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Levetiracetam Treatment of Neonatal Seizures

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ClinicalTrials.gov Identifier: NCT02550028
Recruitment Status : Active, not recruiting
First Posted : September 15, 2015
Last Update Posted : May 1, 2019
Sponsor:
Collaborators:
Xiamen Children's Hospital, Fujian of China
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
Guangzhou Women and Children's Medical Center
Second Affiliated Hospital of Wenzhou Medical University
Maternal and Child Health Hospital of Hubei Province
The Maternal & Children Health Hospital of Dehong, Yunnan of China
Information provided by (Responsible Party):
Children's Hospital of Fudan University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Neonatal Seizures Drug: Oral levetiracetam Drug: Intravenous phenobarbital Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : September 2015
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Seizures

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 Name: 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 Name: phenobarbitone




Primary Outcome Measures :
  1. EEG [ Time Frame: At Day 28 ]
    Efficacy of levetiracetam by assessment of the change from baseline in EEG on Day 15.


Secondary Outcome Measures :
  1. 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.

  2. 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).

  3. 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.

  4. 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.

  5. Number of Adverse Events(Abnormal Blood Pressure) [ Time Frame: From Day 1 to Day 28 post-dose in each period ]
  6. Number of Adverse Events(Pulse) [ Time Frame: From Day 1 to Day 28 post-dose in each period ]
  7. Number of Adverse Events(Respiratory) [ Time Frame: From Day 1 to Day 28 post-dose in each period ]
  8. 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.

  9. 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.

  10. 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.


Other Outcome Measures:
  1. 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).

  2. 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).

  3. 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).

  4. 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).

  5. 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).

  6. 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).

  7. 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).

  8. 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)

  9. 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.



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Ages Eligible for Study:   up to 28 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02550028


Locations
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China, Shanghai
Children Hospital of Fudan University
Shanghai, Shanghai, China, 201102
Sponsors and Collaborators
Children's Hospital of Fudan University
Xiamen Children's Hospital, Fujian of China
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
Guangzhou Women and Children's Medical Center
Second Affiliated Hospital of Wenzhou Medical University
Maternal and Child Health Hospital of Hubei Province
The Maternal & Children Health Hospital of Dehong, Yunnan of China
Investigators
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Study Chair: Wenhao Zhou, Doctor Children's Hospital of Fudan University

Publications:

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Responsible Party: Children's Hospital of Fudan University
ClinicalTrials.gov Identifier: NCT02550028     History of Changes
Obsolete Identifiers: NCT02602015
Other Study ID Numbers: CHFudanU_NNICU3
First Posted: September 15, 2015    Key Record Dates
Last Update Posted: May 1, 2019
Last Verified: April 2019
Keywords provided by Children's Hospital of Fudan University:
Neonates
Seizure
Additional relevant MeSH terms:
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Levetiracetam
Seizures
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Phenobarbital
Anticonvulsants
Nootropic Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
GABA Modulators
GABA Agents
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers