Clinical trial NCT05775692: Population Pharmacokinetics of Fluconazole in the Treatment of Neonatal Fungal Infectious Disease
Official title: Beijing Chilrens' Hospital
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Fluconazole
Infection
Newborn
Pharmacokinetics
Lead sponsor: Beijing Children's Hospital
Sponsor class: OTHER
Collaborators: name: Shandong University
First posted: 2023-03-20
Enrollment: 150
Sex: ALL
Minimum age (years): 1
Maximum age (years): 28
Standard ages: CHILD
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Neonates on fluconazole

Brief summary: This study is based on the hypothesis that the pharmacokinetics of fluconazole in newborns and children are different from adults. We aim to study the population pharmacokinetics of newborns and children receiving the fluconazole for treatment of infectious diseases. In this study, we will detect fluconazole concentration in plasma by using residual blood samples of blood gas analysis and other clinical tests and employ computers for constructing population pharmacokinetic models. In addition, we also want to correlate use of fluconazole with treatment effectiveness and incidence of adverse effects in newborns and children. This novel knowledge will allow better and more rational approaches to the treatment of infectious diseases in newborns and children. It will also set the foundation for further studies to improve fluconazole therapies for newborns and children.

Detailed description: 1. Establish population pharmacokinetic (PPK) models of fluconazole in newborns and children by nonlinear mixed effect modeling (NONMEM).

   At different timepoint after fluconazole administration, plasma samples of 50 newborns and children will be collected from neonatal intensive care unit (NICU) and pneumology department for fluconazole. The clinical information includes demography, medication, concentration data, blood biochemical parameters and so on .

   Plasma samples will be tested by high performance liquid chromatography (HPLC). PPK models of fluconazole will be established by NONMEM program. The reliability and stability of the PPK model will be evaluated by 1000 times of Bootstrap procedure and normalized predictive distribution error (NPDE).
2. Evaluation of the clinical feasibility and safety of individualized dosing.

According the results of PPK models, we will use dosages recommended in models to cure children infectious diseases in prospective studies. For fluconazole, 150 newborns and children will be collected.

We will compare the therapeutic effects and safety between newborns and children with conventional therapies and those with individualized therapies, including proportions of newborns and children with effective fluconazole concentration, improvement speed of of newborns and children, liver and kidney functions, adverse reactions of drugs, and so on.

Eligibility criteria: Inclusion Criteria:

Newborn （0-28d） with fluconazole against infectious diseases. The anti-infective therapy includes drugs commonly used in children infectious diseases.

Newborns infectious diseases include pneumonia, sepsis, purulent meningitis and other diseases with infection.

Informed consent signed by the parents and/or guardians.

Exclusion Criteria:

1. Allergic to any class of antibiotics;
2. Receiving other experimental drugs;
3. There are other factors that clinicians consider unsuitable for inclusion in the study.

Primary outcomes:
measure: maximum concentration (Cmax)
timeFrame: up to 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Children's Hospital of Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing Children's Hospital of Capital Medical University
name: A-Dong Shen, Master
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhao W, Lopez E, Biran V, Durrmeyer X, Fakhoury M, Jacqz-Aigrain E. Vancomycin continuous infusion in neonates: dosing optimisation and therapeutic drug monitoring. Arch Dis Child. 2013 Jun;98(6):449-53. doi: 10.1136/archdischild-2012-302765. Epub 2012 Dec 19.
citation: Leroux S, Zhao W, Betremieux P, Pladys P, Saliba E, Jacqz-Aigrain E; French Society of Neonatology. Therapeutic guidelines for prescribing antibiotics in neonates should be evidence-based: a French national survey. Arch Dis Child. 2015 Apr;100(4):394-8. doi: 10.1136/archdischild-2014-306873. Epub 2015 Jan 27.
citation: Jacqz-Aigrain E, Leroux S, Zhao W, van den Anker JN, Sharland M. How to use vancomycin optimally in neonates: remaining questions. Expert Rev Clin Pharmacol. 2015;8(5):635-48. doi: 10.1586/17512433.2015.1060124. Epub 2015 Aug 4.