Comparison of Phenytoin, Valproate and Levetiracetam in Pediatric Convulsive Status Epilepticus: A Randomized Double-blind Controlled Clinical Trial.

OBJECTIVE

To compare the efficacy of phenytoin, valproate, and levetiracetam in the management of pediatric convulsive status epilepticus.

DESIGN

Randomized double-blind controlled clinical trial.

SETTING

Pediatric critical care division in a tertiary care institute from June, 2016 to December, 2018.

PARTICIPANTS

110 children aged three month to 12 year with convulsive status epilepticus.

INTERVENTION: Patients not responding to 0.1 mg/kg intravenous lorazepam were randomly assigned (1:1:1) to receive 20 mg/kg of phenytoin (n=35) or valproate (n=35) or levetiracetam (n=32) over 20 minutes. Patients with nonconvulsive status epilepticus, recent hemorrhage, platelet count less than 50,000 or International normalized ratio (INR) more than 2, head injury or neurosurgery in the past one-month, liver or kidney disease, suspected or known neurometabolic or mitochondrial disorders or structural malformations, and allergy to study drugs; and those who were already on any one of the study drugs for more than one month or had received one of the study drugs for current episode, were excluded.

OUTCOME MEASURE: The primary outcome was the proportion of patients that achieved control of convulsive status epilepticus at the end of 15 minutes after completion of the study drug infusion. Secondary outcomes were time to control of seizure, rate of adverse events, and the requirement of additional drugs to control seizure, length of ventilation, hospital stay, and functional status after three months (Glasgow Outcome Scale).

RESULTS

The study was stopped after the planned mid-interim analysis for futility. Intention to treat analysis was done. There was no difference in primary outcome in phenytoin (31/35, 89%), valproate (29/35, 83%), and levetiracetam (30/32, 94%) (P=0.38) groups. There were no differences between the groups for secondary outcomes. One patient in the phenytoin group had a fluid-responsive shock, and one patient in the valproate group died due to encephalopathy and refractory shock.

CONCLUSIONS

Phenytoin, valproate, and levetiracetam were equally effective in controlling pediatric convulsive status epilepticus.