NCT02293824

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Dec 2014

Typical duration for all trials

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 14, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

November 18, 2014

Completed
13 days until next milestone

Study Start

First participant enrolled

December 1, 2014

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2017

Completed
Last Updated

September 13, 2017

Status Verified

June 1, 2017

Enrollment Period

2.6 years

First QC Date

November 14, 2014

Last Update Submit

September 11, 2017

Conditions

Apnea of PrematurityPremature NewbornCaffeine

Keywords

Infant, PrematureCaffeinePharmacokineticsMetabolism

Outcome Measures

Primary Outcomes (1)

  • Clearance (CL) of caffeine at steady state

    Using population pharmacokinetic analyses

    Study days 0, 15, 30, 45, and 60.

Secondary Outcomes (3)

  • Volume of distribution (V) of caffeine at steady state

    Study days 0, 15, 30, 45, and 60

  • Caffeine metabolizing enzyme activity using urinary metabolic ratios

    Study days 0, 15, 30, 45, and 60

  • Fold change in caffeine clearance due to hypoxia, hypotension, and infections

    Study days 0, 15, 30, 45, and 60

Study Arms (1)

Premature infants

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

Drug: Caffeine

Interventions

CaffeineDRUG

Given per standard of care.

Also known as: Caffeine Citrate, Cafcit
Premature infants

Eligibility Criteria

AgeUp to 15 Days
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)
Sampling MethodProbability Sample
Study Population

Premature infants given caffeine for the prevention or treatment of apnea of prematurity.

You may qualify if:

  • 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

You may not qualify if:

  • Known major congenital or chromosomal anomaly

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

North Carolina Children's Hospital

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (10)

  • Zhao J, Gonzalez F, Mu D. Apnea of prematurity: from cause to treatment. Eur J Pediatr. 2011 Sep;170(9):1097-105. doi: 10.1007/s00431-011-1409-6. Epub 2011 Feb 8.

    PMID: 21301866BACKGROUND

  • Di Fiore JM, Bloom JN, Orge F, Schutt A, Schluchter M, Cheruvu VK, Walsh M, Finer N, Martin RJ. A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity. J Pediatr. 2010 Jul;157(1):69-73. doi: 10.1016/j.jpeds.2010.01.046. Epub 2010 Mar 20.

    PMID: 20304417BACKGROUND

  • Janvier A, Khairy M, Kokkotis A, Cormier C, Messmer D, Barrington KJ. Apnea is associated with neurodevelopmental impairment in very low birth weight infants. J Perinatol. 2004 Dec;24(12):763-8. doi: 10.1038/sj.jp.7211182.

    PMID: 15329741BACKGROUND

  • Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Reported medication use in the neonatal intensive care unit: data from a large national data set. Pediatrics. 2006 Jun;117(6):1979-87. doi: 10.1542/peds.2005-1707.

    PMID: 16740839BACKGROUND

  • Gal P. Caffeine Therapeutic Drug Monitoring Is Necessary and Cost-effective. J Pediatr Pharmacol Ther. 2007 Oct;12(4):212-5. doi: 10.5863/1551-6776-12.4.212. No abstract available.

    PMID: 23055855BACKGROUND

  • Blake MJ, Abdel-Rahman SM, Pearce RE, Leeder JS, Kearns GL. Effect of diet on the development of drug metabolism by cytochrome P-450 enzymes in healthy infants. Pediatr Res. 2006 Dec;60(6):717-23. doi: 10.1203/01.pdr.0000245909.74166.00. Epub 2006 Oct 25.

    PMID: 17065585BACKGROUND

  • Le Guennec JC, Billon B. Delay in caffeine elimination in breast-fed infants. Pediatrics. 1987 Feb;79(2):264-8.

    PMID: 3808800BACKGROUND

  • Xu H, Rajesan R, Harper P, Kim RB, Lonnerdal B, Yang M, Uematsu S, Hutson J, Watson-MacDonell J, Ito S. Induction of cytochrome P450 1A by cow milk-based formula: a comparative study between human milk and formula. Br J Pharmacol. 2005 Sep;146(2):296-305. doi: 10.1038/sj.bjp.0706319.

    PMID: 15997229BACKGROUND

  • Supnet MC, David-Cu R, Walther FJ. Plasma xanthine oxidase activity and lipid hydroperoxide levels in preterm infants. Pediatr Res. 1994 Sep;36(3):283-7. doi: 10.1203/00006450-199409000-00003.

    PMID: 7808822BACKGROUND

  • Hassoun PM, Yu FS, Cote CG, Zulueta JJ, Sawhney R, Skinner KA, Skinner HB, Parks DA, Lanzillo JJ. Upregulation of xanthine oxidase by lipopolysaccharide, interleukin-1, and hypoxia. Role in acute lung injury. Am J Respir Crit Care Med. 1998 Jul;158(1):299-305. doi: 10.1164/ajrccm.158.1.9709116.

    PMID: 9655743BACKGROUND

Related Links

MeSH Terms

Conditions

ApneaPremature Birth

Interventions

Caffeinecaffeine citrate

Condition Hierarchy (Ancestors)

Respiration DisordersRespiratory Tract DiseasesSigns and Symptoms, RespiratorySigns and SymptomsPathological Conditions, Signs and SymptomsObstetric Labor, PrematureObstetric Labor ComplicationsPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital Diseases

Intervention Hierarchy (Ancestors)

XanthinesAlkaloidsHeterocyclic CompoundsPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Phillip B Smith, MD, MPH, MHS

    Duke Clinical Research Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 14, 2014

First Posted

November 18, 2014

Study Start

December 1, 2014

Primary Completion

June 30, 2017

Study Completion

June 30, 2017

Last Updated

September 13, 2017

Record last verified: 2017-06

Locations

US(2)