Levetiracetam Treatment of Neonatal Seizures: Safety and Efficacy Phase II Study (LEVNEONAT-1)

Regional University Hospital Center (CHRU)

Status and phase: Completed; Phase 2

Conditions: Neonatal Seizures

Treatments: Drug: Intravenous Levetiracetam

Study type: Interventional

Funder types: Other

Identifiers

NCT02229123

2014-000791-26

Details and patient eligibility

About

LEVNEONAT is a multicentre French clinical trials with the aim to develop new treatment strategies for the treatment of neonatal seizures using Levetiracetam. The purpose of this study is to determine the correct dosing, safety and efficacy for intravenous levetiracetam as first line treatment in term newborn babies with seizures in hypoxic-ischemic encephalopathy context. This new anticonvulsivant drug is a promising treatment for seizures in newborns.

Full description

Article Focus

• The principal aim of LEVNEONAT-1 is to determine the levetiracetam optimal dose defined as the highest efficient dose under toxicity restrictions for treating neonatal seizures.
• LEVNEONAT-1 is an open-label, sequential dose-finding study with 3 increasing dose levels of levetiracetam.

Strenghts and limitation of study

• For the first time, levetiracetam will be used as the first-line treatment of neonatal seizures and not as an add-on therapy.
• Statistical model is designed for a rare clinical situation with a sequential adaptive method updating in real time the dose allocation for next patient by using all available data from previous participants.
• The targeted population, i.e. the newborn less than 3 days of life, is particularly sensitive and the written consent of both parents is required before the levetiracetam administration.

Enrollment: 18 patients

Sex: All

Ages: 36 to 43 weeks old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Eligibility Criteria:

1. Male or female term baby with gestational age of 36-43 weeks and postnatal age < or= 72 hours

2. One or more of the following :

   • APGAR score < 5 at 5 mins
   • Umbilical cord or arterial blood sample (within one hour after birth): pH <7.0 or base deficit > or = 16 mmol/L or lactates > or equal to 11 mmol/L
   • Abnormal neurological examination before 6 hours of life

3. Suspected clinical or EEG seizures

Inclusion criteria:

• A seizure lasting more than 3 minutes or more than 2 seizures lasting more than 20 seconds on a 1 hour-period on standard EEG recording 4 hours before the levetiracetam loading dose
• Availability of 8 electrode EEG recording
• Written informed consent of both parents or the authorized guardians
• Subscription to social security health insurance are required

Exclusion Criteria:

• Suspected or confirmed brain malformation, inborn error of metabolism, genetic syndrome or major congenital malformation
• Congenital (in utero) infection (TORCH)
• Babies who have received phenobarbital or any other anticonvulsive medication other than a bolus of midazolam for intubation
• Anuria/renal failure defined as serum creatinine > 150 micromol/L
• Seizures secondary to treatable metabolic etiology as hypoglycemia and hypocalcemia
• Corrected QT interval (QTc) greater than 450 milliseconds on the electrocardiogram (ECG) prior to inclusion in the presence or absence of a condition that promotes QT prolongation (hypokalemia, maternal treatment during childbirth or treatment of the child with drugs known to prolong QT),
• Participation to an interventional research study

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

18 participants in 1 patient group

Intravenous levetiracetam

Experimental group

Description:

1 loading dose of 30, 40 or 50 mg/kg administered intra-venously. Maintenance treatment: one intra-venous injection /8h, 8 doses in total for a 3-day treatment. Maintenance dose corresponds to the loading dose quarter i.e. 7.5, 10 or 12.5 mg/kg.

Treatment:

Drug: Intravenous Levetiracetam