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Kapur J, et al. "Randomized trial of three anticonvulsant medications for status epilepticus". The New England Journal of Medicine. 2019. 381(22):2103-2113.

Clinical Question

In patients with status epilepticus refractory to benzodiazepines, what is the efficacy and safety of the second-line anti-convulsants in aborting the seizure?

Bottom Line

In comparing levetiracetam, fosphenytoin, and valproate, they are all equally efficacious with a seizure cessation rate of approximately fifty percent and statistically similar rates of adverse events.

Major Points



  • Multicenter, blinded, parallel-group, randomized controlled trial
  • N=384
    • Levetiracetam (n=145) vs Fosphenytoin (n=118) vs Valproate (n=121)
  • Setting: 57 hospital emergency departments across the United States
  • Enrollment:
  • Mean follow-up:
  • Analysis: Intention-to-treat
  • Primary outcome: Abortion of status epilepticus and improvement of level of consciousness by 60 minutes


Inclusion Criteria

  • Older than 2 years old
  • Treated with accepted cumulative dose of benzodiazepines for status epilepticus and continued to have seizures
  • No more than 30 minutes had passed after last dose of benzodiazepine

Exclusion Criteria

  • If the acute precipitant of seizure was major trauma, hypoglycemia, hyperglycemia, cardiac arrest, or postanoxia
  • If the patient was pregnant or incarcerated
  • The patient preemptively opted out of this trial by wearing a medical alert tag marked “ESETT declined” (these tags were made available by the trial when requested)
  • If they had already been treated for the current episode of status epilepticus with anticonvulsant agents other than benzodiazepines
  • If the trachea was intubated
  • Known allergy or contraindications to any of the trial drugs, including known inborn metabolic disorder, liver disease, or severe renal impairment

Baseline Characteristics



Comparisons are intensive therapy vs. standard therapy.

Primary Outcomes

Abortion of status epilepticus and improvement of level of consciousness by 60 minutes

Secondary Outcomes

Subgroup Analysis

Adverse Events



  • National Institutes of Health
  • Federal Drug Administration

Further Reading