Paediatrics has been blessed with not one, but two, really important randomised controlled trials on status epilepticus coming to fruition in the last months. PREDICT’s ConSEPT study was reported at #DFTB18 and now the EcLiPSE study, supported by PERUKI, has just released its headline results.
Professor Richard Appleton, Chief Investigator, kindly blogs about the EcLiPSE study having been presented at #EuSEM18
What is, and why ‘EcLiPSE’ is important?
The ‘EcLiPSE’ study (Emergency Treatment with Levetiracetam or Phenytoin in Status Epilepticus in Children) is a large national RCT that compared the effectiveness and safety of i.v levetiracetam (40mg/kg) and i.v phenytoin (20mg/kg) in children aged 6 months to 18 years treated in 30 Emergency Departments (EDs) throughout the UK with benzodiazepine-resistant convulsive status epilepticus (CSE).
CSE is the most common neurological emergency in children and its management is crucial to minimise its potential irreversible neurological and cognitive sequelae.
To date there are no published robust and adequately-powered RCT of any anticonvulsant in the second-line management of CSE. This includes phenytoin despite its many decades’ position in many national CSE-management guidelines, and its well-recognised poor safety-profile, including fatal arrhythmias. Much anecdotal data suggest levetiracetam may be as effective but with a much cleaner safety-profile.
‘EcLiPSE’ provides unique and much-needed evidence for the most appropriate second-line management of CSE in children.
What did ‘EcLiPSE’ show?
Levetiracetam was neither superior nor inferior to phenytoin in terminating CSE (69.7% vs 64.2% respectively), or in its time to terminating the CSE from time of randomisation or infusion-commencement. Levetiracetam showed a trend of being associated with less, and less serious, adverse events and reactions.
What does this mean for the next child that presents in CSE in ED?
This study provides good RCT evidence that levetiracetam or phenytoin could be used as the first choice, second-line anticonvulsant in paediatric CSE. The more rapid infusion time (5 vs 20 minutes respectively) would also suggest it could be given first and phenytoin second, should this be required. However, this decision will be that of the individual ED clinician and individual child’s clinical situation.
Data from two other RCTs (New Zealand + Australia and the US), including a meta-analysis, will be important in deciding whether guidelines and algorithms in the UK, and abroad, should be revised to officially change national clinical practice.
Will this change my practice (Dr. Damian Roland)
It’s a rare occurrence that we have such a rich amount of information available to us at the same time, but we need to be aware that neither EcLiPSE or ConSEPT have been published yet and there is more nuts and bolts data to review than the conference presentations can give us. Having said that it’s clear that change is likely to be on the cards given the ease of being able to deliver levetiracetam. Key questions before units change their guidance will be the ease of use and possible cost effectiveness debate, local experience with untoward events, and the results of a forthcoming meta-analysis. A number of people have asked why EcLiPSE was a superiority, rather than non-inferiority study. This was primarily based on the available anecdotal data for the two drugs and their very different rates of infusion. Clearly, both research networks (PERUKI and PREDICT) have demonstrated large RCTs in paediatric emergency medicine are feasible and it bodes well for the future of deferred consent research for time-critical studies that both EcLiPSE and ConSEPT were completed successfully.
So for the moment, start the debate in your departments, await the publications for journal club and look out for meta-analysis work.