Evidence map›Paper›PMID 31774955›Full record

Trial reportThe New England journal of medicine2019

Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus.

Jaideep Kapur, Jordan Elm, James M Chamberlain, William Barsan, James Cloyd, Daniel Lowenstein, Shlomo Shinnar, Robin Conwit, Caitlyn Meinzer, Hannah Cock and 4 more

Registry-linked trialOpen access · bronzeAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01960075 (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.), which is not on this map. Cited by 191 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
191citing papers in PubMed, 12 pooled it
46.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01960075 phase3completednot on this map

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.

TypeinterventionalSponsorUniversity of VirginiaRan2015 to 2019Enrolled478ConditionsBenzodiazepine Refractory Status EpilepticusArmsFosphenytoin, Levetiracetam, Valproic acid
3 · Its place in the literature

Who cites it

191 citing papers in PubMed, 12 syntheses or guidelines pooled it, 531 citations in OpenAlex.

  1. Pooled it
  2. Neuropsychiatric Adverse Effects Associated with the Use of Levetiracetam in Adults: A Systematic Review and Meta-Analysis.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2026
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  13. Chronological Sequence of Convulsive Status Epilepticus Treatment Steps in a Real-Life Scenario for Patients Enrolled in a Large Multicenter Trial.Academic emergency medicine : official journal of the Society for Academic Emergency Medicine · 2026
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131 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 2 countries.

