Abstracts

Rationale: There are a small number of marketed intravenous antiepileptic drugs, of which only a few have been studied for status epilepticus (SE). Performing human studies in the current regulatory environment is almost impossible without some evidence that the new agent may be effective. Epilepsy and SE occur naturally in dogs with prevalence, presentation, and percentage of refractory cases similar to human epilepsy. Methods: Informed consent was obtained from the owners of dogs with SE or acute repetitive seizures. Dogs who failed initial benzodiazepine (BZD) treatment were randomized to an IV infusion of 30 mg/kg (n=5) or 60mg/kg (n=4) of the human formulation of levetiracetam (LEV) or to saline placebo. If seizures continued for more than 5 minutes, additional IV BZD or IV phenobarbital was administered per the standard of care for veterinary patients. Dogs were observed for 24 hours in a veterinary ICU and LEV plasma levels were measured. Results: Nineteen dogs were randomized (9 to LEV and 10 to placebo). In the LEV group 55.6% had no more seizures compared to 10.0% in the placebo group (p=0.0573). In-hospital mortality was 2/9 in the LEV group vs. 4/10 in the placebo group. There were no statistically significant differences in adverse events between the groups. Conclusions: This proof of concept study provides the first evidence that LEV is safe and effective in canine SE/acute repetitive seizures. Further, naturally occurring canine SE may provide a proof of principle platform for translating drug studies in rodent models to human SE trials.