date

2019-05-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Benzodiazepine Refractory Status Epilepticus

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type ACTIVE_COMPARATOR

Fosphenytoin

Intervention Type DRUG

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.

Group Type ACTIVE_COMPARATOR

Valproic acid

Intervention Type DRUG

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.

Group Type ACTIVE_COMPARATOR

Levetiracetam

Intervention Type DRUG

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Fosphenytoin

Intervention Type DRUG

Levetiracetam

Intervention Type DRUG

Valproic acid

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion 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
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Michigan

OTHER

Sponsor Role collaborator

Medical University of South Carolina

OTHER

Sponsor Role collaborator

Children's National Research Institute

OTHER

Sponsor Role collaborator

University of Minnesota

OTHER

Sponsor Role collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

University of Virginia

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Jaideep Kapur, MD

Professor of Neurology and Neuroscience

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Jaideep Kapur, MBBS, PhD

Role: STUDY_CHAIR

University of Virginia

Robert Silbergleit, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

James Chamberlain, MD

Role: PRINCIPAL_INVESTIGATOR

Children's National Research Institute

Jordan Elm, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Banner University Medical Center - South Campus

Tucson, Arizona, United States

Site Status

Banner University Medical Center-Tucson Campus

Tucson, Arizona, United States

Site Status

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

Site Status

UC Davis Children's Hospital

Sacramento, California, United States

Site Status

San Francisco General Hospital

San Francisco, California, United States

Site Status

UCSF Medical Center

San Francisco, California, United States

Site Status

UCSF Benioff Children's Hospital

San Francisco, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

Christiana Hospital

Newark, Delaware, United States

Site Status

A.I.DuPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Grady Memorial Hospital

Atlanta, Georgia, United States

Site Status

Children's Healthcare of Atlanta at Egleston

Atlanta, Georgia, United States

Site Status

University of Kentucky Hospital

Lexington, Kentucky, United States

Site Status

University of maryland Medical Center

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

C.S. Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

Detroit Receiving Hospital

Detroit, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Sinai-Grace Hospital

Detroit, Michigan, United States

Site Status

Fairview Southdale Hospital

Edina, Minnesota, United States

Site Status

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Masonic Children's Hospital

Minneapolis, Minnesota, United States

Site Status

Regions Hospital

Saint Paul, Minnesota, United States

Site Status

St. Louis Children's Hospital

St Louis, Missouri, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Kings County Hospital Center

Brooklyn, New York, United States

Site Status

SUNY Downstate Medical Center

Brooklyn, New York, United States

Site Status

Maimonides Medical Center

Brooklyn, New York, United States

Site Status

NYP Columbia University Medical Center

New York, New York, United States

Site Status

NYP Morgan Stanley Children's Hospital

New York, New York, United States

Site Status

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

OSU Wexner Medical Center

Columbus, Ohio, United States

Site Status

Oregon Health & Science University Hospital

Portland, Oregon, United States

Site Status

Crozer-Chester Medical Center

Chester, Pennsylvania, United States

Site Status

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Hahnemann University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Site Status

Temple University Hospital Episcopal Campus

Philadelphia, Pennsylvania, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Einstein Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Mercy Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Hasbro Children's Hospital

Providence, Rhode Island, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Children's Medical Center UTSW

Dallas, Texas, United States

Site Status

Lyndon B. Johnson General Hospital

Houston, Texas, United States

Site Status

Memorial Hermann Texas medical Center

Houston, Texas, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

University Health System University Hospital

San Antonio, Texas, United States

Site Status

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

VCU Medical Center

Richmond, Virginia, United States

Site Status

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 24001084 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21967363 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35718575 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34032604 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33742783 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33567109 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33336359 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32446674 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32203691 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31774955 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31161706 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

119756

Identifier Type: OTHER

Identifier Source: secondary_id

U01NS088034

Identifier Type: NIH

Identifier Source: secondary_id

View Link

18078

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.