Jaideep KapurFrom the Department of Neurology, University of Virginia, Charlottesville (J.K., N.F.); the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.E., C.M.); the Division of Emergency Medicine, Children's National Medical Center, Washington, DC (J.M.C.); the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B., R.S.); the College of Pharmacy, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis (J.C.); the Department of Neurology, University of California, San Francisco, San Francisco (D.L.); the Departments of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York (S.S.); the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (R.C.); St. George's University of London and St. George's University Hospitals NHS Foundation Trust, London (H.C.); and ConfluenceStat (J.T.C.) and the University of Central Florida College of Medicine (J.T.C.) - both in Orlando.
Jordan ElmFrom the Department of Neurology, University of Virginia, Charlottesville (J.K., N.F.); the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.E., C.M.); the Division of Emergency Medicine, Children's National Medical Center, Washington, DC (J.M.C.); the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B., R.S.); the College of Pharmacy, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis (J.C.); the Department of Neurology, University of California, San Francisco, San Francisco (D.L.); the Departments of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York (S.S.); the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (R.C.); St. George's University of London and St. George's University Hospitals NHS Foundation Trust, London (H.C.); and ConfluenceStat (J.T.C.) and the University of Central Florida College of Medicine (J.T.C.) - both in Orlando.
James M ChamberlainFrom the Department of Neurology, University of Virginia, Charlottesville (J.K., N.F.); the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.E., C.M.); the Division of Emergency Medicine, Children's National Medical Center, Washington, DC (J.M.C.); the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B., R.S.); the College of Pharmacy, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis (J.C.); the Department of Neurology, University of California, San Francisco, San Francisco (D.L.); the Departments of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York (S.S.); the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (R.C.); St. George's University of London and St. George's University Hospitals NHS Foundation Trust, London (H.C.); and ConfluenceStat (J.T.C.) and the University of Central Florida College of Medicine (J.T.C.) - both in Orlando.
William BarsanFrom the Department of Neurology, University of Virginia, Charlottesville (J.K., N.F.); the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.E., C.M.); the Division of Emergency Medicine, Children's National Medical Center, Washington, DC (J.M.C.); the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B., R.S.); the College of Pharmacy, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis (J.C.); the Department of Neurology, University of California, San Francisco, San Francisco (D.L.); the Departments of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York (S.S.); the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (R.C.); St. George's University of London and St. George's University Hospitals NHS Foundation Trust, London (H.C.); and ConfluenceStat (J.T.C.) and the University of Central Florida College of Medicine (J.T.C.) - both in Orlando.
James CloydFrom the Department of Neurology, University of Virginia, Charlottesville (J.K., N.F.); the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.E., C.M.); the Division of Emergency Medicine, Children's National Medical Center, Washington, DC (J.M.C.); the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B., R.S.); the College of Pharmacy, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis (J.C.); the Department of Neurology, University of California, San Francisco, San Francisco (D.L.); the Departments of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York (S.S.); the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (R.C.); St. George's University of London and St. George's University Hospitals NHS Foundation Trust, London (H.C.); and ConfluenceStat (J.T.C.) and the University of Central Florida College of Medicine (J.T.C.) - both in Orlando.
Daniel LowensteinFrom the Department of Neurology, University of Virginia, Charlottesville (J.K., N.F.); the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.E., C.M.); the Division of Emergency Medicine, Children's National Medical Center, Washington, DC (J.M.C.); the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B., R.S.); the College of Pharmacy, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis (J.C.); the Department of Neurology, University of California, San Francisco, San Francisco (D.L.); the Departments of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York (S.S.); the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (R.C.); St. George's University of London and St. George's University Hospitals NHS Foundation Trust, London (H.C.); and ConfluenceStat (J.T.C.) and the University of Central Florida College of Medicine (J.T.C.) - both in Orlando.
Shlomo ShinnarFrom the Department of Neurology, University of Virginia, Charlottesville (J.K., N.F.); the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.E., C.M.); the Division of Emergency Medicine, Children's National Medical Center, Washington, DC (J.M.C.); the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B., R.S.); the College of Pharmacy, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis (J.C.); the Department of Neurology, University of California, San Francisco, San Francisco (D.L.); the Departments of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York (S.S.); the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (R.C.); St. George's University of London and St. George's University Hospitals NHS Foundation Trust, London (H.C.); and ConfluenceStat (J.T.C.) and the University of Central Florida College of Medicine (J.T.C.) - both in Orlando.
Robin ConwitFrom the Department of Neurology, University of Virginia, Charlottesville (J.K., N.F.); the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.E., C.M.); the Division of Emergency Medicine, Children's National Medical Center, Washington, DC (J.M.C.); the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B., R.S.); the College of Pharmacy, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis (J.C.); the Department of Neurology, University of California, San Francisco, San Francisco (D.L.); the Departments of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York (S.S.); the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (R.C.); St. George's University of London and St. George's University Hospitals NHS Foundation Trust, London (H.C.); and ConfluenceStat (J.T.C.) and the University of Central Florida College of Medicine (J.T.C.) - both in Orlando.
Caitlyn MeinzerFrom the Department of Neurology, University of Virginia, Charlottesville (J.K., N.F.); the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.E., C.M.); the Division of Emergency Medicine, Children's National Medical Center, Washington, DC (J.M.C.); the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B., R.S.); the College of Pharmacy, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis (J.C.); the Department of Neurology, University of California, San Francisco, San Francisco (D.L.); the Departments of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York (S.S.); the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (R.C.); St. George's University of London and St. George's University Hospitals NHS Foundation Trust, London (H.C.); and ConfluenceStat (J.T.C.) and the University of Central Florida College of Medicine (J.T.C.) - both in Orlando.
Hannah CockFrom the Department of Neurology, University of Virginia, Charlottesville (J.K., N.F.); the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.E., C.M.); the Division of Emergency Medicine, Children's National Medical Center, Washington, DC (J.M.C.); the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B., R.S.); the College of Pharmacy, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis (J.C.); the Department of Neurology, University of California, San Francisco, San Francisco (D.L.); the Departments of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York (S.S.); the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (R.C.); St. George's University of London and St. George's University Hospitals NHS Foundation Trust, London (H.C.); and ConfluenceStat (J.T.C.) and the University of Central Florida College of Medicine (J.T.C.) - both in Orlando.
Nathan FountainFrom the Department of Neurology, University of Virginia, Charlottesville (J.K., N.F.); the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.E., C.M.); the Division of Emergency Medicine, Children's National Medical Center, Washington, DC (J.M.C.); the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B., R.S.); the College of Pharmacy, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis (J.C.); the Department of Neurology, University of California, San Francisco, San Francisco (D.L.); the Departments of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York (S.S.); the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (R.C.); St. George's University of London and St. George's University Hospitals NHS Foundation Trust, London (H.C.); and ConfluenceStat (J.T.C.) and the University of Central Florida College of Medicine (J.T.C.) - both in Orlando.
Jason T ConnorFrom the Department of Neurology, University of Virginia, Charlottesville (J.K., N.F.); the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.E., C.M.); the Division of Emergency Medicine, Children's National Medical Center, Washington, DC (J.M.C.); the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B., R.S.); the College of Pharmacy, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis (J.C.); the Department of Neurology, University of California, San Francisco, San Francisco (D.L.); the Departments of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York (S.S.); the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (R.C.); St. George's University of London and St. George's University Hospitals NHS Foundation Trust, London (H.C.); and ConfluenceStat (J.T.C.) and the University of Central Florida College of Medicine (J.T.C.) - both in Orlando.
Robert SilbergleitFrom the Department of Neurology, University of Virginia, Charlottesville (J.K., N.F.); the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.E., C.M.); the Division of Emergency Medicine, Children's National Medical Center, Washington, DC (J.M.C.); the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B., R.S.); the College of Pharmacy, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis (J.C.); the Department of Neurology, University of California, San Francisco, San Francisco (D.L.); the Departments of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York (S.S.); the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (R.C.); St. George's University of London and St. George's University Hospitals NHS Foundation Trust, London (H.C.); and ConfluenceStat (J.T.C.) and the University of Central Florida College of Medicine (J.T.C.) - both in Orlando.ORCID 0000-0003-4101-2430
NETT and PECARN Investigators
Medical University of South Carolina · USAlbert Einstein College of Medicine · USChildren's National · USNational Institutes of Health · USUniversity of Central Florida · USUniversity of Minnesota · US

