- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03248349
Population Pharmacokinetics of Antibiotics in Critically Ill Children (POPSICLE) (POPSICLE)
Population Pharmacokinetics of Antibiotics in Critically Ill Children
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Stan JF Hartman, M.D.
- Phone Number: +31622739795
- Email: Stan.Hartman@radboudumc.nl
Study Locations
-
-
Gelderland
-
Nijmegen, Gelderland, Netherlands, 6525GA
- Recruiting
- Radboudumc
-
Contact:
- Stan JF Hartman, M.D.
- Phone Number: +31622739795
- Email: Stan.Hartman@radboudumc.nl
-
Principal Investigator:
- Saskia N de Wildt, prof. M.D.
-
Sub-Investigator:
- Stan JF Hartman, M.D.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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.
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
1
Pharmacokinetics
|
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Volume of distribution of antibiotics in critically ill children
Time Frame: 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.
|
14 days
|
Clearance of antibiotics in critically ill children
Time Frame: 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.
|
14 days
|
Collaborators and Investigators
Investigators
- Principal Investigator: Saskia N de Wildt, Prof. M.D., Radboud University Medical Center
Publications and helpful links
General Publications
- Hartman SJF, Upadhyay PJ, Mathôt RAA, van der Flier M, Schreuder MF, Brüggemann 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2016-3085
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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