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Vigabatrin withdrawal randomized study in children
1Neuropediatric Department, INSERM U29, University René Descartes, Hospital Saint Vincent de Paul, Paris, France.
Insights
This study demonstrates the feasibility of a novel randomized withdrawal design for evaluating vigabatrin (VGB) in children with refractory epilepsy. The design confirmed VGB
Area of Science:
- Pediatric Neurology
- Clinical Pharmacology
Background:
- Controlled trials for new antiepileptic drugs in children are challenging.
- Randomized withdrawal designs offer a method to compare drugs against placebo without delaying treatment.
Purpose of the Study:
- To assess the efficacy and feasibility of a randomized withdrawal design for vigabatrin (VGB) in pediatric epilepsy.
- To provide the first controlled study of VGB in children using this novel trial methodology.
Main Methods:
- A randomized withdrawal design was employed in 28 children (1.5-18.5 years) with refractory epilepsy partially responding to VGB.
- Patients were randomized to continue VGB or receive a placebo for 2 months, with seizure frequency compared to a pre-randomization period.
Main Results:
- Significantly more patients remained in the study receiving VGB (93%) compared to placebo (46%) (P < 0.01).
- Seizure frequency was significantly lower in the VGB group than the placebo group (P < 0.05).
- No cases of status epilepticus occurred during VGB withdrawal.
Conclusions:
- The randomized withdrawal design is feasible and effective for studying antiepileptic drugs in children.
- This study provides the first controlled evidence of vigabatrin's efficacy in pediatric epilepsy using this design.
- The methodology could be valuable for future clinical trials in childhood epilepsy.
Abstract:
Controlled studies with new antiepileptic drugs are problematic and limited in children. Withdrawal randomization versus placebo in responders previously recognized in an open phase is a new design reported in adults which allows comparison to placebo without delaying the administration of the active compound. We applied such a design in refractory epileptic children in order to study vigabatrin (VGB) in children. Twenty-eight patients aged 1.5-18.5 years and having partially responded to VGB, prescribed in an open study for refractory epilepsy, were included. Patients were randomized to VGB (continued) or placebo (VGB blindy stopped in 3 weeks) for 2 months and seizure frequency was compared to the prerandomization period. More than 50% increase in seizure frequency induced drop-out. Fifteen patients received VGB, 13 others placebo, with the same clinical characteristics in both groups. The patients remaining in the study (primary efficacy endpoint) were more numerous on VGB (93%) than on placebo (46%) (P < 0.01) and seizure frequency (secondary endpoint) was lower on VGB than placebo (P < 0.05). The same results were observed in a subgroup of partial epilepsies. No status epilepticus was observed when withdrawing VGB and all patients returned to baseline status by reintroducing VGB. Such a randomized withdrawal design is therefore feasible in epileptic children. It provides the first VGB controlled study in this age range and demonstrates efficacy. It could be useful for future designs of drug trials in childhood epilepsy.