ESETT (valproate vs. fosphenytoin)
Trial question
What is the effect of valproate in patients with benzodiazepine-refractory convulsive status epilepticus?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
43.0% female
57.0% male
N = 239
239 patients (103 female, 136 male).
Inclusion criteria: patients with benzodiazepine-refractory convulsive status epilepticus.
Key exclusion criteria: acute precipitant of seizure was major trauma, hypoglycemia, hyperglycemia, cardiac arrest, or postanoxia; pregnancy; incarceration; treatment for the current episode of status epilepticus with anticonvulsant agents other than benzodiazepines or tracheal intubation; allergy or contraindications to trial drugs.
Interventions
N=121 valproate (at a dose of 40 mg/kg, maximum dose of 3,000 mg).
N=118 fosphenytoin (at a dose of 20 mg/kg, maximum dose of 1,500 mg PE).
Primary outcome
Cessation of seizures and improvement in consciousness at 60 minutes without other anticonvulsant medications
46%
45%
46.0 %
34.5 %
23.0 %
11.5 %
0.0 %
Valproate
Fosphenytoin
No significant
difference ↔
No significant difference in cessation of seizures and improvement in consciousness at 60 minutes without other anticonvulsant medications (46% vs. 45%; AD 1.3%, 95% CI -11.1 to 13.8).
Safety outcomes
No significant differences in hypotension, endotracheal intubation, death.
Conclusion
In patients with benzodiazepine-refractory convulsive status epilepticus, valproate was not superior to fosphenytoin with respect to cessation of seizures and improvement in consciousness at 60 minutes without other anticonvulsant medications.
Reference
Jaideep Kapur, Jordan Elm, James M Chamberlain et al. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. N Engl J Med. 2019 Nov 28;381(22):2103-2113.
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