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Published in: Trials 1/2017

Open Access 01-12-2017 | Study protocol

Emergency treatment with levetiracetam or phenytoin in status epilepticus in children—the EcLiPSE study: study protocol for a randomised controlled trial

Authors: Mark D. Lyttle, Carrol Gamble, Shrouk Messahel, Helen Hickey, Anand Iyer, Kerry Woolfall, Amy Humphreys, Naomi E. A. Bacon, Louise Roper, Franz E. Babl, Stuart R. Dalziel, Mary Ryan, Richard E. Appleton, supported by Paediatric Emergency Research in the United Kingdom & Ireland (PERUKI)

Published in: Trials | Issue 1/2017

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Abstract

Background

Convulsive status epilepticus (CSE) is the most common life-threatening neurological emergency in childhood. These children are also at risk of significant morbidity, with acute and chronic impact on the family and the health and social care systems. The current recommended first-choice, second-line treatment in children aged 6 months and above is intravenous phenytoin (fosphenytoin in the USA), although there is a lack of evidence for its use and it is associated with significant side effects. Emerging evidence suggests that intravenous levetiracetam may be effective as a second-line agent for CSE, and fewer adverse effects have been described. This trial therefore aims to determine whether intravenous phenytoin or levetiracetam is more effective, and safer, in treating childhood CSE.

Methods/design

This is a phase IV, multi-centre, parallel group, randomised controlled, open-label trial. Following treatment for CSE with first-line treatment, children with ongoing seizures are randomised to receive either phenytoin (20 mg/kg, maximum 2 g) or levetiracetam (40 mg/kg, maximum 2.5 g) intravenously. The primary outcome measure is the cessation of all visible signs of CSE as determined by the treating clinician. Secondary outcome measures include the need for further anti-seizure medications or rapid sequence induction for ongoing CSE, admission to critical care areas, and serious adverse reactions. Patients are recruited without prior consent, with deferred consent sought at an appropriate time for the family. The primary analysis will be by intention-to-treat. The primary outcome is a time to event outcome and a sample size of 140 participants in each group will have 80% power to detect an increase in CSE cessation rates from 60% to 75%. Our total sample size of 308 randomised and treated participants will allow for 10% loss to follow-up.

Discussion

This clinical trial will determine whether phenytoin or levetiracetam is more effective as an intravenous second-line agent for CSE, and provide evidence for management recommendations. In addition, this trial will also provide data on which of these therapies is safer in this setting.

Trial registration

ISRCTN identifier, ISRCTN22567894. Registered on 27 August 2015
EudraCT identifier, 2014-002188-13. Registered on 21 May 2014
NIHR HTA Grant: 12/​127/​134
Appendix
Available only for authorised users
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Metadata
Title
Emergency treatment with levetiracetam or phenytoin in status epilepticus in children—the EcLiPSE study: study protocol for a randomised controlled trial
Authors
Mark D. Lyttle
Carrol Gamble
Shrouk Messahel
Helen Hickey
Anand Iyer
Kerry Woolfall
Amy Humphreys
Naomi E. A. Bacon
Louise Roper
Franz E. Babl
Stuart R. Dalziel
Mary Ryan
Richard E. Appleton
supported by Paediatric Emergency Research in the United Kingdom & Ireland (PERUKI)
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Trials / Issue 1/2017
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-017-2010-8

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