Efficacy of Keppra for Neonatal Seizures

Safety, Tolerability, and Efficacy of Levetiracetam for Neonatal Seizures

The purpose of this research study is to learn how well the medication levetiracetam (Keppra) works to treat seizures in full term and premature babies. Levetiracetam is commonly used in babies with seizures at Cincinnati Children's Hospital, especially if the seizures have not been stopped by other medicines. The Food and Drug Administration (FDA) has approved the use of levetiracetam for older children (over the age of 4) but not for infants. Even though it is not FDA approved for this age group, doctors at Cincinnati Children's use the medicine as a second drug in babies whose seizures are not stopped by phenobarbital. Some doctors are concerned that phenobarbital is not the best medicine to treat seizures in babies, so researchers are trying to study other medicines.

In this study, the investigators are looking at how well levetiracetam stops or slows down seizures in babies. The investigators are also studying the blood levels of levetiracetam to learn more about how the medicine is processed by the body and what level of medicine in the body works to stop seizures. The investigators are checking labs before and after giving the dose to make sure the medication does not cause any changes in blood counts, kidney function, or liver function. The investigators are following all of the babies in the study after hospital discharge to see if the parents notice any side effects of the medication. Babies in the study will come back to the High Risk Follow Up Clinic at Cincinnati Children's at 6 months of age for a visit with a neurologist and a neonatologist and developmental testing.

Study Overview

• Status: Terminated
• Conditions: Neonatal Seizures
• Intervention / Treatment: Drug: levetiracetam

• Study Type: Observational
• Enrollment (Actual): 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45215
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 month (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

25 neonates ≥ 35 weeks of gestation and ≤ 30 days of life with electrographically-confirmed seizures

Description

Inclusion criteria:

• Gestational age ≥ 35 weeks
• Postnatal age ≤ 30 days
• Birth weight ≥ 2000 grams
• Clinical or electrographic seizures of any etiology requiring treatment with an antiepileptic medication (as per the judgment of the clinician caring for the patient)
• Parental consent obtained

Exclusion criteria:

• Infants with renal insufficiency indicated by serum creatinine > 2.0 (as part of pre-screening, labs obtained as part of routine care will be reviewed. Infants who have not had a creatinine drawn will have one drawn as part of the study after consent is obtained. If the baby requires levetiracetam emergently before the results of the creatinine are back, the dose will still be given and levels will still be drawn as per the protocol.
• Infants who have previously received levetiracetam
• Parents refuse consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Levetiracetam as first line; Babies who receive levetiracetam as a first line drug for seizures	Drug: levetiracetam; Infants in the both groups will receive 50 mg/kg IV levetiracetam after (continued) seizures are EEG confirmed.
Phenobarbital as first line; Babies who receive phenobarbital as a first line drug for seizures and levetiracetam as a second line drug	Drug: levetiracetam; Infants in the both groups will receive 50 mg/kg IV levetiracetam after (continued) seizures are EEG confirmed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy	The primary outcome is the proportion of infants who achieve electrographic seizure freedom as measured by continuous EEG monitoring for 24 hours after intravenous levetiracetam administration.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	Pharmacokinetic parameters and the concentration-response relationship will be determined by collecting 3 blood samples in the 24 hours after the dose (2-15 minutes post infusion, 1-2 hours post infusion, and 6-10 hours post infusion).	24 hours
Safety	Safety will be monitored by reviewing changes in vital signs and laboratory parameters after the dose.	7 days
Tolerability	Infants who remain on levetiracetam after discharge will be followed for 6 months to determine post-hospital treatment-emergent adverse events. All infants in the study will receive a 6 month developmental profile using the Bayley Scales of Infant Development.	6 months

Collaborators and Investigators

• Sponsor: Stephanie Merhar, MD
• Investigators: Principal Investigator: Stephanie L Merhar, MD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): August 1, 2012

Study Registration Dates

• First Submitted: November 17, 2011
• First Submitted That Met QC Criteria: November 18, 2011
• First Posted (ESTIMATE): November 21, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): April 19, 2013
• Last Update Submitted That Met QC Criteria: April 17, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Seizures; Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: 2011-1557