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

2019; Elsevier BV; Volume: 393; Issue: 10186 Linguagem: Inglês

10.1016/s0140-6736(19)30724-x

1474-547X

Mark D Lyttle, Naomi Rainford, Carrol Gamble, Shrouk Messahel, Amy Humphreys, Helen Hickey, Kerry Woolfall, Louise Roper, Joanne Noblet, Elizabeth D. Lee, Sarah Potter, Paul Tate, Anand Iyer, Vicki Evans, Richard Appleton, Matthew Pereira, Susie Hardwick, Shrouk Messahel, Joanne Noblet, Elizabeth D Lee, Rachel Greenwood-Bibby, M S Buchanan, Lucy Lewis, Sharon Hughes, Stuart Hartshorn, Louise Rogers, Juliet Hopkins, Mark D Lyttle, Daphin Fernandez, Sarah Potter, Holly R Lavigne-Smith, Phoebe Moulsdale, Alice Smith, Tracey Bingham, James N. Ross, Natasha Ramsey, Jo Hacking, Niall Mullen, Paul Corrigan, S Prudhoe, Hani Faza, Gisela Robinson, Rachel Sunley, Coral Smith, Vanessa Unsworth, John Criddle, Martin Laque, Alyce B Sheedy, Mark Anderson, Kathryn M. Bell, Kirsty Devine, Alex Scott, Ramesh Kumar, Sonia Armstrong, Emer Sutherland, Fleur Cantle, Sinead Helyer, Paul Riozzi, Hannah Cotton, Alice Downes, Helen Mollard, Damian Roland, Felix Hay, Christopher M. Gough, Sonya Finucane, Catherine Bevan, Rebecca Ramsay, Emily Walton, Julie‐Ann Maney, Elizabeth Dalzell, Muriel Millar, R J Howells, Andy Appelboam, Daisy Mackle, J. G. Small, Ashleigh Neil, V. Choudhery, Stewart MacLeod, J Browning, Thomas J. O’Neill, Julia Grahamslaw, Ami Parikh, Imogen Skene, Rhys Thomas, Katherine Potier de la Morandiere, Jill L Wilson, Donna Danziger, Derek Burke, Shammi Ramlakhan, Jayne Evans, Julie Morcombe, Stuart Gormley, Jason M Barling, Katrina Cathie, Jane Bayreuther, Ruth Ensom, Yasser Iqbal, Sarah Rounding, Joanne Mulligan, Claire L. Bell, Shona McLellan, Shona Leighton, T Sajjanhar, Moffat Nyirenda, Laura Crome, Neil Williamson, Anastasia Alcock, Sara Edwards, Jeffrey R. Morgan, Colin Powell, Chaniyil A Ramesh, Solomon Kamal-Uddin, Mike Linney, Katia Vamvakiti, Sharon Floyd, Gill Hobden,

Metabolism and Genetic Disorders

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.National Institute for Health Research Health Technology Assessment programme.