Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a
Mark D Lyttle1, Naomi E A Rainford2, Carrol Gamble3
1Emergency Department, Bristol Royal Hospital for Children, Bristol, UK; Faculty of Health and Applied Sciences, University of the West of England, Bristol, UK.
Insights
Levetiracetam showed comparable efficacy to phenytoin for treating paediatric convulsive status epilepticus. This suggests levetiracetam may be a suitable alternative due to its safety and ease of administration.
Area of Science:
- Neurology
- Clinical Pharmacology
- Paediatric Emergency Medicine
Background:
- Phenytoin is the standard second-line intravenous anticonvulsant for paediatric convulsive status epilepticus in the UK.
- Levetiracetam is proposed as a potentially safer and effective alternative.
Purpose of the Study:
- To compare the efficacy and safety of levetiracetam versus phenytoin as second-line treatment for paediatric convulsive status epilepticus.
Main Methods:
- An open-label, randomized clinical trial involving 286 paediatric patients across 30 UK emergency departments.
- Participants received either levetiracetam (40 mg/kg) or phenytoin (20 mg/kg).
- Primary outcome was time to cessation of convulsive status epilepticus.
Main Results:
- Seventy percent of levetiracetam patients and 64% of phenytoin patients achieved seizure cessation.
- Median time to cessation was 35 minutes for levetiracetam vs. 45 minutes for phenytoin (HR 1.20, 95% CI 0.91-1.60; p=0.20).
- One death occurred in the levetiracetam group (unrelated), and one serious adverse reaction in the phenytoin group.
Conclusions:
- Levetiracetam demonstrated non-inferior efficacy to phenytoin in paediatric convulsive status epilepticus.
- Considering safety and ease of administration, levetiracetam is a viable alternative to phenytoin.
- Levetiracetam may be considered a first-choice, second-line anticonvulsant for this condition.
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.
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