Benzodiazepine Refractory Status EpilepticusPhase 3ESETTNCT01960075
Established Status Epilepticus Treatment Trial
A Phase 3 study testing Fosphenytoin, Levetiracetam and Valproic acid in people with Benzodiazepine Refractory Status Epilepticus, run by University of Virginia at 65 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Benzodiazepine Refractory Status Epilepticus
- What is being tested?
- Fosphenytoin, Levetiracetam and Valproic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 478 participants
- Where
- 65 sitesUnited States
- Study dates
- Oct 2015to May 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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
Trial locations and contacts
65 sites in 1 country.
65 sites in 1 country
United States65 sites
C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109
University of Michigan Medical Center
Ann Arbor, Michigan, 48109
Grady Memorial Hospital
Atlanta, Georgia, 30303
Children's Healthcare of Atlanta at Egleston
Atlanta, Georgia, 30322
University of maryland Medical Center
Baltimore, Maryland, 21201
Massachusetts General Hospital
Boston, Massachusetts, 02114
Kings County Hospital Center
Brooklyn, New York, 11203
SUNY Downstate Medical Center
Brooklyn, New York, 11203
Maimonides Medical Center
Brooklyn, New York, 11219
University of Virginia
Charlottesville, Virginia, 22908
Crozer-Chester Medical Center
Chester, Pennsylvania, 19013
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Nationwide Children's Hospital
Columbus, Ohio, 43205
OSU Wexner Medical Center
Columbus, Ohio, 43210
Children's Medical Center UTSW
Dallas, Texas, 75390
Children's Hospital of Michigan
Detroit, Michigan, 48201
Detroit Receiving Hospital
Detroit, Michigan, 48201
Henry Ford Hospital
Detroit, Michigan, 48202
Sinai-Grace Hospital
Detroit, Michigan, 48235
Fairview Southdale Hospital
Edina, Minnesota, 55435
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033
Lyndon B. Johnson General Hospital
Houston, Texas, 77026
Memorial Hermann Texas medical Center
Houston, Texas, 77030
Texas Children's Hospital
Houston, Texas, 77030
University of Kentucky Hospital
Lexington, Kentucky, 40536
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Froedtert Memorial Lutheran Hospital
Milwaukee, Wisconsin, 53226
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
University of Minnesota Medical Center
Minneapolis, Minnesota, 55454
University of Minnesota Masonic Children's Hospital
Minneapolis, Minnesota, 55455
NYP Columbia University Medical Center
New York, New York, 10032
NYP Morgan Stanley Children's Hospital
New York, New York, 10032
Christiana Hospital
Newark, Delaware, 19718
Hahnemann University Hospital
Philadelphia, Pennsylvania, 19102
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, 19104
Pennsylvania Hospital
Philadelphia, Pennsylvania, 19107
Temple University Hospital Episcopal Campus
Philadelphia, Pennsylvania, 19125
Temple University Hospital
Philadelphia, Pennsylvania, 19140
Einstein Medical Center
Philadelphia, Pennsylvania, 19141
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
UPMC Presbyterian Hospital
Pittsburgh, Pennsylvania, 15213
UPMC Mercy Hospital
Pittsburgh, Pennsylvania, 15219
Children's Hospital of Pittsburgh UPMC
Pittsburgh, Pennsylvania, 15224
Oregon Health & Science University Hospital
Portland, Oregon, 97239
Hasbro Children's Hospital
Providence, Rhode Island, 02903
Rhode Island Hospital
Providence, Rhode Island, 02903
VCU Medical Center
Richmond, Virginia, 23298
UC Davis Children's Hospital
Sacramento, California, 95817
Regions Hospital
Saint Paul, Minnesota, 55101
Primary Children's Hospital
Salt Lake City, Utah, 84113
University Health System University Hospital
San Antonio, Texas, 78229
San Francisco General Hospital
San Francisco, California, 94110
UCSF Medical Center
San Francisco, California, 94143
UCSF Benioff Children's Hospital
San Francisco, California, 94145
St. Louis Children's Hospital
St Louis, Missouri, 63110
Stanford University Medical Center
Stanford, California, 94305
Banner University Medical Center - South Campus
Tucson, Arizona, 85713
Banner University Medical Center-Tucson Campus
Tucson, Arizona, 85724
Children's National Medical Center
Washington D.C., District of Columbia, 20310
A.I.DuPont Hospital for Children
Wilmington, Delaware, 19803
About this study
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.
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.