Funding

Neurologic Emergencies Treatment Trials Network: Clinical Coordinating CenterU01NS056975 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BARSAN, WILLIAM G · 2006 to 2015
$40.4M
Established Status Epilepticus Treatment Trial (ESETT)U01NS088034 · NINDS · UNIVERSITY OF VIRGINIA · PI CHAMBERLAIN, JAMES, KAPUR, JAIDEEP · 2014 to 2018
$16.3M
Neurological Emergencies Treatment Trials Network Statistical and Data ManagementU01NS059041 · NINDS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI DURKALSKI, VALERIE L, PALESCH, YUKO Y · 2006 to 2015
$9.1M
Established Status Epilepticus Treatment Trial (ESETT) - SDMCU01NS088023 · NINDS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ELM, JORDAN J. · 2014 to 2018
$2.0M
Accelerating Drug and Device Evaluation through Innovative Clinical Trial DesignU01NS073476 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BARSAN, WILLIAM G, BERRY, DONALD A · 2010 to 2012
$2.0M
The Boston NETT GroupU10NS080369 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI GOLDSTEIN, JOSHUA N · 2012 to 2016
$1.6M
The Mass-SIREN GroupU24NS100651 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI GOLDSTEIN, JOSHUA N · 2017 to 2022
$1.1M
NINDS NIH HHS U01 NS056975NINDS NIH HHS U01NS056975NINDS NIH HHS U01 NS059041NINDS NIH HHS U01NS059041NINDS NIH HHS U01 NS073476NINDS NIH HHS U01NS073476NINDS NIH HHS U01 NS088023NINDS NIH HHS U01NS088023NINDS NIH HHS U01 NS088034NINDS NIH HHS U01NS088034NINDS NIH HHS U10 NS080369NINDS NIH HHS U24 NS100651
6 · The paper itself

Abstract

backgroundThe choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied.

methodsIn a randomized, blinded, adaptive trial, we compared the efficacy and safety of three intravenous anticonvulsive agents - levetiracetam, fosphenytoin, and valproate - in children and adults with convulsive status epilepticus that was unresponsive to treatment with benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication. The posterior probabilities that each drug was the most or least effective were calculated. Safety outcomes included life-threatening hypotension or cardiac arrhythmia, endotracheal intubation, seizure recurrence, and death.

resultsA total of 384 patients were enrolled and randomly assigned to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121). Reenrollment of patients with a second episode of status epilepticus accounted for 16 additional instances of randomization. In accordance with a prespecified stopping rule for futility of finding one drug to be superior or inferior, a planned interim analysis led to the trial being stopped. Of the enrolled patients, 10% were determined to have had psychogenic seizures. The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 68 patients assigned to levetiracetam (47%; 95% credible interval, 39 to 55), 53 patients assigned to fosphenytoin (45%; 95% credible interval, 36 to 54), and 56 patients assigned to valproate (46%; 95% credible interval, 38 to 55). The posterior probability that each drug was the most effective was 0.41, 0.24, and 0.35, respectively. Numerically more episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant.

conclusionsIn the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, and valproate each led to seizure cessation and improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ESETT ClinicalTrials.gov number, NCT01960075.).

Indexed as

AdolescentAdultAnticonvulsantsBenzodiazepinesChildChild, PreschoolDouble-Blind MethodDrug ResistanceFemaleHumansHypotensionInfusions, IntravenousInjections, IntramuscularLevetiracetamMaleMiddle AgedAnticonvulsantsBenzodiazepinesfosphenytoinLevetiracetamPhenytoinValproic Acid

Identifiers

PMID31774955
PMCPMC7098487
OpenAlexW2991266411

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.