Clinical trial NCT03248349: Population Pharmacokinetics of Antibiotics in Critically Ill Children (POPSICLE)
Official title: Population Pharmacokinetics of Antibiotics in Critically Ill Children
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Critical Illness
Infectious Disease
Children
Keywords: Critically ill children
Pharmacokinetics
Anti-Bacterial agents
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2017-08-14
Enrollment: 200
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Critically ill children receiving antibiotics.

Brief summary: Infections are common on the Intensive Care for both adult and pediatric patients. Adequately dosing antibiotic treatment is of vital importance but both under- and overdosing is frequent due to pathophysiological changes during critical illness. Moreover, the interplay of age and critical illness is even more understudied.

To optimize antibiotic dosing and outcome of infectious disease, personalized dosing guidelines in critically ill patients are highly needed. In this prospective observational population pharmacokinetic study we will evaluate if target attainment for antibiotics is reached in critically ill children with current dosing guidelines. Using these data, individualized dosing guidelines will be developed.

Detailed description: Approximately one third of all critically ill children develop infectious disease related complications. Mortality due to infections can be as high as 30-45%. In up to 41% of adult critically ill patients antimicrobial dosing recommendations are inadequate, as acute kidney injury, augmented renal clearance, inflammatory response and hypoalbuminaemia all contribute to variation in drug concentrations. This is an important reason for antibiotic treatment failure and emergence of resistance.

Data from adults cannot be directly extrapolated to children, due to developmental changes in the processes involved in drug disposition. Moreover, the interplay of age and critical illness is even more understudied. Hence, to optimize antibiotic dosing and outcome of infectious disease, personalized dosing guidelines in critically ill patients are highly needed.

In this prospective observational population pharmacokinetic study we will evaluate if target attainment for antibiotics is reached in critically ill children with current dosing guidelines. Using these data, individualized dosing guidelines will be developed.

Objectives:

To determine the population pharmacokinetics of antibiotics in critically ill pediatric patients to develop individualized dosing guidelines for antibiotics for this population.

Study design:

Observational study with minimal invasive procedures: population pharmacokinetic study.

Study population:

Critically ill children, admitted on the pediatric intensive care unit (PICU), receiving antibiotics.

Study parameters/endpoints:

Primary:

* To estimate population pharmacokinetic parameters for antibiotics

Secondary:

* To determine the target attainment rate of antibiotic exposure
* To design individualized dosing guidelines for antibiotics

Exploratory:

* To describe variability in kidney function
* To explore the relationship of genetic variation with disposition of pharmacokinetics.

Eligibility criteria: Inclusion Criteria:

* 0 to 18 years of postnatal age;
* \>37 weeks of gestational age (in children less than 6 months of postnatal age);
* Admitted to pediatric intensive care unit;
* Indwelling central line or arterial line in place for clinical purposes, or regular blood work for clinical reasons;
* Antibiotic therapy already prescribed by treating physician;
* Written informed consent (IC).

Exclusion Criteria:

* Language or cognitive inability to understand written and oral informed consent.

Primary outcomes:
measure: Volume of distribution of antibiotics in critically ill children
timeFrame: 14 days
measure: Clearance of antibiotics in critically ill children
timeFrame: 14 days
Secondary outcomes:
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: Saskia N de Wildt, Prof. M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hartman SJF, Upadhyay PJ, Mathot RAA, van der Flier M, Schreuder MF, Bruggemann RJ, Knibbe CA, de Wildt SN. Population pharmacokinetics of intravenous cefotaxime indicates that higher doses are required for critically ill children. J Antimicrob Chemother. 2022 May 29;77(6):1725-1732. doi: 10.1093/jac/dkac095.
citation: Hartman SJF, Upadhyay PJ, Hagedoorn NN, Mathot RAA, Moll HA, van der Flier M, Schreuder MF, Bruggemann RJ, Knibbe CA, de Wildt SN. Current Ceftriaxone Dose Recommendations are Adequate for Most Critically Ill Children: Results of a Population Pharmacokinetic Modeling and Simulation Study. Clin Pharmacokinet. 2021 Oct;60(10):1361-1372. doi: 10.1007/s40262-021-01035-9. Epub 2021 May 26.