Levetiracetam Treatment of Neonatal Seizures

Study Overview
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Brief Summary
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Current treatments for the brain damaging complication of neonatal seizures are unsatisfactory. A multi-centre Chinese clinical trials with the aim to using oral Levetiracetam to develop new treatment strategies for the treatment of neonatal seizures. The purpose of this study is to determine the correct oral dosing, safety and efficacy for oral Levetiracetam as first line treatment in term new born babies with seizures.

Detailed Description
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This project aims to improve the treatment of neonatal seizures. Current treatments are poorly effective and have significant side effects. Levetiracetam has great potential as a treatment for neonatal seizures but is not approved for use in children less than 1 years of age by oral. This study aims to obtain essential data regarding the efficacy and safety of oral Levetiracetam in neonatal population and simultaneously to use EEG monitoring systems that facilitate seizure detection and research. Specific aims are: To determine the efficacy of oral Levetiracetam in terminating neonatal seizures by EEG in the Neonatal Neurological Intensive Care Unit (NNICU). To determine dose escalation data by studying the additional efficacy of a further dose in non responders. To determine additional pharmacokinetic data to confirm findings from our previous pharmacokinetic study. To determine further safety data of oral Levetiracetam in neonates.

Official Title
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Levetiracetam Treatment of Neonatal Seizures: A Multi-Centre Randomized Blinded Controlled Study of the Efficacy of Oral Levetiracetam as First Line Treatment for Neonatal Seizures in China

Conditions
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Neonatal Seizures

Intervention / Treatment
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* Drug: Oral levetiracetam
* Drug: Intravenous phenobarbital


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Neonatal seizure occurred and was proved by EEG according to abnormal discharge of brain. one or more of the following : Male or female term baby with gestational >37 weeks and postnatal age < or= 28 days Birthweight >2500g Written informed consent of parent or guardian Exclusion Criteria: Babies who have been close to death Seizure occurred by metabolic factors (hypoglycemia, hypocalcemia, electrolyte disorder) Babies who have received phenobarbitone or any other anticonvulsive medication before hospitalization Abnormal renal function

Ages Eligible for Study
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Maximum Age: 28 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral levetiracetam<br>Oral levetiracetam 50 mg/kg loading dose. 10 mg/kg 8 hourly maintenance | Drug: Oral levetiracetam<br>* Oral load of levetiracetam (50 mg/kg) following identification of EEG confirmed neonatal seizure.<br>* Other names: Keppra;|
| Active Comparator: Intravenous phenobarbital<br>Intravenous phenobarbital 20 loading dose (add to 40 mg/kg if seizure discontrol). 5 mg/kg 24 hourly maintenance | Drug: Intravenous phenobarbital<br>* Intravenous load of phenobarbital (20 mg/kg)following EEG confirmation of seizure activity load.<br>* Other names: phenobarbitone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EEG | Efficacy of levetiracetam by assessment of the change from baseline in EEG on Day 15. | At Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain Parenchyma Alterations(MRI) | Efficacy of levetiracetam by assessment of the change of brain from baseline in MRI on Day 28. | At Day 28 | 
| Neurodevelopment(Bayley Scores) | Efficacy of levetiracetam by assessment of the change from baseline to Day 28 in neurodevelopment via Bayley Scores of Infant Development Mental Development Index (BSID). | At Day 28 | 
| Seizure Control Days | Efficacy of levetiracetam by assessment of seizure control days. | From Day 1 to Day 28 post-dose in each period | 
| Number of Adverse Events（Abnormal Appearance） | This is a composition of general appearance, abdomen, skin, head and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems. | From Day 1 to Day 28 post-dose in each period | 
| Number of Adverse Events（Abnormal Blood Pressure） |  | From Day 1 to Day 28 post-dose in each period | 
| Number of Adverse Events(Pulse) |  | From Day 1 to Day 28 post-dose in each period | 
| Number of Adverse Events(Respiratory) |  | From Day 1 to Day 28 post-dose in each period | 
| Number of Abnormal Clinical Chemistry | Safety of levetiracetam by assessment of safety laboratory tests. | From Day 1 to Day 28 post-dose in each period | 
| Number of Abnormal Hematology | Safety of levetiracetam by assessment of safety laboratory tests. | From Day 1 to Day 28 post-dose in each period | 
| Number of Abnormal Clinical Urinalysis | Safety of levetiracetam by assessment of safety laboratory tests. | From Day 1 to Day 28 post-dose in each period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neonates, Seizure