Evidence map›Paper›PMID 27986874›Full record

Trial reportNeurology2017

Second monotherapy in childhood absence epilepsy.

Avital Cnaan, Shlomo Shinnar, Ravindra Arya, Peter C Adamson, Peggy O Clark, Dennis Dlugos, Deborah G Hirtz, David Masur, Tracy A Glauser, Childhood Absence Epilepsy Study Group

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

Trial report in Neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00088452 (Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study), which is not on this map. Cited by 20 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 2 pooled it
1.6field-weighted citation impact, top 16% 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.

NCT00088452 phase3completednot on this map

Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study

TypeinterventionalSponsorChildren's Hospital Medical Center, CincinnatiRan2004 to 2016Enrolled453ConditionsChildhood Absence Epilepsy, Petit Mal Epilepsy, Epilepsy, SeizuresArmsEthosuximide, Lamotrigine, Valproic acid
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
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  6. Article
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  9. Review
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  14. Review
  15. Article
  16. Article
  17. Review
  18. Absence Seizures in Children: Usual and the Unusual.Indian journal of pediatrics · 2020
    Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Avital CnaanFrom Children's National Health System (A.C.), Washington, DC; Montefiore Medical Center (S.S., D.M.), Albert Einstein College of Medicine, New York, NY; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (R.A., P.O.C., T.A.G.), OH; The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania (P.C.A., D.D.); and National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD. acnaan@trinds.com.
Shlomo ShinnarFrom Children's National Health System (A.C.), Washington, DC; Montefiore Medical Center (S.S., D.M.), Albert Einstein College of Medicine, New York, NY; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (R.A., P.O.C., T.A.G.), OH; The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania (P.C.A., D.D.); and National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD.
Ravindra AryaFrom Children's National Health System (A.C.), Washington, DC; Montefiore Medical Center (S.S., D.M.), Albert Einstein College of Medicine, New York, NY; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (R.A., P.O.C., T.A.G.), OH; The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania (P.C.A., D.D.); and National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD.
Peter C AdamsonFrom Children's National Health System (A.C.), Washington, DC; Montefiore Medical Center (S.S., D.M.), Albert Einstein College of Medicine, New York, NY; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (R.A., P.O.C., T.A.G.), OH; The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania (P.C.A., D.D.); and National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD.
Peggy O ClarkFrom Children's National Health System (A.C.), Washington, DC; Montefiore Medical Center (S.S., D.M.), Albert Einstein College of Medicine, New York, NY; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (R.A., P.O.C., T.A.G.), OH; The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania (P.C.A., D.D.); and National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD.
Dennis DlugosFrom Children's National Health System (A.C.), Washington, DC; Montefiore Medical Center (S.S., D.M.), Albert Einstein College of Medicine, New York, NY; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (R.A., P.O.C., T.A.G.), OH; The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania (P.C.A., D.D.); and National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD.
Deborah G HirtzFrom Children's National Health System (A.C.), Washington, DC; Montefiore Medical Center (S.S., D.M.), Albert Einstein College of Medicine, New York, NY; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (R.A., P.O.C., T.A.G.), OH; The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania (P.C.A., D.D.); and National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD.
David MasurFrom Children's National Health System (A.C.), Washington, DC; Montefiore Medical Center (S.S., D.M.), Albert Einstein College of Medicine, New York, NY; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (R.A., P.O.C., T.A.G.), OH; The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania (P.C.A., D.D.); and National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD.
Tracy A GlauserFrom Children's National Health System (A.C.), Washington, DC; Montefiore Medical Center (S.S., D.M.), Albert Einstein College of Medicine, New York, NY; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (R.A., P.O.C., T.A.G.), OH; The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania (P.C.A., D.D.); and National Institute of Neurological Disorders and Stroke (D.G.H.), Bethesda, MD.
Childhood Absence Epilepsy Study Group
Children's National · US

