Objective: Primary objective: safety profile of LEV in neonates. Safety outcome parameters as liver, kidney and metabolic function, electrolytes, hemodynamic effects (heart rate/arrhythmia, arterial blood pressure/hypotension). Investigation of…
ID
Source
Brief title
Condition
- Seizures (incl subtypes)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety profile of LEV in neonates. Outcome parameters as liver-, kidney- and
metabolic function, electrolytes, hemodynamic effects (heart rate/arrythmias,
arterial bloodpressure/hypotension). Investigation of pharmacokinetic and -
dynamic properties of LEV at neonates.
Secondary outcome
Increase of epileptic seizures and medication interaction will be measured.
Background summary
Background: Both clinical and laboratory studies demonstrate that neonatal
seizures can cause cognitive, behavioural or epileptic complications later in
life. Therefore, treatment is needed. On the other hand, commonly used
anticonvulsants can have a harmful effect on the developing brain. A mild
safety profile, a different antiseizure mechanism and indications for
neuroprotective properties make levetiracetam (LEV) (Keppra®) interesting for
the use in neonates.
Hypothesis: The use of parenterally administered LEV in neonatal epileptic
seizures, detected electrographically, with or without clinical signs, will be
safe.
Study objective
Objective: Primary objective: safety profile of LEV in neonates. Safety outcome
parameters as liver, kidney and metabolic function, electrolytes, hemodynamic
effects (heart rate/arrhythmia, arterial blood pressure/hypotension).
Investigation of pharmacokinetic and -dynamic properties of LEV in neonates.
Secondary objective: Increase of epileptic activity and drug interaction will
be determined or registered.
Study design
Open label pilot study.
Intervention
Levetiracetam intravenously as a second or third line anticonvulsant, 20 mg/kg;
in the absence of a response after 10 min. a second dose of 20 mg/kg will be
given.
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: As all patients with (increased risk for)
neonatal seizures EEG electrodes will be applied. All patients admitted to the
NICU will receive an arterial catheter. Blood samples will be taken from the
arterial catheter. Fifteen samples of 0.3 ml in the first 72 hours after
inclusion will be drawn for LEV plasma concentrations. Three samples of 0.5 ml
will be drawn for liver- and kidney functions and electrolytes.
Known side-effects in children and adults are dizziness, somnolence, fatigue,
behavioral disturbances. There are no effects on respiratory or kidney
function. An increase in heart rate and arterial blood pressure was seen in
dogs after a dose 10-fold the human used dose. In human studies no
cardiovascular side-effects were seen. In conclusion, this safety study is
needed to determine the possible side-effects in neonates, but in older
patients the side-effects are minimal, and the burden regarding the procedures
is minimal.
Dr. Molewaterplein 60
3015 GJ Rotterdam
NL
Dr. Molewaterplein 60
3015 GJ Rotterdam
NL
Listed location countries
Age
Inclusion criteria
·newborn gestational age >= 37 weeks, birth weight > 1500 grams
·refractory to phenobarbitone up to 40 mg/kg or refractory to phenobarbitone up to 40 mg/kg and midazolam up to 0.5 mg/kg (raised from 0.1 mg/kg every 10-15 minutes when effect fails)
·after correction or treatment of metabolic causes as inborn errors, hypoglycemia or hypocalcaemia or CNS infections
Exclusion criteria
·newborn gestational age < 37 weeks, birth weight < 1500 grams
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-006804-12-NL |
| CCMO | NL15182.078.06 |