JAMA Neurol

IMPORTANCEFenfluramine treatment may reduce monthly convulsive seizure frequency in patients with Dravet syndrome who have poor seizure control with their current stiripentol-containing antiepileptic drug regimens.OBJECTIVETo determine whether fenfluramine reduced monthly convulsive seizure frequency relative to placebo in patients with Dravet syndrome who were taking stiripentol-inclusive regimens.DESIGN, SETTING, AND PARTICIPANTSThis double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted in multiple centers. Eligible patients were children aged 2 to 18 years with a confirmed clinical diagnosis of Dravet syndrome who were receiving stable, stiripentol-inclusive antiepileptic drug regimens.INTERVENTIONSPatients with 6 or more convulsive seizures during the 6-week baseline period were randomly assigned to receive fenfluramine, 0.4 mg/kg/d (maximum, 17 mg/d), or a placebo. After titration (3 weeks), patients' assigned dosages were maintained for 12 additional weeks. Caregivers recorded seizures via a daily electronic diary.MAIN OUTCOMES AND MEASURESThe primary efficacy end point was the change in mean monthly convulsive seizure frequency between fenfluramine and placebo during the combined titration and maintenance periods relative to baseline.RESULTSA total of 115 eligible patients were identified; of these, 87 patients (mean [SD], age 9.1 [4.8] years; 50 male patients [57%]; mean baseline frequency of seizures, approximately 25 convulsive seizures per month) were enrolled and randomized to fenfluramine, 0.4 mg/kg/d (n = 43) or placebo (n = 44). Patients treated with fenfluramine achieved a 54.0% (95% CI, 35.6%-67.2%; P