Outpatient nasal midazolam spray controls seizure clusters

  • Detyniecki K & al.
  • Epilepsia
  • 29 May 2019

  • International Clinical Digest
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Takeaway

  • Compared with placebo, nasal midazolam spray provided rapid, sustained seizure control in patients with seizure clusters with a good safety profile.

Why this matters

  • Limited options for treating seizure clusters outside of medical settings by nonclinicians.

Key results

  • Compared with placebo group, nasal midazolam group had:
    • Higher rate of treatment success (53.7% vs 34.3%; P=.0109).
    • Lower rate of seizure recurrence (38.1% vs 59.7%; P=.0043).
    • Longer time to next seizure (probability of no seizure at 24 hours, 58.3% vs 37.1%; P=.0124).
  • During double-blind phase, midazolam and placebo groups similar on:
    • Treatment-emergent adverse events (26.4% vs 23.1%).
    • Discontinuation due to treatment-emergent adverse events (0% vs 0%).
  • Leading treatment-emergent adverse events with midazolam during double-blind phase: somnolence (9.9%), headache (6.6%), nasal discomfort (5.5%).

Study design

  • International phase 3 randomized controlled trial: 292 patients aged ≥12 years on a stable regimen of antiepileptic drugs for seizure clusters (ARTEMIS‐1 trial).
  • After in-clinic test dose phase, randomized 2:1 to 6-month double-blind phase: midazolam nasal spray 5 mg vs placebo nasal spray, administered by caregivers for seizure cluster.
  • Main outcome: treatment success (seizure termination within 10 minutes and no recurrence 10 minutes to 6 hours thereafter).
  • Funding: Proximagen LLC.

Limitations

  • Trial stopped early.
  • No active comparator.