Summary
Background
Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.
Methods
This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.
Findings
Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]).
Interpretation
Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus.
Funding
National Institute for Health Research Health Technology Assessment programme.
Differences in injury patterns and mortality exist between different age groups and high-risk injury patterns can be identified. With increasing age, a decline in the proportion of children with head injury and an increase in the proportion with limb injury were observed. This information is useful for directing ongoing care of severely injured children. Future analyses of the TARN database may help to evaluate the management of high-risk children and to identify the most effective care.
Question: For children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward (within 48 hours), is subsequent outpatient treatment with oral amoxicillin at a dose of 35-50 mg/kg/day noninferior to 70-90 mg/kg/day, and for 3 days noninferior to 7 days, with regard to the need for antibiotic retreatment? Findings: In this 2x2 factorial randomized clinical trial of 814 children requiring amoxicillin for community-acquired pneumonia at hospital discharge, antibiotic retreatment within 28 days occurred in 12.6% vs 12.4% of those randomized to lower vs higher doses, respectively, and in 12.5% vs 12.5% of those randomized to 3-day vs 7-day amoxicillin duration. Both comparisons met the prespecified 8% noninferiority margin.Meaning: Among children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward, further outpatient treatment with oral amoxicillin at a dose of 35-50 mg/kg/day was noninferior to a dose of 70-90 mg/kg/day and for 3 days was noninferior to 7 days with regard to the need for later antibiotic retreatment.
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