Efficacy of Levetiracetam in Control of Neonatal Seizures Guided by an EEG

Study Overview
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Brief Summary
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Over the last three decades, several tools have been developed to enhance the detection and treatment of neonatal seizures. Regarding treatment, phenobarbital maintains is still used as a first-line therapy worldwide. However, newer anti-epileptic drugs (AED) s such as, levetiracetam, bumetanide, and topiramate are increasingly being applied to the neonatal population, offering the potential for seizure treatment with a significantly better side-effect profile. Levetiracetam is a very promising medication for the treatment of neonatal seizures. It has been in clinical use for almost a decade in adults and older children with good efficacy, an excellent safety profile and near ideal pharmacokinetic characteristics. It has been approved and used for treatment of seizures in infants starting one month of age since 2012. The investigators are comparing the efficacy of levetiracetam to that of phenobarbital as a first-line drug in control of neonatal seizures. The investigators monitor the efficacy through assessment of frequency of seizures before and after drug administration, amplitude integrated EEG changes in background activity and seizure frequency in participants, duration taken for participants to be seizure free and short term neurodevelopmental outcome and EEG at 3 months of age

Official Title
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Efficacy of Levetiracetam in Control of Neonatal Seizures

Conditions
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Neonatal Seizures

Intervention / Treatment
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* Drug: Levetiracetam
* Drug: Phenobarbital


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All full term neonates experiencing seizures due to; post-hypoxic or post-ischemic encephalopathy, intracerebral hemorrhage, cerebral infection, inborn errors of metabolism or malformations of cortical development Exclusion Criteria: Preterm neonates Full term neonates with seizures due to metabolic derangements (hypoglycemia, hypocalcemia or hypomagnesemia) Full term neonates with impaired renal functions.

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 30 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Levetiracetam<br>Levetiracetam given in oral form via oro-gastric tube, first a bolus dose 40-50mg/kg then maintenance dose 10-30 mg/kg/day divided every 12 hours. Duration: until seizure free | Drug: Levetiracetam<br>* Given in a bolus dose first 50mg/kg as levetiracetam reaches a therapeutic serum level rapidly in 1.3 hours. Titration will not be attempted in our study to reach drug level rapidly and consequent rapid effective control of seizures. Maintenance dose is then given at a dose of 10 - 40mg/kg/day divided every 12 hours.<br>|
| Active Comparator: Phenobarbital<br>Phenobarbital given in IV form, loading dose 20mg/kg that can be repeated after a 20 minute interval not to exceed 40mg/kg then maintenance dose 2-4 mg/kg/day divided every 12 hours. Duration: until seizure free | Drug: Phenobarbital<br>* Phenobarbital is given intravenously in the form of a loading dose of 15mg/kg that can be repeated after a 20 minute interval not to exceed 30mg/kg then a maintenance dose 2-4 mg/kg/day divided every 12 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of levetiracetam in control of neonatal seizures as a first line versus phenobarbital through assessment of seizure burden. | Number of seizures before and after levetiracetam administration in comparison to phenobarbital. | 72 hours | 
| Efficacy of levetiracetam in rapid control of neonatal seizures compared to phenobarbital. | Number of hours taken to achieve seizure freedom after administration of levetiracetam versus phenobarbital. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose escalation data about levetiracetam through studying the efficacy of further dose administration in non responders. | Number of originally non responder participants who achieved seizure control with higher doses of levetiracetam. | 72 hours | 
| Adequacy of levetiracetam as a single agent antiepileptic drug in control of neonatal seizures. | Number of participants who require addition of second line antiepileptic drug to control seizures after levetiracetam versus phenobarbital use. | 30 days | 
| Accuracy of amplitude integrated EEG monitoring in detecting neonatal seizures before and after antiepileptic drug use. | Number of seizures detected by aEEG before and after antiepileptic drug use. | 48 hours | 
| Effect of levetiracetam on aEEG background activity of participants. | Number of participants with normalization of background activity after administration of levetiracetam versus phenobarbital. | 48 hours | 
| The short term clinical outcome of patients with neonatal seizures after treatment with levetiracetam. | Neurodevelopmental assessment through detecting presence of following milestones: Head control Social smile Visual fixation and pursuit Turning towards sounds | 3 months | 
| The short term electroencephalographic outcome of patients with neonatal seizures after treatment with levetiracetam | Number of participants with presence of epileptogenic activity on follow up electroencephalogram. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EEG with Periodic Abnormalities, Levetiracetam, Phenobarbitone, neonatal seizures, Neurodevelopmental Abnormality