Neonatal seizures: levetiracetam fails to topple phenobarbital as first-line therapy

  • Sharpe C & al.
  • Pediatrics
  • 08.05.2020

  • von Susan London
  • Clinical Essentials
Der Zugang zum gesamten Inhalt dieser Seite ist nur Angehörigen medizinischer Fachkreise vorbehalten. Der Zugang zum gesamten Inhalt dieser Seite ist nur Angehörigen medizinischer Fachkreise vorbehalten.

Takeaway

  • 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.

Key results

  • 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).
  • 70% of the phenobarbital group attained outcome with the initial 20 mg/kg loading dose.
  • Escalating levetiracetam dose from 40 to 60 mg/kg improved efficacy by 7.5%.
  • Adverse effects were nonsignificantly more common with phenobarbital:
    • 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).

Study design

  • 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.

Limitations

  • 23 infants excluded from modified intention-to-treat population.
  • Seizures possibly resolved spontaneously in some cases.
  • Use of short-term endpoint.