Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for adult convulsive status epilepticus: a multicentre non-inferiority randomised control trial

J Neurol Neurosurg Psychiatry. 2023 Jan;94(1):42-48. doi: 10.1136/jnnp-2022-329485. Epub 2022 Oct 7.

Abstract

Objective: Status epilepticus (SE) is an emergency condition for which rapid and secured cessation is crucial. Although fosphenytoin (FPHT) is recommended as a second-line treatment, levetiracetam (LEV) reportedly has similar efficacy, but higher safety. Therefore, we herein compared LEV with FPHT in adult SE.

Methods: We initiated a multicentre randomised control trial in emergency departments with adult patients with convulsive SE. Diazepam was initially administered, followed intravenously by FPHT at 22.5 mg/kg or LEV at 1000-3000 mg. The primary outcome was assigned as the seizure cessation rate within 30 min of the administration of the study drug.

Results: A total of 176 adult patients with SE were enrolled (82 FPHT and 94 LEV), and 3 were excluded from the full analysis set. Seizure cessation rates within 30 min were 83.8% (67/80) in the FPHT group and 89.2% (83/93) in the LEV group. The difference in these rates was 5.5% (95% CI -4.7 to 15.7, p=0.29). The non-inferiority of LEV to FPHT was confirmed with p<0.001 by the Farrington-Manning test. No significant differences were observed in the seizure recurrence rate or intubation rate within 24 hours. Serious adverse events developed in three patients in the FPHT group and none in the LEV group (p=0.061).

Conclusion: The efficacy of LEV was similar to that of FPHT for adult SE following the administration of diazepam. LEV may be recommended as a second-line treatment for SE along with phenytoin/FPHT.

Trial registration number: jRCTs031190160.

Keywords: EPILEPSY; MEDICINE.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticonvulsants / adverse effects
  • Diazepam / therapeutic use
  • Humans
  • Levetiracetam / adverse effects
  • Levetiracetam / therapeutic use
  • Phenytoin* / adverse effects
  • Phenytoin* / therapeutic use
  • Seizures / drug therapy
  • Status Epilepticus* / drug therapy
  • Treatment Outcome

Substances

  • Levetiracetam
  • fosphenytoin
  • Phenytoin
  • Diazepam
  • Anticonvulsants