Funding

Impact of Initial Therapy and Response on Long Term Outcome in Children with CAEU01NS045911 · NINDS · CINCINNATI CHILDRENS HOSP MED CTR · PI GLAUSER, TRACY A · 2003 to 2013
$31.1M
The Epilepsy Phenome/ Genome Project (EPGP)U01NS053998 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOWENSTEIN, DANIEL H · 2007 to 2013
$26.4M
Core-010UL1TR001073 · NCATS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI KELLER, MARLA J, SHAMOON, HARRY · 2013 to 2017
$21.3M
Established Status Epilepticus Treatment Trial (ESETT)U01NS088034 · NINDS · UNIVERSITY OF VIRGINIA · PI CHAMBERLAIN, JAMES, KAPUR, JAIDEEP · 2014 to 2018
$16.3M
NEUROIMAGING COREP30HD040677 · NICHD · CHILDREN'S RESEARCH INSTITUTE · PI MCCARTER, ROBERT JAMES · 2001 to 2015
$15.9M
Consequences of Prolonged Febrile Seizures in ChildhoodR37NS043209 · NINDS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI SHINNAR, SHLOMO · 2013 to 2019
$11.4M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR031988 · NCRR · CHILDREN'S RESEARCH INSTITUTE · PI JOSEPH, JILL G · 2010 to 2011
$8.2M
RNA fidelity and protein function of Becker-like in-frame deletionsP50AR060836 · NIAMS · CHILDREN'S RESEARCH INSTITUTE · PI PARTRIDGE, TERENCE A · 2011 to 2015
$7.8M
N-carbamylglutamate in the treatment of hyperammonemiaR01HD058567 · NICHD · CHILDREN'S RESEARCH INSTITUTE · PI TUCHMAN, MENDEL · 2008 to 2016
$4.4M
Childhood Absence Epilepsy: Coordinating CenterU01NS045803 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI CNAAN, AVITAL · 2003 to 2008
$4.0M
2 of 7 EPI4K - Phenotyping Clinical Informatics Core U01NS077276 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOWENSTEIN, DANIEL H · 2011 to 2015
$3.1M
Imaging the effect of centrotemporal spikes and seizures on language in childrenR01NS065840 · NINDS · CINCINNATI CHILDRENS HOSP MED CTR · PI VANNEST, JENNIFER J. · 2011 to 2015
$2.5M
NCATS NIH HHS UL1 TR001073NCRR NIH HHS UL1 RR031988NIAMS NIH HHS P50 AR060836NIAMS NIH HHS R01 AR061875NICHD NIH HHS P30 HD040677NICHD NIH HHS R01 HD058567NINDS NIH HHS R01 NS062756NINDS NIH HHS R01 NS065840NINDS NIH HHS R37 NS043209NINDS NIH HHS U01 NS045803NINDS NIH HHS U01 NS045911NINDS NIH HHS U01 NS053998NINDS NIH HHS U01 NS077276NINDS NIH HHS U01 NS088034NINDS NIH HHS U10 NS077308NINDS NIH HHS U10 NS077311NLM NIH HHS R01 LM011124
6 · The paper itself

Abstract

objectiveTo determine optimal second monotherapy for children with childhood absence epilepsy (CAE) experiencing initial treatment failure.

methodsChildren with CAE experiencing treatment failure during the double-blind phase of a randomized controlled trial comparing ethosuximide, valproic acid, and lamotrigine were randomized to open-label second monotherapy with one of the 2 other study therapies. Primary study outcome was freedom from failure proportion at week 16-20 and month 12 visits after randomization. Secondary study outcome was percentage of participants experiencing attentional dysfunction at these visits.

resultsA total of 208 children were enrolled, randomized, and received second therapy. At both week 16-20 visit and month 12 visit, ethosuximide's (63%, 57%) and valproic acid's (65%, 49%) freedom from failure proportions were similar to each other and higher than lamotrigine's (45%, 36%, p = 0.051 and p = 0.062). At both time points, ethosuximide and valproic acid had superior seizure control compared to lamotrigine (p < 0.0001). At both the week 16-20 and month 12 visits, attentional dysfunction was numerically more common with valproic acid than with ethosuximide or lamotrigine. For each medication, second monotherapy freedom from failure proportions demonstrated noninferiority to initial monotherapy freedom from failure proportions.

conclusionsAs second monotherapy, ethosuximide and valproic acid, demonstrated higher freedom from failure proportions and greater efficacy than lamotrigine; valproic acid was associated with more attentional dysfunction. Ethosuximide is the optimal second monotherapy for children with CAE not responding to initial therapy with other medications. CLINICALTRIALSGOV IDENTIFIER: NCT00088452. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for children with CAE experiencing initial treatment failure, second monotherapy with ethosuximide or valproic acid is superior to lamotrigine.

Indexed as

Treatment OutcomeAnticonvulsantsChi-Square DistributionDouble-Blind MethodElectroencephalographyEpilepsy, AbsenceFemaleFollow-Up StudiesHumansMaleSurvival AnalysisAnticonvulsants

Identifiers

PMID27986874
PMCPMC5224720
OpenAlexW2563175025

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.