Efficacy and Safety of Levetiracetam Versus Fosphenytoin in Adult Convulsive Status Epilepticus: An Open-Label Randomized Controlled Trial

BackgroundConvulsive status epilepticus is a time-critical neurological emergency, and the choice of second-line intravenous antiseizure medication in resource-limited hospitals rests on habit rather than on local evidence.We compared intravenous levetiracetam with intravenous fosphenytoin in adults whose convulsive status epilepticus persisted after intravenous diazepam. MethodsThis single-center, open-label, parallel-group randomized controlled trial was conducted in the Department of Neurology of Dhaka Medical College Hospital, Dhaka, Bangladesh, from May 2023 to August 2024.A total of 62 adults aged 18 years or older who continued to convulse 15 minutes after intravenous diazepam 10 mg were allocated in a 1:1 ratio by block randomization to fosphenytoin 20 mg per kg phenytoin sodium equivalent or levetiracetam 60 mg per kg.The primary efficacy endpoint, on which the sample size was based, was cessation of clinically apparent seizures within 30 minutes of starting the trial drug without any additional anticonvulsant.Sustained seizure control to 24 hours and treatment emergent adverse events at 24 hours, which together formed the registered primary outcome, were also assessed.Secondary outcomes included time to seizure termination, recurrence within 24 hours, treatment emergent adverse events, intensive care admission, endotracheal intubation, length of hospital stay, all-cause in-hospital mortality, modified Rankin Scale score at seven days or discharge, and total drug cost. ResultsSeizure cessation within 30 minutes was achieved in 16 of 31 patients (51.6%) given fosphenytoin and 20 of 31 patients (64.5%) given levetiracetam, an absolute difference of 12.9% (95% CI: -11.5 to 37.3; p = 0.303).Seizure control sustained to 24 hours, the efficacy component of the registered primary outcome, was achieved in 38.7% and 48.4%, respectively (p = 0.442).Among responders, convulsions stopped at a median of 13.5 minutes with fosphenytoin and 11.0 minutes with levetiracetam (p = 0.034).Recurrence within 24 hours was similar (12.9% with fosphenytoin and 16.1% with levetiracetam; p = 1.000), but the mean seizurefree interval before recurrence was longer with levetiracetam (229.2 versus 92.5 minutes; p = 0.045).Treatment emergent adverse events at 24 hours were less frequent with levetiracetam than with fosphenytoin (38.7% versus 71.0%; p = 0.011), with lower rates of sedation, itching, and rash.Intensive care admission, intubation within 24 hours, length of hospital stay, in-hospital mortality (6.5% with fosphenytoin and 9.7% with levetiracetam; p = 1.000), modified Rankin Scale distribution at seven days or discharge, and total drug cost (median 1272 taka with fosphenytoin and 1100 taka with levetiracetam; p = 0.137) were comparable between the groups.The same molecule was continued as oral maintenance therapy in 78.6% of levetiracetam recipients compared with 13.8% of fosphenytoin recipients (p < 0.001). ConclusionsNo statistically significant difference was found between levetiracetam and fosphenytoin in stopping benzodiazepine refractory convulsive status epilepticus in adults, although this small open-label trial cannot establish equivalence.Levetiracetam was better tolerated at 24 hours, cost no more, and simplified the transition to oral therapy, which makes it a reasonable second-line option for hospitals with limited monitoring and critical care capacity while larger blinded trials are awaited.