A multicentre, randomized prospective trial comparing add-on therapy with alternative monotherapy in patients with partial seizures refractory to initial treatment

A prospective multicentre randomized trial will be performed to evaluate the comparative efficacy and tolerability of add-on therapy vs alternative monotherapy in 440 patients with partial seizures (with or without secondary generalization) refractory to initial monotherapy. A group of patients who received sequential monotherapies will also be evaluated. Patients with symptomatic or cryptogenic partial epilepsy who failed to achieve freedom from seizures despite adequate monotherapy will be randomized to two groups. One group will be crossed-over to an alternative antiepileptic drug over a period not exceeding 4 months while in the other group the alternative drug will be added on over the same time frame. Seizure frequency and the occurrence of adverse effects will be assessed over a 1-year follow-up period in order to assess potential differences between the two groups. The primary outcome parameter will be represented by retention time on the allocated treatment policy. Other outcome parameters will include: dissatisfaction time with the allocated treatment policy; time to first seizure after achievement of the target dosage(s); proportion of patients achieving at least a 50% reduction in seizure frequency during the last 3 months of follow-up; proportion of patients becoming seizure fre; proportion of patients achieving 6-month remission, seizure number at different study periods compared with seizure number at baseline, number of treatment failures, and the proportion of patients with adverse effects.