Emergency treatment with levetiracetam or phenytoin in status epilepticus in children—the EcLiPSE study: study protocol for a randomised controlled trial

Abstract

BackgroundConvulsive 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/designThis 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.DiscussionThis 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 registrationISRCTN identifier, ISRCTN22567894. Registered on 27 August 2015EudraCT identifier, 2014-002188-13. Registered on 21 May 2014NIHR HTA Grant: 12/127/134 Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2010-8) contains supplementary material, which is available to authorized users.

Parents’ and clinicians’ views on conducting paediatric diagnostic test accuracy studies without prior informed consent: qualitative insight from the Petechiae in Children study (PiC)

“…Although some parents asked clinicians why consent was needed for the PiC study, when presented with a hypothetical alternative approach, parents favoured a full RWPC discussion with a member of the research team over provision of written materials and the opportunity to opt out from having their child’s data included in the study. As consistently shown in previous studies exploring trial recruitment processes, parents valued conversations with clinicians above written information materials 14–20. Parents stated they would not have opted out of the PiC study.…”

“…We used previous research14–20 to develop interview topic guides (online supplementary file 1), which contained open-ended questions and prompts to explore views and experiences of the PiC study, including use of an RWPC approach. TW (male paediatrician) received qualitative research training from KW (female social scientist).…”

“…Studies investigating the diagnostic test accuracy (DTA) of rapid tests for SBI require research without prior consent (RWPC; also known as deferred consent) as the diagnosis and treatment of potentially life-threatening infections is time critical,12 13 and by definition, such studies are focused on obtaining very rapid test results. RWPC has successfully been used in paediatric emergency interventional studies, but there is a lack of knowledge about parent and clinician perspectives on the acceptability of RWPC in DTA studies 14–20Table 1 compares different models of consent including RWPC, prospective informed consent and opt-out consent.…”

The “Petechiae in children” (PiC) study: evaluating potential clinical decision rules for the management of feverish children with non-blanching rashes, including the role of point of care testing for Procalcitonin & Neisseria meningitidis DNA – a study protocol

“…In the majority of cases this will take place on a ward or in the ED. Consent will only be sought once the child is stable and following consultation with the clinical team caring for the child in line with best practice recommendations [ 15 – 17 ].…”

Status epilepticus im Kindes- und Jugendalter – ein oft unterschätztes Notfallereignis

“…Derzeit laufen umfangreiche Studien (ConSEPT: Convulsive Status Epilepticus Paediatric Trial, EcLiPSE, ESETT: Established Status Epilepticus Treatment Trail), die an insgesamt 1300 pädiatrischen Patienten Phenytoin, Levetiracetam und Valproat vergleichen. Erste Ergebnisse sind Ende 2019 zu erwarten [3,18].…”