Abstract found on PubMed
Objective: To test the hypothesis that early vigabatrin treatment in Tuberous Sclerosis Complex (TSC) infants improves neurocognitive outcome at 24 months of age.
Methods: Phase IIb multicenter randomized double-blind placebo-controlled trial of vigabatrin at first epileptiform EEG vs. vigabatrin at seizure onset in infants with TSC.
Primary outcome: Bayley-III cognitive assessment score at 24 months.
Secondary outcomes: prevalence of drug resistant epilepsy, additional developmental outcomes, and safety of vigabatrin.
Results: Of eighty-four infants enrolled, 12 were screen failures, four went straight to open label vigabatrin, and 12 were not randomized (normal EEG throughout). 56 were randomized to early vigabatrin (n=29) or placebo (n=27). 19 of 27 in the placebo arm transitioned to open label vigabatrin with a median delay of 44 days after randomization. Bayley-III cognitive composite scores at 24 months were similar for participants randomized to vigabatrin or placebo. Additionally, no significant differences were found between groups in overall epilepsy incidence and drug resistant epilepsy at 24 months, time to first seizure after randomization, and secondary developmental outcomes. Incidence of infantile spasms was lower and time to spasms after randomization was later in the vigabatrin group. Adverse events were similar across groups.
Interpretation: Preventative treatment with vigabatrin based on EEG epileptiform activity prior to seizure onset does not improve neurocognitive outcome at 24 months in TSC children; nor delay onset or lower the incidence of focal seizures and drug resistant epilepsy at 24 months. Preventative vigabatrin was associated with later time to onset and lower incidence of infantile spasms.