The efficacy and safety of lorazepam were not superior to diazepam in a clinical trial of pediatric status epilepticus, investigators reported online April 22 in JAMA.
Both drugs effectively halted status epilepticus in more than 70% of children and adolescents and caused severe respiratory depression in less than 20%, said Dr. James Chamberlain of the Children’s National Medical Center, Washington, and his associates in the Pediatric Emergency Care Applied Research Network (PECARN).
"Taken together with the results of the RAMPART trial, it would appear that either diazepam, lorazepam, or midazolam could be chosen as a reasonable first-line therapy" for pediatric status epilepticus, the researchers said. Many prehospital systems prefer diazepam because it does not require refrigeration, they noted (JAMA 2014;311:1652-60 [doi:10.1001/jama.2014.2625]).
The multicenter, randomized, double-blind trial included 272 patients aged 3 months to less than 18 years who presented to one of 11 academic pediatric emergency departments with generalized tonic-clonic convulsive status epilepticus. Patients received intravenous diazepam (0.2 mg/kg) or lorazepam (0.1 mg/kg), with half the dose repeated at 5 minutes if needed. If status epilepticus continued at 12 minutes, patients received fosphenytoin or phenytoin.
Status epilepticus ceased by 10 minutes and did not recur for at least 30 minutes in 97 (72.9%) patients given lorazepam and in 101 (72.1%) patients treated with diazepam. The absolute efficacy difference was 0.8% (95% confidence interval, –11.4% to 9.8%). Severe respiratory depression – the primary safety outcome – occurred in 17.6% of lorazepam patients and 16.0% of diazepam patients, for an absolute risk difference of just 1.6% (95% CI, –9.9% to 6.8%), Dr. James Chamberlain and his associates reported.
Rates of secondary outcomes also were similar, except that sedation was more common in the lorazepam group (66.9% vs. 50% for diazepam; absolute risk difference, 16.9%; 95% CI, 6.1% to 27.7%).
The study was a superiority trial, not a noninferiority trial, so the two drugs could not be assumed to be statistically equivalent, the researchers said. "Although the point estimates for both efficacy and safety outcomes are similar in the two groups, the confidence intervals suggest that one medication could be superior in efficacy by as much as approximately 10% to 11% and in safety by approximately 7% to 10%," they wrote. They concluded that new treatment options for pediatric status epilepticus are needed, given the extent of medication failure and respiratory depression observed in both study groups.
The Eunice Kennedy Shriver National Institute of Child Health and Human Development funded the study. Dr. Pamela Okada reported receiving a grant from NICHD during the study. Dr. Prashant Mahajan, Dr. Richard Lichenstein, and Dr. Joseph Grubenhoff reported having received grants from the National Institutes of Health during the study. The remaining authors reported no relevant financial disclosures.