Levetiracetam Versus Phenobarbital for Neonatal Seizures: A Randomized Controlled Trial.

Anticonvulsants / therapeutic use Dose-Response Relationship, Drug Double-Blind Method Epilepsy, Benign Neonatal / diagnosis Female Humans Infant, Newborn Levetiracetam / therapeutic use Male Phenobarbital / therapeutic use Seizures / diagnosis

Journal

Pediatrics
ISSN: 1098-4275
Titre abrégé: Pediatrics
Pays: United States
ID NLM: 0376422

Informations de publication

Date de publication:
06 2020
Historique:
accepted: 16 03 2020
pubmed: 10 5 2020
medline: 13 8 2020
entrez: 10 5 2020
Statut: ppublish

Résumé

There are no US Food and Drug Administration-approved therapies for neonatal seizures. Phenobarbital and phenytoin frequently fail to control seizures. There are concerns about the safety of seizure medications in the developing brain. Levetiracetam has proven efficacy and an excellent safety profile in older patients; therefore, there is great interest in its use in neonates. However, randomized studies have not been performed. Our objectives were to study the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment of neonatal seizures. The study was a multicenter, randomized, blinded, controlled, phase IIb trial investigating the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment for neonatal seizures of any cause. The primary outcome measure was complete seizure freedom for 24 hours, assessed by independent review of the EEGs by 2 neurophysiologists. Eighty percent of patients (24 of 30) randomly assigned to phenobarbital remained seizure free for 24 hours, compared with 28% of patients (15 of 53) randomly assigned to levetiracetam ( In this phase IIb study, phenobarbital was more effective than levetiracetam for the treatment of neonatal seizures. Higher rates of adverse effects were seen with phenobarbital treatment. Higher-dose studies of levetiracetam are warranted, and definitive studies with long-term outcome measures are needed.

Sections du résumé

BACKGROUND AND OBJECTIVES
There are no US Food and Drug Administration-approved therapies for neonatal seizures. Phenobarbital and phenytoin frequently fail to control seizures. There are concerns about the safety of seizure medications in the developing brain. Levetiracetam has proven efficacy and an excellent safety profile in older patients; therefore, there is great interest in its use in neonates. However, randomized studies have not been performed. Our objectives were to study the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment of neonatal seizures.
METHODS
The study was a multicenter, randomized, blinded, controlled, phase IIb trial investigating the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment for neonatal seizures of any cause. The primary outcome measure was complete seizure freedom for 24 hours, assessed by independent review of the EEGs by 2 neurophysiologists.
RESULTS
Eighty percent of patients (24 of 30) randomly assigned to phenobarbital remained seizure free for 24 hours, compared with 28% of patients (15 of 53) randomly assigned to levetiracetam (
CONCLUSIONS
In this phase IIb study, phenobarbital was more effective than levetiracetam for the treatment of neonatal seizures. Higher rates of adverse effects were seen with phenobarbital treatment. Higher-dose studies of levetiracetam are warranted, and definitive studies with long-term outcome measures are needed.

Identifiants

DOI: 10.1542/peds.2019-3182 PMID: 32385134 PMC: PMC7263056
pubmed: 32385134
pii: peds.2019-3182
doi: 10.1542/peds.2019-3182
pmc: PMC7263056
pii:
doi:

Substances chimiques

Anticonvulsants 0
Levetiracetam 44YRR34555
Phenobarbital YQE403BP4D

Types de publication

Clinical Trial, Phase II Comparative Study Journal Article Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : FDA HHS
ID : R01 FD004147
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001442
Pays : United States

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © 2020 by the American Academy of Pediatrics.

Déclaration de conflit d'intérêts

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

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Auteurs

Cynthia Sharpe (C)

Department of Paediatric Neurology, Starship Children's Health, Auckland, New Zealand.
Department of Neurosciences, School of Medicine, University of California, San Diego and Rady Children's Hospital-San Diego, San Diego, California.

