Pharmacokinetics of Ampicillin in Neonates With Moderate to Severe Hypoxic-Ischemic Encephalopathy

Hypothermia Clinical Trial

Official title:

Pharmacokinetics of Ampicillin in Neonates With Moderate to Severe Hypoxic-Ischemic Encephalopathy Undergoing Controlled Hypothermia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03129620
• Other study ID #: 1301001808
• Status: Completed
• Phase: N/A
• First received: September 18, 2016
• Last updated: April 21, 2017
• Start date: March 2013
• Est. completion date: April 2016

Study information

• Verified date: April 2017
• Source: Drexel University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: April 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 24 Hours

Eligibility

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.

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Hypothermia
• Hypoxia-Ischemia, Brain

Locations

Country	Name	City	State
United States	St Christopher's Hospital for children	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Drexel University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Elevated ampicillin serum levels	Ampicillin concentration at 3 time points to determine clearance and serum levels	3 years