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Emergency treatment with levetiracetam or phenytoin in status epilepticus in children-the EcLiPSE study: study
Mark D Lyttle1,2, Carrol Gamble3, Shrouk Messahel4
1Bristol Royal Hospital for Children, Bristol, UK.
Insights
This trial compares intravenous phenytoin and levetiracetam for treating childhood convulsive status epilepticus (CSE). It aims to find the most effective and safest second-line treatment for this pediatric neurological emergency.
Area of Science:
- Pediatric Neurology
- Emergency Medicine
- Clinical Pharmacology
Background:
- Convulsive status epilepticus (CSE) is a critical pediatric neurological emergency with significant morbidity.
- Current second-line treatments like intravenous phenytoin have limited evidence and potential side effects.
- Intravenous levetiracetam shows promise as a safer alternative for CSE treatment.
Purpose of the Study:
- To compare the efficacy of intravenous phenytoin versus levetiracetam as a second-line treatment for childhood CSE.
- To evaluate the safety profile of both phenytoin and levetiracetam in pediatric CSE management.
- To provide evidence-based recommendations for the second-line treatment of CSE in children.
Main Methods:
- Phase IV, multi-center, randomized controlled, open-label trial.
- Children with ongoing seizures after first-line treatment are randomized to receive either phenytoin or levetiracetam.
- Primary outcome: cessation of visible CSE signs; Secondary outcomes: need for further treatment, critical care admission, adverse reactions.
Main Results:
- The trial is designed to detect a significant difference in CSE cessation rates between phenytoin and levetiracetam.
- Sample size of 308 participants to ensure adequate power for primary outcome analysis.
- Deferred consent sought for eligible patients to facilitate timely enrollment.
Conclusions:
- This study will determine the comparative effectiveness and safety of phenytoin and levetiracetam for pediatric CSE.
- Findings will inform clinical guidelines for managing this life-threatening condition in children.
- Evidence generated will support optimal therapeutic strategies for childhood convulsive status epilepticus.
Background:
Convulsive status epilepticus (CSE) is the most common life-threatening neurological emergency in childhood. These children are also at risk of significant morbidity, with acute and chronic impact on the family and the health and social care systems. The current recommended first-choice, second-line treatment in children aged 6 months and above is intravenous phenytoin (fosphenytoin in the USA), although there is a lack of evidence for its use and it is associated with significant side effects. Emerging evidence suggests that intravenous levetiracetam may be effective as a second-line agent for CSE, and fewer adverse effects have been described. This trial therefore aims to determine whether intravenous phenytoin or levetiracetam is more effective, and safer, in treating childhood CSE.
Methods/Design:
This is a phase IV, multi-centre, parallel group, randomised controlled, open-label trial. Following treatment for CSE with first-line treatment, children with ongoing seizures are randomised to receive either phenytoin (20 mg/kg, maximum 2 g) or levetiracetam (40 mg/kg, maximum 2.5 g) intravenously. The primary outcome measure is the cessation of all visible signs of CSE as determined by the treating clinician. Secondary outcome measures include the need for further anti-seizure medications or rapid sequence induction for ongoing CSE, admission to critical care areas, and serious adverse reactions. Patients are recruited without prior consent, with deferred consent sought at an appropriate time for the family. The primary analysis will be by intention-to-treat. The primary outcome is a time to event outcome and a sample size of 140 participants in each group will have 80% power to detect an increase in CSE cessation rates from 60% to 75%. Our total sample size of 308 randomised and treated participants will allow for 10% loss to follow-up.
Discussion:
This clinical trial will determine whether phenytoin or levetiracetam is more effective as an intravenous second-line agent for CSE, and provide evidence for management recommendations. In addition, this trial will also provide data on which of these therapies is safer in this setting.
Trial Registration:
ISRCTN identifier, ISRCTN22567894 . Registered on 27 August 2015 EudraCT identifier, 2014-002188-13 . Registered on 21 May 2014 NIHR HTA Grant: 12/127/134.
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