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

Efficacy of Levetiracetam in Control of Neonatal Seizures

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

Study Overview

• Status: Unknown
• Conditions: Neonatal Seizures
• Intervention / Treatment: Drug: Levetiracetam; Drug: Phenobarbital

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yara S Shaheen, Msc; Phone Number: 002 01227981313; Email: yarasalah.shaheen@gmail.com
• Study Contact Backup: Name: Aliaa A Ali, MD; Email: draliaaadel@yahoo.com

Study Locations

• Egypt
  • Cairo Governorate, Egypt
    • Recruiting
    • Cairo University Children's Hospital (Abulreesh)
    • Contact: Yara Shaheen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 hour to 1 month (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Levetiracetam; 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; 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.
Active Comparator: Phenobarbital; 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; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To gather safety information on levetiracetam use in neonates	By collecting data of renal and liver function tests 48-72 hours after treatment.	72 hours

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Study Chair: Omneya G Afify, MD, Cairo University; Study Director: Iman F Iskander, MD, Cairo University; Principal Investigator: Aliaa A Ali, MD, Cairo University; Principal Investigator: Yara S Shaheen, MSc., Cairo University; Principal Investigator: Walaa Shaarany, MD, Cairo University

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2017
• Primary Completion (Anticipated): October 30, 2017
• Study Completion (Anticipated): December 30, 2017

Study Registration Dates

• First Submitted: February 22, 2017
• First Submitted That Met QC Criteria: April 5, 2017
• First Posted (Actual): April 11, 2017

Study Record Updates

• Last Update Posted (Actual): April 11, 2017
• Last Update Submitted That Met QC Criteria: April 5, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Levetiracetam; EEG with Periodic Abnormalities; Phenobarbitone; neonatal seizures; Neurodevelopmental Abnormality
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Seizures; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Hypnotics and Sedatives; GABA Modulators; GABA Agents; Anticonvulsants; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Nootropic Agents; Cytochrome P-450 CYP2B6 Inducers; Levetiracetam; Phenobarbital
• Other Study ID Numbers: YSShaheen

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No