Gail E Reiner (GE)

Department of Neurosciences, School of Medicine, University of California, San Diego and Rady Children's Hospital-San Diego, San Diego, California.

Suzanne L Davis (SL)

Department of Paediatric Neurology, Starship Children's Health, Auckland, New Zealand.

Mark Nespeca (M)

Department of Neurosciences, School of Medicine, University of California, San Diego and Rady Children's Hospital-San Diego, San Diego, California.

Jeffrey J Gold (JJ)

Department of Neurosciences, School of Medicine, University of California, San Diego and Rady Children's Hospital-San Diego, San Diego, California.

Maynard Rasmussen (M)

San Diego Neonatology Inc and.

Rachel Kuperman (R)

Pediatric Neurology, University of California, San Francisco Benioff Children's Hospital Oakland, Oakland, California.

Mary Jo Harbert (MJ)

Department of Neurosciences, School of Medicine, University of California, San Diego and Sharp Mary Birch Hospital for Women & Newborns, San Diego, California.

David Michelson (D)

Division of Pediatric Neurology, Department of Pediatrics, Loma Linda University Children's Hospital, Loma Linda, California.

Priscilla Joe (P)

Division of Neonatology, Departments of Pediatrics and.

Sonya Wang (S)

Department of Neurosciences, School of Medicine, University of California, San Diego and Rady Children's Hospital-San Diego, San Diego, California.

Neggy Rismanchi (N)

Department of Neurosciences, School of Medicine, University of California, San Diego and Rady Children's Hospital-San Diego, San Diego, California.

Ngoc Minh Le (NM)

Neonatal Research Institute, Sharp Mary Birch Hospital for Women & Newborns, San Diego, California.

Andrew Mower (A)

Department of Neurology, Children's Hospital of Orange County, Orange, California.

Jae Kim (J)

Division of NeoNatology, Departments of Pediatrics and.

Malcolm R Battin (MR)

Department of Neonatology, Auckland District Health Board, Auckland, New Zealand; and.

Brian Lane (B)

Division of Neonatology, Departments of Pediatrics, University of California, San Diego and Rady Children's Hospital San Diego, San Diego, California.

Jose Honold (J)

Division of Neonatology, Departments of Pediatrics, University of California, San Diego and Rady Children's Hospital San Diego, San Diego, California.

Ellen Knodel (E)

Division of Neonatology, Departments of Pediatrics, University of California, San Diego and Rady Children's Hospital San Diego, San Diego, California.

Kathy Arnell (K)

Neonatal Research Institute, Sharp Mary Birch Hospital for Women & Newborns, San Diego, California.

Renee Bridge (R)

Division of NeoNatology, Departments of Pediatrics and.

Lilly Lee (L)

Neurosciences, School of Medicine, University of California, San Diego, San Diego, California.

Karin Ernstrom (K)

Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, Los Angeles, California.

Rema Raman (R)

Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, Los Angeles, California.

Richard H Haas (RH)

Department of Neurosciences, School of Medicine, University of California, San Diego and Rady Children's Hospital-San Diego, San Diego, California; rhaas@health.ucsd.edu.

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents du système nerveux central › Anticonvulsivants › Levetiracetam Versus Phenobarbital for...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes toxicologiques › Relation dose-effet des médicaments › Levetiracetam Versus Phenobarbital for...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méthode en double aveugle › Levetiracetam Versus Phenobarbital for...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies néonatales › Épilepsie bénigne néonatale › Levetiracetam Versus Phenobarbital for...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Levetiracetam Versus Phenobarbital for...
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questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyrrolidines › Pyrrolidones › Lévétiracétam › Levetiracetam Versus Phenobarbital for...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyrimidines › Pyrimidinones › Barbituriques › Phénobarbital › Levetiracetam Versus Phenobarbital for...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Crises épileptiques › Levetiracetam Versus Phenobarbital for...