Clinical trial NCT00514358: Fluconazole Pharmacokinetics in Infants
Official title: A Multicenter, Open Label Pharmacokinetic Study of Fluconazole in Infants
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Fungal Infection
Keywords: Fungal
Infection
sepsis
pharmacokinetics
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Pediatric Pharmacology Research Units Network
First posted: 2007-08-09
Enrollment: 55
Sex: ALL
Maximum age (years): 119
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Premature and term infants less than 90 days of age who are receiving fluconazole as standard of care therapy.

Brief summary: The purpose of this study is to determine the pharmacokinetics of fluconazole in infants and evaluate the dose exposure relationship of current fluconazole dosing in infants who are receiving fluconazole for the prevention or treatment of systemic fungal infections.

Detailed description: Systemic fungal infections in neonates are associated with high morbidity and mortality. The increasing use of intravenous central catheters, parenteral nutrition, and antibiotics in neonatal intensive care units has contributed not only to improved survival but also to the increasing incidence of fungal sepsis particularly in preterm infants. Decreasing fungal colonization can decrease the risk of systemic fungal infection. Fluconazole is a potent antifungal agent in the triazole family. Fluconazole has been shown to reduce the risk of fungal colonization and systemic infection however we do not have sufficient pharmacokinetic information in neonates to support dosing guidelines. In this study, we will perform a population pharmacokinetic study in neonates receiving fluconazole as standard of care. Fluconazole levels will be measured using a liquid chromatography/tandem mass spectroscopy (LC/MS/MS) assay from very small quantities of blood appropriate for neonates. Pharmacokinetic data obtained in this study will support appropriate dosing of fluconazole in neonates and provide information regarding drug metabolism in neonates.

Eligibility criteria: Inclusion Criteria:

1. Infant born \>23 weeks gestational age with postnatal age \<120 days
2. Due to receive fluconazole therapy for clinical care
3. Permission from attending neonatologist
4. Informed consent of parent or legal guardian

Primary outcomes:
measure: To develop a population PK model of fluconazole drug disposition in premature infants who are receiving fluconazole for treatment or prophylaxis against systemic fungal infections.
timeFrame: 3 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Children's Hospital of Michigan, Wayne State University
state: Michigan
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital, Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Kelly C. Wade, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Peter C Adamson, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Jeffery Barrett, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wade KC, Benjamin DK Jr, Kaufman DA, Ward RM, Smith PB, Jayaraman B, Adamson PC, Gastonguay MR, Barrett JS. Fluconazole dosing for the prevention or treatment of invasive candidiasis in young infants. Pediatr Infect Dis J. 2009 Aug;28(8):717-23. doi: 10.1097/INF.0b013e31819f1f50.
citation: Wade KC, Wu D, Kaufman DA, Ward RM, Benjamin DK Jr, Sullivan JE, Ramey N, Jayaraman B, Hoppu K, Adamson PC, Gastonguay MR, Barrett JS; National Institute of Child Health and Development Pediatric Pharmacology Research Unit Network. Population pharmacokinetics of fluconazole in young infants. Antimicrob Agents Chemother. 2008 Nov;52(11):4043-9. doi: 10.1128/AAC.00569-08. Epub 2008 Sep 22.