Levetiracetam Treatment of Neonatal Seizures

December 27, 2023 updated by: Children's Hospital of Fudan University

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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:

  1. To determine the efficacy of oral Levetiracetam in terminating neonatal seizures by EEG in the Neonatal Neurological Intensive Care Unit (NNICU).
  2. To determine dose escalation data by studying the additional efficacy of a further dose in non responders.
  3. To determine additional pharmacokinetic data to confirm findings from our previous pharmacokinetic study.
  4. To determine further safety data of oral Levetiracetam in neonates.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 201102
        • Children Hospital of Fudan University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 4 weeks (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Neonatal seizure occurred and was proved by EEG according to abnormal discharge of brain. one or more of the following :

  1. Male or female term baby with gestational >37 weeks and postnatal age < or= 28 days
  2. Birthweight >2500g
  3. Written informed consent of parent or guardian

Exclusion Criteria:

  1. Babies who have been close to death
  2. Seizure occurred by metabolic factors (hypoglycemia, hypocalcemia, electrolyte disorder)
  3. Babies who have received phenobarbitone or any other anticonvulsive medication before hospitalization
  4. Abnormal renal function

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
EEG
Time Frame: At Day 28
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)
Time Frame: At Day 28
Efficacy of levetiracetam by assessment of the change of brain from baseline in MRI on Day 28.
At Day 28
Neurodevelopment(Bayley Scores)
Time Frame: At Day 28
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
Time Frame: From Day 1 to Day 28 post-dose in each period
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）
Time Frame: From Day 1 to Day 28 post-dose in each period
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）
Time Frame: From Day 1 to Day 28 post-dose in each period
From Day 1 to Day 28 post-dose in each period
Number of Adverse Events(Pulse)
Time Frame: From Day 1 to Day 28 post-dose in each period
From Day 1 to Day 28 post-dose in each period
Number of Adverse Events(Respiratory)
Time Frame: From Day 1 to Day 28 post-dose in each period
From Day 1 to Day 28 post-dose in each period
Number of Abnormal Clinical Chemistry
Time Frame: From Day 1 to Day 28 post-dose in each period
Safety of levetiracetam by assessment of safety laboratory tests.
From Day 1 to Day 28 post-dose in each period
Number of Abnormal Hematology
Time Frame: From Day 1 to Day 28 post-dose in each period
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
Time Frame: From Day 1 to Day 28 post-dose in each period
Safety of levetiracetam by assessment of safety laboratory tests.
From Day 1 to Day 28 post-dose in each period

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate and extent of absorption by assessment of tmax
Time Frame: At Day 1 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
Comparison of tmax (time to reach maximum plasma concentration) of levetiracetam on Day 1 of each treatment period; up to 6 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose).
At Day 1 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
Rate and extent of absorption by assessment of Cmax
Time Frame: At Day 1 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
Comparison of Cmax (maximum observed plasma concentration) of levetiracetam on Day 1 of each treatment period; up to 6 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose).
At Day 1 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
Rate and extent of absorption by assessment of AUC(0-4)
Time Frame: At Day 1 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
Comparison of AUC(0-4) (Area under the plasma concentration-time curve from time zero to 4 hours after administration) of levetiracetam on Day 1 of each treatment period; up to 6 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose).
At Day 1 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
Rate and extent of absorption by assessment of Cmax,ss of levetiracetam
Time Frame: At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Comparison of Cmax,ss (observed maximum plasma concentration at steady state) of levetiracetam on Day 14 of each treatment period; up to 10 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose).
At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Rate and extent of absorption by assessment of AUC(0-24) of levetiracetam
Time Frame: At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Comparison of AUC(0-24) (Area under the plasma concentration-time curve from time zero to 24 hours after administration) of levetiracetam on Day 14 of each treatment period; up to 10 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose).
At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Rate and extent of absorption by assessment of tmax,ss of levetiracetam
Time Frame: At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Comparison of tmax,ss (time to reach maximum plasma concentration at steady state) of levetiracetam on Day 14 of each treatment period; up to 10 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose).
At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Rate and extent of absorption by assessment of Cavg,ss of levetiracetam
Time Frame: At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Comparison of Cavg,ss (average plasma concentration during a dosing interval at steady state) of levetiracetam on Day 14 of each treatment period; up to 10 samples will be collected in each period (i.e. in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose).
At Day 14 in each period (in subjects with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Rate and extent of absorption by assessment of AUC(0-last) of levetiracetam
Time Frame: At Day 1 and Day 14 in each period (in subjects with intensive pharmacokinetic assessments, on Day 1 at pre-dose and 15 and 30 minutes, and 1, 2 and 4 h post-dose, on Day 14 at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Comparison of AUC(0-last) (Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration) of levetiracetam (i.e. in subjects with intensive pharmacokinetic assessments)
At Day 1 and Day 14 in each period (in subjects with intensive pharmacokinetic assessments, on Day 1 at pre-dose and 15 and 30 minutes, and 1, 2 and 4 h post-dose, on Day 14 at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Rate and extent of absorption following multiple dose administration by assessment of Cmin of levetiracetam
Time Frame: At Day 1 and on Day 14 at pre-dose in each period
Comparison of Cmin (predose concentration) of levetiracetam in each treatment period.
At Day 1 and on Day 14 at pre-dose in each period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital of Fudan University

Collaborators

Second Affiliated Hospital of Wenzhou Medical University
Guangzhou Women and Children's Medical Center
Maternal and Child Health Hospital of Hubei Province
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
Xiamen Children's Hospital, Fujian of China
The Maternal & Children Health Hospital of Dehong, Yunnan of China

Investigators

  • Study Chair: Wenhao Zhou, Doctor, Children's Hospital of Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2015

Primary Completion (Actual)

January 1, 2017

Study Completion (Actual)

January 1, 2017

Study Registration Dates

First Submitted

September 4, 2015

First Submitted That Met QC Criteria

September 13, 2015

First Posted (Estimated)

September 15, 2015

Study Record Updates

Last Update Posted (Actual)

December 29, 2023

Last Update Submitted That Met QC Criteria

December 27, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHFudanU_NNICU3

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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