Levetiracetam and Midazolam vs Midazolam Alone for First-Line Treatment of Children With Generalized Convulsive Status Epilepticus (Lev-Mid Study): A Randomized Controlled Trial

Background Benzodiazepines are the first-line anti-seizure medication (ASM) for generalized convulsive status epilepticus (GCSE), but they fail to end seizures in a third of cases. Combining benzodiazepines with another ASM that acts by a different pathway could be a potential strategy for rapid control of GCSE. Objectives To evaluate the efficacy of adding levetiracetam to midazolam in the initial treatment of pediatric GCSE. Design Double-blind randomized controlled trial. Setting Pediatric emergency room at Sohag University Hospital between June, 2021 and August, 2022. Participants Children aged between 1 month and 16 years with GCSE lasting more than 5 min. Interventions Intravenous levetiracetam (60 mg/kg over 5 min) and midazolam (Lev-Mid group) or placebo and midazolam (Pla-Mid group) as first-line anticonvulsive therapy. Outcome measures Primary: cessation of clinical seizures at 20-min study time point. Secondary: cessation of clinical seizures at 40-min study time point, need for a second midazolam dose, seizure control at 24-hr, need for intubation, and adverse effects. Results Cessation of clinical seizures at 20-min occurred in 55 children (76%) in Lev-Mid group compared with 50 (69%) in the Pla-Mid group [RR (95% CI) 1.1 (0.9–1.34); P =0.35]. No significant difference was found between the two groups regarding the need for a second midazolam dose [44.4% vs 55.6%; RR (95% CI) 0.8 (0.58–1.11); P =0.18] as well as cessation of clinical seizures at 40-min [96% vs 92%; RR (95% CI)1.05 (0.96–1.14); P=0.49] and seizure control at 24-hr [85% vs 76%; RR (95% CI) 1.12 (0.94–1.3); P =0.21]. Intubation was required for three patients in the Lev-Mid group and six patients in the Pla-Mid group [RR (95%CI) 0.5 (0.13–1.92); P =0.49]. No other adverse effects or mortality were observed during the 24-hour study timeframe. Conclusion Combined levetiracetam and midazolam for initial management of pediatric GCSE presents no significant advantage over midazolam alone in cessation of clinical seizures at 20-min.