Efficacy of Intravenous Levetiracetam in Neonatal Seizures

Neonatal Seizures Clinical Trial

— NEOLEV2  

Official title:

Efficacy of Intravenous Levetiracetam in Neonatal Seizures: A Phase 2 Randomized Blinded Controlled Study of the Efficacy of Intravenous Levetiracetam (LEV) as First Line Treatment for Neonatal Seizures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01720667
• Other study ID #: NoGA - R01 FD004147-01A1 Haas
• Secondary ID: 1R01FD004147-01A
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2013
• Est. completion date: July 31, 2019

Study information

• Verified date: August 2019
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A new anticonvulsant, levetiracetam will be studied to treat seizures in newborn infants. Current treatments for the brain damaging complication of neonatal seizures are unsatisfactory.

Monitoring for seizure detection will be tested at five (5) US sites and one (1) international site using the internet.

Description:

This project aims to improve the treatment of neonatal seizures. Current treatments are poorly effective and have significant side effects.

Levetiracetam (LEV) has great potential as a treatment for neonatal seizures but is not approved for use in children less than 2 years of age.

This study aims to obtain essential data regarding the efficacy and safety of LEV in this vulnerable and under researched population and simultaneously to develop EEG monitoring systems that facilitate seizure detection and research.

Specific aims are:

1. To determine the efficacy of intravenous LEV in terminating neonatal seizures when given as first line therapy.

2. To obtain dose escalation data by studying the additional efficacy of a further dose in non responders.

3. To obtain additional pharmacokinetic data to confirm findings from our previous pharmacokinetic study.

4. To obtain further safety data of LEV in neonates.

5. To prove the feasibility of centralized remote monitoring of continuous EEG monitoring in the Neonatal Intensive Care Unit (NICU) via the internet and test a promising automated neonatal seizure detection algorithm.

The study design is a phase 2b randomized blinded controlled study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 280
• Est. completion date: July 31, 2019
• Est. primary completion date: October 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 14 Days

Eligibility

Inclusion Criteria:

1. Newborns admitted to any of the study sites with electrographic seizures seizures.

2. Term infants gestational age >36 weeks less than 2 weeks of age.

3. Greater than 2200 grams.

4. Infants for whom parental consent to participate in the study is obtained.

Exclusion Criteria:

1. Infants who are already receiving anticonvulsants

2. If serum creatinine is greater than 1.6mM

3. If seizures are due to correctable metabolic abnormalities (i.e. hypoglycaemia, hypocalcemia, hyponatremia)

4. Subjects in whom death seems imminent, as assessed by the neonatologist.

Related Conditions & MeSH terms

• Neonatal Seizures
• Seizures

Intervention

Drug:
• Intravenous levetiracetam
Intravenous load of levetiracetam (40 to 60 mg/kg) following identification of EEG confirmed neonatal seizure.
• Intravenous phenobarbital
Intravenous load of phenobarbital (20 to 40 mg/kg) following EEG confirmation of seizure activity load.

Locations

Country	Name	City	State
United States	University of California, San Diego Medical Center / Neonatal Intensive Care Unit (NICU)	San Diego	California

Sponsors (7)

Lead Sponsor	Collaborator
Richard H. Haas	Auckland City Hospital, Food and Drug Administration (FDA), Rady Children's Hospital, San Diego, Sharp Mary Birch Hospital for Women & Newborns, UCSF Benioff Children’s Hospital Oakland, University of California, San Diego

Country where clinical trial is conducted

United States, 

References & Publications (2)

Sharpe C, Davis SL, Reiner GE, Lee LI, Gold JJ, Nespeca M, Wang SG, Joe P, Kuperman R, Gardner M, Honold J, Lane B, Knodel E, Rowe D, Battin MR, Bridge R, Goodmar J, Castro B, Rasmussen M, Arnell K, Harbert M, Haas R. Assessing the Feasibility of Providin — View Citation

Sharpe CM, Capparelli EV, Mower A, Farrell MJ, Soldin SJ, Haas RH. A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life. Pediatr Res. 2012 Jul;72(1):43-9. doi: 10.1038/pr.2012.51. Epub 2012 Apr 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacokinetic Data	To obtain additional pharmacokinetic data "Area under the plasma concentration versus time curve (AUC) and Peak Plasma Concentration (Cmax)" of intravenous levetiracetam to confirm findings from our previous pharmacokinetic study.	48 hours
Other	Feasibility of Continuous Internet EEG Monitoring	Feasibility of centralized remote access to continuous video EEG monitoring in the NICU via the internet	Subject study duration
Other	Evaluation of the Accuracy of Neonatal Seizure Detection Algorithm	A novel neonatal seizure detection algorithm will be compared to the gold standard of two encephalographers reading 48 hours of neonatal video EEG in the measurement of seizure burden.	48 Hours
Other	Gather Safety Information on IV Levetiracetam	Safety information to be collected includes daily recording of any adverse events during the 5 day treatment protocol.; Complete Blood Count and Comprehensive Chemistry panels after 48 hours of treatment collected.	5 days
Primary	Neonates With Seizure Cessation When Given Levetiracetam (40-60 mg/kg) as First Line Therapy Compared to Phenobarbital (20-40mg/kg)	A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.; Seizure cessation from 15 minutes after completion of infusion for 24 hours as assessed by continuous EEG reviewed by neurophysiologists.	24 hours
Secondary	Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital at 48 Hours After Treatment	A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.	48 hours
Secondary	Number of Neonates With Seizure Termination at 1 Hour After Treatment	A head to head comparison of the efficacy of intravenous levetiracetam versus phenobarbital in the treatment of EEG proven neonatal seizures.	1 hour
Secondary	LEV Dose Escalation Component	Number of babies with seizure control at levetiracetam (60 mg/Kg load) who had not responded to 40 mg/kg load and number of babies with seizure control at 40 mg/kg who had not responded to 20 mg/kg.	24 hours
Secondary	Neonates With Seizure Cessation When Given Levetiracetam as First Line Therapy Compared to Phenobarbital Within the Hypoxic Ischemic Encephalopathy (HIE) Population and Treated With Hypothermia		24 hours