Effect of Feedings on Caffeine in Premature Infants

Completed

• Conditions: Apnea of Prematurity; Premature Newborn; Caffeine
• Interventions: Drug: Caffeine

• Registration Number: NCT02293824
• Lead Sponsor: Duke University

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.

Study Timeline

• Study First Submitted: 2014-11-14
• Study First Submitted QC: 2014-11-14
• Study First Posted: 2014-11-18
• Study Start: 2014-12
• Status Verified: 2017-06
• Primary Completion: 2017-06-30
• Study Completion: 2017-06-30
• Last Update Submitted: 2017-09-11
• Last Update Posted: 2017-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Premature infants	Caffeine	Premature infants \<29 weeks birth gestational age receiving caffeine per standard of care for the prevention or treatment of apnea of prematurity.

Primary Outcome Measures

Name	Time	Method
Clearance (CL) of caffeine at steady state	Study days 0, 15, 30, 45, and 60.	Using population pharmacokinetic analyses

Secondary Outcome Measures

Name	Time	Method
Volume of distribution (V) of caffeine at steady state	Study days 0, 15, 30, 45, and 60	Using population pharmacokinetic analyses
Caffeine metabolizing enzyme activity using urinary metabolic ratios	Study days 0, 15, 30, 45, and 60	Activity levels of CYP1A2, xanthine oxidase, and N-acetyltransferase 2
Fold change in caffeine clearance due to hypoxia, hypotension, and infections	Study days 0, 15, 30, 45, and 60	Effect of hypoxia, hypotension, and infections on caffeine clearance

Trial Locations

Locations (2)

North Carolina Children's Hospital; 🇺🇸 Chapel Hill, North Carolina, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States