- First-line phenobarbital is superior to levetiracetam for achieving sustained freedom from neonatal seizures.
Why this matters
- Phenobarbital has limited efficacy and questionable safety for developing brains.
- Trials among neonates in the hypothermia era are limited.
- Seizure freedom for 24 hours on continuous video EEG monitoring was less common with levetiracetam vs phenobarbital:
- Rate: 28% vs 80% (P<.001>
- Relative risk: 0.35 (95% CI, 0.22-0.56).
- Any grade 4/5 adverse event, serious adverse event: 12% vs 6% (P=.48).
- Hypotension: 17% vs 5% (P=.05).
- Respiratory abnormality: 26% vs 13% (P=.12).
- Vasopressor support: 31% vs 16% (P=.09).
- US multicenter phase 2b randomized controlled trial among 106 term neonates with any-cause seizures (54% because of hypoxic-ischemic encephalopathy; NEOLEV2 trial).
- Randomization: 60:40 to levetiracetam vs phenobarbital (control) at first confirmation of seizure.
- Main outcome: complete seizure freedom for 24 hours on independent review of EEGs by 2 neurophysiologists.
- Funding: FDA Orphan Products Division.
- 23 infants excluded from modified intention-to-treat population.
- Seizures possibly resolved spontaneously in some cases.
- Use of short-term endpoint.