Clinical trial NCT02293824: Effect of Feedings on Caffeine in Premature Infants
Official title: Effect of Feedings on Caffeine Pharmacokinetics and Metabolism in Premature Infants
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Apnea of Prematurity
Premature Newborn
Caffeine
Keywords: Infant, Premature
Caffeine
Pharmacokinetics
Metabolism
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: University of North Carolina, Chapel Hill
First posted: 2014-11-18
Enrollment: 50
Sex: ALL
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Premature infants given caffeine for the prevention or treatment of apnea of prematurity.

Brief summary: Almost all infants born \<29 weeks gestational age develop apnea of prematurity and are treated with caffeine. Type of diet and disease states may be significant contributors of variability in caffeine metabolism and pharmacokinetics (PK) in this population. This prospective, observational, open-label, opportunistic PK study will compare the population PK of caffeine between infants fed formula and infants fed exclusively breast milk; compare the activities of caffeine metabolizing enzymes between infants fed formula and infants fed exclusively breast milk; and determine the effect of hypoxia, hypotension, and infection on caffeine PK and metabolism in premature infants.

Detailed description: This study will use a consecutive patient sampling approach. All eligible participants admitted at each site will be approached. Caffeine and feedings will be administered per standard of care. Manipulations of caffeine dosing or feeding regimens will not be a part of this protocol. To minimize the amount of blood sampling, the investigators will use a sparse sampling methodology. Urine will be collected for analysis of caffeine and caffeine metabolite concentrations. Caffeine pharmacokinetics will be described by population pharmacokinetic analysis. Urinary concentrations of caffeine and its metabolites will be used to calculate metabolic ratios as markers of enzyme activity.

Eligibility criteria: Inclusion Criteria:

* Written informed consent from parent(s) or legal guardian(s)
* \<29 weeks birth gestational age
* Postnatal age ≤15 days
* Receiving caffeine (intravenous or oral) per standard of care for prevention or treatment of apnea of prematurity

Exclusion Criteria:

* Known major congenital or chromosomal anomaly

Primary outcomes:
measure: Clearance (CL) of caffeine at steady state
timeFrame: Study days 0, 15, 30, 45, and 60.
Secondary outcomes:
measure: Volume of distribution (V) of caffeine at steady state
timeFrame: Study days 0, 15, 30, 45, and 60
measure: Caffeine metabolizing enzyme activity using urinary metabolic ratios
timeFrame: Study days 0, 15, 30, 45, and 60
measure: Fold change in caffeine clearance due to hypoxia, hypotension, and infections
timeFrame: Study days 0, 15, 30, 45, and 60
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: North Carolina Children's Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke Clinical Research Institute
name: Phillip B Smith, MD, MPH, MHS
role: PRINCIPAL_INVESTIGATOR
References:
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