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Lancet. 2019 May 25;393(10186):2125-2134. doi: 10.1016/S0140-6736(19)30724-X. Epub 2019 Apr 17.

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial.

Author information

1
Emergency Department, Bristol Royal Hospital for Children, Bristol, UK; Faculty of Health and Applied Sciences, University of the West of England, Bristol, UK.
2
Clinical Trials Research Centre, University of Liverpool, Liverpool, UK; Institute of Child Health, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
3
Department of Biostatistics, University of Liverpool, Liverpool, UK; Clinical Trials Research Centre, University of Liverpool, Liverpool, UK; Institute of Child Health, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
4
Emergency Department, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
5
Institute of Population Health Sciences, University of Liverpool, Liverpool, UK.
6
Emergency Department, Bristol Royal Hospital for Children, Bristol, UK.
7
Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
8
Wrexham, Clwyd, UK.
9
Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK. Electronic address: richardappleton55@hotmail.co.uk.

Abstract

BACKGROUND:

Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.

METHODS:

This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.

FINDINGS:

Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91-1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]).

INTERPRETATION:

Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus.

FUNDING:

National Institute for Health Research Health Technology Assessment programme.

PMID:
31005385
PMCID:
PMC6551349
DOI:
10.1016/S0140-6736(19)30724-X
[Indexed for MEDLINE]
Free PMC Article

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