NEOLEV3: high dose levetiracetam in NZ neonates with seizures

Neonatal seizures affect 1/300 infants, about 200/ year in NZ. Survivors have high rates (40-60%) of permanent disabilities (cerebral palsy, global developmental delay, epilepsy). Improved seizures treatments could improve long-term neurodevelopmental outcomes.

The NEOLEV2 trial showed better seizure control with phenobarbital (PHB) than Levetiracetam (LEV), however PHB caused more side effects (respiratory suppression, hypotension, sedation). There are also concerns regarding long-term neurocognitive side effects of PHB.

NEOLEV3 is an FDA-funded dose escalation and safety study investigating whether higher doses of LEV have greater efficacy, since LEV is less toxic and well-tolerated. Infants with mild-moderate seizure burden, where it is less clear that benefits of seizure elimination outweigh risks of PHB, are treated first with LEV. In study Phase 1, the LEV dose is escalated to 90mg/kg. In Phase 2,a 120mg/kg dose is tested. In Phase 3 a 150mg/kg dose will be tested.

NEOLEV3 has been recruiting for two years, with US and NZ NICU study sites. Phase 1 is complete and Phase 2 has started. However no participants have been treated at US sites. In Auckland 76 patients have been recruited and monitored, and 33 have been treated for seizures, with no safety concerns. Wellington NICU will join the study soon. Given NZ recruitment success, and the uncertainty and difficulty of securing FDA funds to cover extra costs, we aim to secure funding to extend the study to Waikato NICU. Waikato have many eligible babies, who would benefit from the intensive EEG monitoring, and contribute to successful trial completion.