Stiripentol in childhood partial epilepsy: randomized placebo-controlled trial with enrichment and withdrawal design.
Stiripentol, a new antiepileptic drug inhibiting cytochrome P450-enzymes, suggested some efficacy when combined with carbamazepine in an open trial in refractory partial epilepsy of childhood. Our objective was to test these results in a placebo-controlled trial. To limit the number of patients included, we used an enrichment and withdrawal design. Among the 67 children entered in a 4-month open add-on stiripentol study following a 1-month single-blind placebo baseline, the 32 responders were randomized for 2 months either to continue stiripentol (n = 17) or to withdraw to placebo (n = 15). If seizures increased by at least 50% after randomization compared with baseline, the patients dropped out (primary end point): there were six patients on stiripentol and eight patients on placebo (not significant). However, a decrease in seizure frequency compared with baseline (secondary end point) was greater on stiripentol (-75%) than on placebo (-22%) (P < .025). Twelve patients experienced at least one adverse event on stiripentol (71%) compared with four patients on placebo (27%); none were reported as severe. The combination of stiripentol and carbamazepine proved to reduce seizure frequency in children with refractory partial epilepsy, although it failed to show a significant impact according to the escape criteria selected as the primary end point in the present study, for ethical reasons.
Chiron
Catherine
C
INSERM U663, Service de Neurologie et Metabolisme, Hôpital Necker-Enfants Malades, 149 Rue de Sevres, F-75015 Paris, France. catherine.chiron@nck.aphp.fr
Tonnelier
Sylvie
S
Rey
Elisabeth
E
Brunet
Marie-Lucie
ML
Tran
Agnes
A
d'Athis
Philippe
P
Vincent
Jean
J
Dulac
Olivier
O
Pons
Gerard
G
D000293:Adolescent; D000927:Anticonvulsants / Q000008:administration & dosage*; D002220:Carbamazepine / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D004148:Dioxolanes / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D016896:Treatment Outcome; D028761:Withholding Treatment
D000927:Anticonvulsants; D004148:Dioxolanes; D002220:Carbamazepine; C021092:stiripentol