The researchers suggest that despite not detecting a significant difference between phenytoin and levetiracetam for any outcome, including time to seizure cessation, these results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, indicate it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus.
This is one of two studies in the Lancet looking at whether levetiracetam was superior to phenytoin in children with status epilepticus. The other study (ConSEPT), conducted in Australia and New Zealand, also found that levetiracetam is not superior to phenytoin for 2nd line management (clinical cessation of seizure activity 5 min after completion of infusion occurred in 60% on phenytoin and 50% on levetiracetam; p=0.16).
According to a commentary, the consistency of the findings in these contemporaneous, but independent trials is notable. The commentators themselves are conducting a third trial in the USA, also comparing levetiracetam and phenytoin, as well as valproate, in children and adults with continued generalised convulsive status epilepticus after benzodiazepines.
They note that the strengths of both trials are their clinical relevance- despite the challenges of conducting high-quality clinical trials in the fast-paced, sometimes chaotic, emergency settings, ConSEPT and EcLiPSE effectively integrated the research into the routine clinical resuscitation workflow of these acutely ill patients, making the results relevant and credible. They add that these results provide confidence that slightly more than half of children with convulsive status epilepticus will clinically resolve after treatment with either of these second-line anticonvulsants, but whether a 50% clinical response rate is strong or weak remains a controversy, but certainly allows for improvement. They discuss weaknesses inherent in both of these trials in that the intervention was delivered without masking, and the primary outcome was determined clinically by the treating physicians, because determining exactly when a child's seizures have stopped can be subjective, and before stopping, convulsion can stutter or pitter out rather than cease abruptly. Furthermore, subjectivity not only complicates clinical determination of cessation of seizures but also complicates subsequent clinical decision making about when to use additional rescue doses of anticonvulsants and when to proceed to endotracheal intubation. They postulate that similar clinical outcomes with both drugs in these trials might indicate a similar pharmacological effect on seizures but alternatively might show that clinical factors other than the drugs might be driving the clinical outcome more strongly. If so, research to improve clinical outcomes might have to assess more than just the choice of medication.