Two RCTs: levetiracetam is not superior to phenytoin to treat status epilepticus but is easier to use and may be safer

Référence

Lyttle MD, Rainford NEA, Gamble C, et al, for the Paediatric Emergency Research in the United Kingdom & Ireland (PERUKI) collaborative. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet 2019;393(10186):2125-2134.

Sommaire

Benzodiazepines are first-line treatment for children with status epilepticus, but they only work 40% to 60% of the time. Phenytoin, the currently recommended second-line agent, requires slow administration and can cause hypotension and cardiac arrhythmias. The authors of the 2 studies (one study in the United Kingdom, the other in Australia and New Zealand) used comparable methods: open-label trials of children who presented to emergency departments in status epilepticus needing second-line treatment. The children received either levetiracetam (40 mg/kg over 5 minutes; n [for the 2 studies] = 271) or phenytoin (20 mg/kg over 20 minutes; n = 248). In the EcLiPSE trial, the main outcome was the time to cessation of all seizure activity (similar mean time with levetiracetam and phenytoin: 35 and 45 minutes, respectively), while in ConSEPT the main outcome was whether seizure activity stopped 5 minutes after completing the infusion (again, similar: 60% vs 50%, respectively). In EcLiPSE, one third of patients in each group required an additional anticonvulsant and approximately 20% required rapid sequence induction to halt the seizures. In ConSEPT, however, approximately one quarter of the children in each group required rapid sequence induction. In each study, one child died; each had received phenytoin. In the EcLiPSE trial, one child treated with phenytoin developed life-threatening hypotension, increased focal seizures, and decreased consciousness. ConSEPT reported no other serious events, but it will take a larger study to confidently say that one drug is safer than the other.