IV Levetiracetam for the Treatment of Neonatal Seizures: a Pharmacokinetic and Preliminary Efficacy and Safety Study
Summary
The purpose of this study is to determine the correct dosing for intravenous levetiracetam in term new born babies with seizures. In addition information on safety and efficacy will be collected. This new anticonvulsant drug is a promising treatment for seizures in newborns.
Description
There is a pressing need to improve the treatment of seizures in the neonatal period. The anticonvulsant agents currently in use may damage the developing brain and are quite ineffective at controlling seizures in neonates. Newborn seizures are common (1 in 300 newborns) and are associated with very poor outcomes. 20-30% of infants with neonatal seizures die, 20-30% develop epilepsy outside the neonatal period and 20-40% develop cerebral palsy and/or mental retardation. Better treatments for neonatal seizures could improve these outcomes.
An intravenous form of the anti-seizure medication levetiracetam has been released for use in adults with epilepsy. Experience with oral levetiracetam has shown it to be a very safe medication, with good efficacy in stopping seizures in other age groups. The intravenous preparation could allow its use in neonates with seizures. Drug handling by the body is very different in neonates to adults. Before we can use levetiracetam in this age group we need to determine the correct dose and frequency by studying its absorption and distribution in the body (pharmacokinetic profile).
This study is an add-on open label pharmacokinetic and preliminary safety study. Twenty-four patients with neonatal seizures, who still experience clinical or electroencephalographic seizures after treatment with Phenobarbital will be treated with intravenous levetiracetam, and serial determinations of serum levetiracetam levels will be made to allow calculation of pharmacokinetic parameters. We will also collect preliminary safety data. We will specifically monitor for abnormalities of heart rate, respiratory rate and blood pressure, unexpected death, the occurrence of hypotonia, sedation, poor feeding, irritability or infection. Blood tests monitoring blood, liver and kidney function will be checked at baseline, 48 hours and at completion of 7 days of treatment. We will also collect preliminary descriptive data on the efficacy of levetiracetam in stopping neonatal seizures.
Study Design
Allocation: Non-Randomized, Control: Dose Comparison, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Seizures
Intervention
Intravenous levetiracetam
Location
UCSD Hillcrest Medical Center
San Diego
California
United States
92103
Status
Recruiting
Source
University of California, San Diego
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00461409
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Clonazepam
An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of GAMMA-AMINOBUTYRIC ACID receptor responses.
Seizures, Febrile
Seizures that occur during a febrile episode. It is a common condition, affecting 2-5% of children aged 3 months to five years. An autosomal dominant pattern of inheritance has been identified in some families. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy (i.e., a nonfebrile seizure disorder) following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. (From Menkes, Textbook of Child Neurology, 5th ed, p784)
Alcohol Withdrawal Seizures
A condition where seizures occur in association with ethanol abuse (ALCOHOLISM) without other identifiable causes. Seizures usually occur within the first 6-48 hours after the cessation of alcohol intake, but may occur during periods of alcohol intoxication. Single generalized tonic-clonic motor seizures are the most common subtype, however, STATUS EPILEPTICUS may occur. (Adams et al., Principles of Neurology, 6th ed, p1174)
Ethosuximide
An anticonvulsant especially useful in the treatment of absence seizures unaccompanied by other types of seizures.
Immunoglobulins, Intravenous
Immunoglobulin preparations used in intravenous infusion, containing primarily IMMUNOGLOBULIN G. They are used to treat a variety of diseases associated with decreased or abnormal immunoglobulin levels including pediatric AIDS; primary HYPERGAMMAGLOBULINEMIA; SCID; CYTOMEGALOVIRUS infections in transplant recipients, LYMPHOCYTIC LEUKEMIA, CHRONIC; Kawasaki syndrome, infection in neonates, and IDIOPATHIC THROMBOCYTOPENIC PURPURA.
Clinical Trials
Pharmacokinetic and Safety Trial of Intravenous Levetiracetam in the Treatment of Neonatal Seizures
The hypothesis is that a loading dose of 20 mg/kg and a maintenance dose of 5 mg/kg of Levetiracetam is going to be safe and effective in the treatment of seizures in neonates.
Safety Study Of Intravenous Levetiracetam
The test article for this study is levetiracetam (Keppra, which is commercially available. Keppra is indicated for use as adjunctive therapy in the treatment of partial onset seizure disor...
Prevention of Post-traumatic Seizures With Levetiracetam
Post-traumatic seizures can appear frequently after a severe traumatic brain injury. Two types of seizures are usually identified: early seizures during the week following the trauma and l...
Double-blind, randomized, placebo-controlled, multi-center clinical trial conducted to evaluate levetiracetam as adjunctive therapy in children (4-16 years) with refractory partial onset s...
An Open Label Study of Levetiracetam in Japanese Pediatric Patients With Partial Seizures
Objective of the First Period: To evaluate the efficacy of levetiracetam dry syrup at doses up to a maximum of 60 mg/kg/day or 3000 mg/day used as an adjunctive therapy in Japanese pediatr...
PubMed Articles
AIMS: The mechanisms underlying the changes in blood-brain barrier (BBB) integrity and the generation of seizures in childhood associated with preexisting brain lesions like cortical dysplasia (CD) ar...
Levetiracetam (LEV) is known to inhibit convulsive seizures and is clinically used for treating both partial and generalized seizures. The study was performed to determine whether LEV possesses an inh...
Several new antiepileptic drugs (AEDs) have been introduced for clinical use recently. These new AEDs, like the classic AEDs, target multiple cellular sites both pre- and postsynaptically. The use of...
Gaucher disease: successful treatment of myoclonic status epilepticus with levetiracetam.
We present the first reported case of a rapid clinical and electroencephalographic response to intravenous levetiracetam infusion of myoclonic status epilepticus in a patient with progressive myoclonu...
Intramuscular and intravenous levetiracetam in humans: Safety and pharmacokinetics.
A study in dogs demonstrated that the commercially available formulation of IV levetiracetam (LEV) could be given safely IM and was quickly and completely absorbed. In this crossover study, 5 women an...
