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

Crome, Laura; Nyirenda, Maggie; Sajjanhar, Tina; Leighton, Shona; McLellan, Shona; Bell, Claire; Mulligan, Joanne; Rounding, Sarah; Iqbal, Yasser; Ensom, Ruth; Bayreuther, Jane; Cathie, Katrina; Barling, Jason M.; Gormley, Stuart; Morcombe, Julie; Evans, Jayne; Ramlakhan, Shammi; Burke, Derek; Danziger, Donna; Wilson, Jill L.; Potier de la Morandiere, Katherine; Thomas, Rhys; Skene, Imogen; Parikh, Ami; Grahamslaw, Julia; O'Neill, Thomas; Browning, Jen; MacLeod, Stewart; Choudhery, Vince; Neil, Ashleigh; Small, Jennie; Mackle, Daisy; Appelboam, Andy; Howells, Rachel J.; Millar, Muriel; Dalzell, Elizabeth; Maney, Julie Ann; Walton, Emily; Ramsay, Rebecca; Bevan, Catherine; Finucane, Sonya; Gough, Christopher; Hay, Felix; Roland, Damian; Mollard, Helen; Downes, Alice J.; Cotton, Hannah; Riozzi, Paul; Helyer, Sinead; Cantle, Fleur; Sutherland, Emer; Armstrong, Sonia; Kumar, Ramesh; Scott, Alex; Devine, Kirsty; Bell, Kathryn; Anderson, Mark; Sheedy, Alyce B.; Laque, Martin; Criddle, John;...


Laura Crome

Maggie Nyirenda

Tina Sajjanhar

Shona Leighton

Shona McLellan

Claire Bell

Joanne Mulligan

Sarah Rounding

Yasser Iqbal

Ruth Ensom

Jane Bayreuther

Katrina Cathie

Jason M. Barling

Stuart Gormley

Julie Morcombe

Jayne Evans

Shammi Ramlakhan

Derek Burke

Donna Danziger

Jill L. Wilson

Katherine Potier de la Morandiere

Rhys Thomas

Imogen Skene

Ami Parikh

Julia Grahamslaw

Thomas O'Neill

Jen Browning

Stewart MacLeod

Vince Choudhery

Ashleigh Neil

Jennie Small

Daisy Mackle

Andy Appelboam

Rachel J. Howells

Muriel Millar

Elizabeth Dalzell

Julie Ann Maney

Emily Walton

Rebecca Ramsay

Catherine Bevan

Sonya Finucane

Christopher Gough

Felix Hay

Damian Roland

Helen Mollard

Alice J. Downes

Hannah Cotton

Paul Riozzi

Sinead Helyer

Fleur Cantle

Emer Sutherland

Sonia Armstrong

Ramesh Kumar

Alex Scott

Kirsty Devine

Kathryn Bell

Mark Anderson

Alyce B. Sheedy

Martin Laque

John Criddle

Vanessa Unsworth

Coral J. Smith

Rachel C. Sunley

Gisela Robinson

Hani Faza

Sarah Prudhoe

Paul P. Corrigan

Niall Mullen

Jo Hacking

Natasha Ramsey

James Ross

Tracey Bingham

Alice Smith

Phoebe Moulsdale

Holly R. Lavigne-Smith

Daphin Fernandez

Juliet Hopkins

Louise Rogers

Stuart Hartshorn

Sharon Hughes

Lucy Lewis

Mark Buchanan

Rachel Greenwood-Bibby

Susie Hardwick

Matthew Pereira

Richard E. Appleton

Vicki Evans

Anand Iyer

Paul Tate

Sarah Potter

Elizabeth D. Lee

Joanne Noblet

Louise Roper

Kerry Woolfall

Helen Hickey

Amy Humphreys

Shrouk Messahel

Carrol Gamble

Naomi E.A. Rainford


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.

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.

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]).

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.


Crome, L., Nyirenda, M., Sajjanhar, T., Leighton, S., McLellan, S., Bell, C., …Lyttle, M. D. (2019). Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet, 393(10186), 2125-2134.

Journal Article Type Article
Acceptance Date Mar 14, 2019
Online Publication Date Apr 17, 2019
Publication Date May 25, 2019
Deposit Date Apr 29, 2019
Publicly Available Date Apr 29, 2019
Journal The Lancet
Print ISSN 01406736
Electronic ISSN 1474-547X
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 393
Issue 10186
Pages 2125-2134
Keywords levetiracetam, phenytoin, convulsive status epilepticus, epilepsy, paediatric
Public URL
Publisher URL


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