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Emergency treatment with levetiracetam or phenytoin in status epilepticus in children—the EcLiPSE study: study protocol for a randomised controlled trial
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,...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477100/ https://www.ncbi.nlm.nih.gov/pubmed/28629473 http://dx.doi.org/10.1186/s13063-017-2010-8 |
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author | Lyttle, Mark D. Gamble, Carrol Messahel, Shrouk Hickey, Helen Iyer, Anand Woolfall, Kerry Humphreys, Amy Bacon, Naomi E. A. Roper, Louise Babl, Franz E. Dalziel, Stuart R. Ryan, Mary Appleton, Richard E. |
author_facet | Lyttle, Mark D. Gamble, Carrol Messahel, Shrouk Hickey, Helen Iyer, Anand Woolfall, Kerry Humphreys, Amy Bacon, Naomi E. A. Roper, Louise Babl, Franz E. Dalziel, Stuart R. Ryan, Mary Appleton, Richard E. |
author_sort | Lyttle, Mark D. |
collection | PubMed |
description | 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 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-017-2010-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5477100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-54771002017-06-22 Emergency treatment with levetiracetam or phenytoin in status epilepticus in children—the EcLiPSE study: study protocol for a randomised controlled trial Lyttle, Mark D. Gamble, Carrol Messahel, Shrouk Hickey, Helen Iyer, Anand Woolfall, Kerry Humphreys, Amy Bacon, Naomi E. A. Roper, Louise Babl, Franz E. Dalziel, Stuart R. Ryan, Mary Appleton, Richard E. Trials Study Protocol 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 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-017-2010-8) contains supplementary material, which is available to authorized users. BioMed Central 2017-06-19 /pmc/articles/PMC5477100/ /pubmed/28629473 http://dx.doi.org/10.1186/s13063-017-2010-8 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Study Protocol Lyttle, Mark D. Gamble, Carrol Messahel, Shrouk Hickey, Helen Iyer, Anand Woolfall, Kerry Humphreys, Amy Bacon, Naomi E. A. Roper, Louise Babl, Franz E. Dalziel, Stuart R. Ryan, Mary Appleton, Richard E. Emergency treatment with levetiracetam or phenytoin in status epilepticus in children—the EcLiPSE study: study protocol for a randomised controlled trial |
title | Emergency treatment with levetiracetam or phenytoin in status epilepticus in children—the EcLiPSE study: study protocol for a randomised controlled trial |
title_full | Emergency treatment with levetiracetam or phenytoin in status epilepticus in children—the EcLiPSE study: study protocol for a randomised controlled trial |
title_fullStr | Emergency treatment with levetiracetam or phenytoin in status epilepticus in children—the EcLiPSE study: study protocol for a randomised controlled trial |
title_full_unstemmed | Emergency treatment with levetiracetam or phenytoin in status epilepticus in children—the EcLiPSE study: study protocol for a randomised controlled trial |
title_short | Emergency treatment with levetiracetam or phenytoin in status epilepticus in children—the EcLiPSE study: study protocol for a randomised controlled trial |
title_sort | emergency treatment with levetiracetam or phenytoin in status epilepticus in children—the eclipse study: study protocol for a randomised controlled trial |
topic | Study Protocol |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477100/ https://www.ncbi.nlm.nih.gov/pubmed/28629473 http://dx.doi.org/10.1186/s13063-017-2010-8 |
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