Clinical trial NCT00797420: Pharmacokinetics (PK) Study of a Fluconazole Loading Dose in Infants and Toddlers
Official title: Pharmacokinetics of a Fluconazole Loading Dose in Infants and Toddlers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Candidiasis
Keywords: fluconazole
pharmacokinetic
candidiasis
sepsis
pediatric
infants
antifungal
candidemia
fungemia
loading dose
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Pediatric Pharmacology Research Units Network
First posted: 2008-11-25
Enrollment: 13
Sex: ALL
Minimum age (years): 48
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the pharmacokinetics and safety of a fluconazole loading dose in infants and toddlers.

Detailed description: This is an open label study to investigative the pharmacokinetics and safety of a fluconazole loading dose in infants and toddlers \< 2 years of age with suspected sepsis. There will be two treatment groups: single fluconazole loading dose 25 mg/kg; fluconazole loading dose 25mg/kg followed by 12 mg/kg daily for total of 5 days. There will be three age cohorts within each group: pre-term \< 30 week EGA infants \> 48 hours and \< 31 days; \> 30 weeks EGA infants \> 48 hours and \< 31 days; infants ≥ 31 days and \< 2 years of age. The study requires administration of fluconazole over 1-5 days depending on treatment group followed by 1 week of safety monitoring. Six to eight 100 µL PK samples will be obtained over the 5 days of drug administration. The risks are reasonable vs. the benefits and have been minimized appropriately. There may be benefit to the subjects (administration of empirical antifungal therapy), and information from the study may benefit a large number of other infants and toddlers with suspected or proven fungal sepsis. There is a data analysis plan.

Eligibility criteria: Inclusion Criteria:

* suspected sepsis with blood culture within 48 hours
* age ≥ 48 hours and \< 2 years of age
* sufficient venous access to permit study drug administration

Exclusion Criteria:

* allergic reaction to azole
* history of fluconazole administration in prior 5 days
* liver dysfunction
* renal failure
* concomitant use of cyclosporine, tacrolimus, or azithromycin

Primary outcomes:
measure: Plasma concentration of Fluconazole
timeFrame: 6-8 samples over 5 days
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Univeristy Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Daniel Benjamin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Benjamin DK Jr, Stoll BJ. Infection in late preterm infants. Clin Perinatol. 2006 Dec;33(4):871-82; abstract x. doi: 10.1016/j.clp.2006.09.005.
citation: Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, Oh W, Bauer CR, Korones SB, Shankaran S, Laptook AR, Stevenson DK, Papile LA, Poole WK. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics. 2002 Aug;110(2 Pt 1):285-91. doi: 10.1542/peds.110.2.285.
citation: Benjamin DK Jr, DeLong ER, Steinbach WJ, Cotton CM, Walsh TJ, Clark RH. Empirical therapy for neonatal candidemia in very low birth weight infants. Pediatrics. 2003 Sep;112(3 Pt 1):543-7. doi: 10.1542/peds.112.3.543.
citation: Novelli V, Holzel H. Safety and tolerability of fluconazole in children. Antimicrob Agents Chemother. 1999 Aug;43(8):1955-60. doi: 10.1128/AAC.43.8.1955.
citation: Brammer KW, Coates PE. Pharmacokinetics of fluconazole in pediatric patients. Eur J Clin Microbiol Infect Dis. 1994 Apr;13(4):325-9. doi: 10.1007/BF01974613.
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.
citation: Anaissie EJ, Kontoyiannis DP, Huls C, Vartivarian SE, Karl C, Prince RA, Bosso J, Bodey GP. Safety, plasma concentrations, and efficacy of high-dose fluconazole in invasive mold infections. J Infect Dis. 1995 Aug;172(2):599-602. doi: 10.1093/infdis/172.2.599.