- Being tested
- Fosphenytoin, Levetiracetam, Valproic acid
- Keywords
- status epilepticus, refractory, benzodiazepine, fosphenytoin, levetiracetam, valproic acid
- Medical subject headings
- Status Epilepticus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FosphenytoinDrug
LevetiracetamDrug
Valproic acidDrug
| Study group | Role | What they receive |
|---|---|---|
| Fosphenytoin (FOS) | Active comparator | 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. Receives: Drug: Fosphenytoin |
| Valproic acid | Active comparator | 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. Receives: Drug: Valproic acid |
| Levetiracetam | Active comparator | 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. Receives: Drug: Levetiracetam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: Within 60 minutes after the start of study drug infusion
Secondary outcomes (5)
Number of Participants With Admission to Intensive Care Unit
ICU admission is recorded as occurring only if the ICU is the initial inpatient unit for the patient.
Measured: 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
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.
Measured: 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
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.
Measured: start of drug infusion to seizure cessation
Number of Participants With Seizure Cessation Within 20 Minutes for Patients With Treatment Success
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.
Measured: within 20 minutes
Length of Hospital Stay
Length of hospital stay in days
Measured: length of hospital stay
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2013 (estimated)
- Study startOct 2015
- Primary completionFeb 2019
- Study completionMay 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Benzodiazepine Refractory Status EpilepticusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 478 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- 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)
- Responsible party
- Principal investigator, Jaideep Kapur, MD, University of Virginia
- Investigators
- Jaideep Kapur, MBBS, PhD, Study chair, University of VirginiaRobert Silbergleit, MD, Principal investigator, University of MichiganJames Chamberlain, MD, Principal investigator, Children's National Research InstituteJordan Elm, PhD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01960075
- Sponsor's protocol ID
- 18078
- Other IDs
- 119756, U01NS088034
- Acronym
- ESETT
- Status last verified
- May 2021
- First submitted
- 8 Oct 2013
- Last updated
- 14 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 24001084Cock 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.
PubMed 21967363Coralic 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.
PubMed 35718575Rosenthal 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.
PubMed 34032604Sathe 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.
PubMed 33742783Sathe 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.
PubMed 33567109Sathe 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.
PubMed 33336359Scicluna 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.
PubMed 32446674Chamberlain 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.
PubMed 32203691Kapur 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.
PubMed 31774955Sathe 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.
PubMed 31161706
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01960075
- Acronym / sponsor ID
- ESETT / 18078
- Keywords
- status epilepticus, refractory, benzodiazepine, fosphenytoin, levetiracetam, valproic acid
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 478 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- 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)
- Study start
- Oct 2015
- Primary completion
- Feb 2019 (actual)
- Study completion
- May 2019 (actual)
- First posted
- 10 Oct 2013 (estimated)
- Results
- Posted 28 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| Fosphenytoin (FOS) | Active comparator | Drug: FosphenytoinAdminister 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. |
| Valproic acid | Active comparator | Drug: Valproic acidAdminister 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. |
| Levetiracetam | Active comparator | Drug: LevetiracetamAdminister 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. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fosphenytoin | Drug | Fosphenytoin (FOS) |
| Levetiracetam | Drug | Levetiracetam |
| Valproic acid | Drug | Valproic acid |
Primary outcome
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
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
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.
5 secondary outcomes
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
Length of ICU Stay
Time frame: 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
Time frame: start of drug infusion to seizure cessation
Number of Participants With Seizure Cessation Within 20 Minutes for Patients With Treatment Success
Time frame: within 20 minutes
Length of Hospital Stay
Time frame: length of hospital stay
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24001084Bleck 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.
- Background: PubMed 21967363Cock 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.
- Derived from this study: PubMed 35718575Coralic 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.
- Derived from this study: PubMed 34032604Rosenthal 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.
- Derived from this study: PubMed 33742783Sathe 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.
- Derived from this study: PubMed 33567109Sathe 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.
- Derived from this study: PubMed 33336359Sathe 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.
- Derived from this study: PubMed 32446674Scicluna 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.
- Derived from this study: PubMed 32203691Chamberlain 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.
- Derived from this study: PubMed 31774955Kapur 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.
- Derived from this study: PubMed 31161706Sathe 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.
- ESETT WebsiteLink provided by the sponsor.
Related trials for Benzodiazepine Refractory Status Epilepticus
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jaideep Kapur, MBBS, PhD study chair
University of Virginia
Robert Silbergleit, MD principal investigator
University of Michigan
James Chamberlain, MD principal investigator
Children's National Research Institute
65 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fosphenytoin, Levetiracetam and Valproic acid in people with Benzodiazepine Refractory Status Epilepticus, run by University of Virginia at 65 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 65 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Clinical Cessation of Status Epilepticus - Intention to Treat (time frame: Within 60 minutes after the start of study drug infusion). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01960075, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2021.