Clinical trial NCT03129620: Pharmacokinetics of Ampicillin in Neonates With Moderate to Severe Hypoxic-Ischemic Encephalopathy
Official title: Pharmacokinetics of Ampicillin in Neonates With Moderate to Severe Hypoxic-Ischemic Encephalopathy Undergoing Controlled Hypothermia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hypothermia
Keywords: Ampicillin
Lead sponsor: Drexel University
Sponsor class: OTHER
First posted: 2017-04-26
Enrollment: 14
Sex: ALL
Minimum age (years): 6
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Neonates 0-24 hours of life

Brief summary: Controlled Hypothermia has become the standard of care for neonates with moderate to severe HIE. Ampicillin and aminoglycosides are drugs that are universally used for the treatment of suspected neonatal sepsis, which may or may not be responsible for the etiology of HIE. Currently, medication dosage regimens are not altered in the setting of CH. A better understanding of the effects of our interventions on this unique population may help us tailor our therapy to the specific circumstances of the patient

Detailed description: Hypoxic-ischemic encephalopathy (HIE) affects approximately 1 to 2 per 1000 live births and remains a cause of significant morbidity and mortality in the neonatal period. In response to an anoxic insult, perfusion to vital organs is preserved; however, when this injury is profound concomitant injury to nonvital organs is observed. Controlled hypothermia (CH) has been accepted as a neuroprotective therapeutic modality for neonates with moderate to severe HIE because of its role in attenuating secondary brain injury. Neonates exhibit varying degrees of multiorgan dysfunction after a hypoxic-ischemic insult, although the added beneficial and potential adverse effects that CH has in these babies have not been completely delineated or understood.

CH has been shown to alter normal physiologic functioning of several organ systems. Specific physiologic changes as a consequence of CH have been demonstrated in both animal and human models. The observed reduction in cardiac output and reflexive increase in systemic vascular resistance in response to CH alter renal perfusion and subsequently reduce glomerular filtration . Drugs that are renally cleared may develop a prolonged half-life in this setting. Finally, drug metabolism may further be affected by altered hepatic blood flow and temperature-dependent effects on hepatic enzyme activity . Collectively, the potential effects of CH on drug metabolism and clearance are significant warranting further investigation. The investigator aims to evaluate the combined effects of hypoxia and hypothermia on ampicillin clearance and excretion

Eligibility criteria: Inclusion Criteria:

* Gestational age \> 36 weeks
* Birth weight \> 1800 grams
* Age \< 6 hours old at the time of admission to the NICU
* Cord gas or ABG/VBG with pH \< 7.0 or base deficit \> 16 within the first hour of life
* Presence of seizures or evidence of moderate to severe encephalopathy
* Presence of central line for lab draws

Exclusion Criteria:

• Infants admitted for CH without central intravascular access.

Primary outcomes:
measure: Elevated ampicillin serum levels
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: St Christopher's Hospital for children
state: Pennsylvania
Study officials:
References: