This study has been transitioned to CTIS with ID 2024-518305-17-01 check the CTIS register for the current data. Primary objective:• To establish an improved fluconazole dosing regimen for paediatric and adolescent patients aged 2-18 years.…
ID
Source
Brief title
Condition
- Fungal infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary study parameters/endpoints:
Since the primary objective of this study is to establish an improved
fluconazole dosing regimen for paediatric and adolescent patients aged 2-18
years, we aim to describe fluconazole pharmacokinetics in this patient
population by means of population pharmacokinetic (pop-PK) modelling. The
pharmacokinetic parameters of the developed pop-PK model are among others,
clearance (CL), volume of distribution (Vd) and exposure described by the area
under the concentration-time curve (AUC). With the developed model, simulations
will be performed to estimate the percentage of patients reaching the
predefined PK target of AUC above 400 mg*h/L. We subsequently aim to establish
an improved fluconazole dosing regimen for the studied population which will
consist of a loading dose and a maintenance dose that will result in adequate
fluconazole exposure in these patients.
Secondary outcome
Other study parameters are factors that might influence the primary study
parameters, the covariates. Since this is an observational study, potential
covariates will only be explored. Covariates of interest are renal clearance
and body weight. Another study parameter that will be explored is the oral
bioavailability (F) of fluconazole, which is the percentage of the drug that is
systemically available after oral administration compared to the exposure after
intravenous administration.
Background summary
Fluconazole has been available since 1990, however a limited number of studies
addressed the pharmacokinetics of fluconazole in children and adolescent
patients. Solid PK data are lacking, despite there being expected variation due
to physiological differences with adults likely resulting in significant
clinical impact. Especially in the paediatric population where fluconazole is
extensively used, including in patients who have moderate to severe renal
function disturbances, this information is needed. Therefore, it seems prudent
to conduct a study in a cohort of paediatric patients who receive fluconazole
as prophylaxis or treatment.
Study objective
This study has been transitioned to CTIS with ID 2024-518305-17-01 check the CTIS register for the current data.
Primary objective:
• To establish an improved fluconazole dosing regimen for paediatric and
adolescent patients aged 2-18 years.
Exploratory objectives:
• To explore the role of renal function on the clearance of fluconazole.
• To explore the bioavailability of oral fluconazole versus intravenous
fluconazole in paediatric patients.
Study design
Prospective, observational pharmacokinetic study
Study burden and risks
Patients are treated according to standard care. No changes to fluconazole
therapy are made for the purpose of this study. Patients are treated to the
discretion of the treating physician. Therefore, no additional risks are
expected compared to the standard risks expected with the use of fluconazole.
The collection of a minimal amount of extra blood (maximal amount of 12 ml for
all patients, and maximal amount of 18 ml for patients with an extra PK-day due
to switching from oral to iv therapy) from an already indwelling arterial line
or CVC before the start of the study will result in a minimal risk for of
clotting or infection in the line. This risk is reduced to a minimum.
Because the goal of the study is to describe the PK of fluconazole in children
with the aim of establishing an improved dosing regimen, it is of importance to
collect data from a population that resembles the real-life population. This
real-life population consists for a large part of patients admitted to the IC,
which sometimes are unconscious and therefore incapacitated.
Geert Grooteplein Zuid 30
Nijmegen 6500HB
NL
Geert Grooteplein Zuid 30
Nijmegen 6500HB
NL
Listed location countries
Age
Inclusion criteria
1. Subject is treated with fluconazole for prophylaxis or treatment of an
invasive fungal infection;
2. Subject is 2 - 18 years of age on the day of the first fluconazole dosing;
3. Subject is managed with a central venous catheter or arterial line from
which blood can be easily obtained.
Exclusion criteria
1. Subject is managed by means of an extracorporeal clearance technique;
2. Subject has previously participated in this study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-518305-17-01 |
| EudraCT | EUCTR2021-006868-24-NL |
| ClinicalTrials.gov | NCT05130723 |
| CCMO | NL80071.091.22 |