Population Pharmacokinetics of Antibiotics in Critically Ill Children (POPSICLE)

• Conditions: Critical Illness; Infectious Disease; Children
• Interventions: Drug: Pharmacokinetics

• Registration Number: NCT03248349
• Lead Sponsor: Radboud University Medical Center

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2017-05-24
• Study First Submitted: 2017-08-02
• Study First Submitted QC: 2017-08-09
• Study First Posted: 2017-08-14
• Status Verified: 2019-09
• Last Update Submitted: 2020-03-12
• Last Update Posted: 2020-03-13
• Primary Completion: 2020-05-01
• Study Completion: 2020-10-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 200

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).

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Exclusion Criteria

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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
1	Pharmacokinetics	Pharmacokinetics

Primary Outcome Measures

Name	Time	Method
Volume of distribution of antibiotics in critically ill children	14 days	Population mean value of volume of distribution of antibiotics during critical illness. Mean population volume of distribution will be derived from pooled data of antibiotic concentrations. Covariates of influence on volume of distribution will be incorporated within a population pharmacokinetic model.
Clearance of antibiotics in critically ill children	14 days	Population mean value of clearance of antibiotics during critical illness. Mean population clearance will be derived from pooled data of antibiotic concentrations. Covariates of influence on drug clearance will be incorporated within a population pharmacokinetic model.

Trial Locations

Locations (1)

Radboudumc; 🇳🇱 Nijmegen, Gelderland, Netherlands