Population Pharmacokinetics of Antibiotics in Critically Ill Children (POPSICLE)

Critical Illness Clinical Trial

— POPSICLE  

Official title:

Population Pharmacokinetics of Antibiotics in Critically Ill Children

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03248349
• Other study ID #: 2016-3085
• Status: Recruiting
• Start date: May 24, 2017
• Est. completion date: October 1, 2020

Study information

• Verified date: September 2019
• Source: Radboud University
• Contact: Stan JF Hartman, M.D.
• Phone: +31622739795
• Email: Stan.Hartman[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: October 1, 2020
• Est. primary completion date: May 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Children
• Communicable Diseases
• Critical Illness
• Infection
• Infectious Disease

Intervention

Drug:
• Pharmacokinetics
Blood samples are drawn for pharmacokinetic properties of antibiotics during routine care treatment Blood samples for relevant covariates of drug disposition (kidney function, liver enzymes, C-reactive protein (CRP), albumin) Whole blood is stored for DNA analysis Urine is drawn from catheter for more detailed estimation of glomerular filtration rate and drug metabolite analysis

Locations

Country	Name	City	State
Netherlands	Radboudumc	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Volume of distribution of antibiotics in critically ill children	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
Primary	Clearance of antibiotics in critically ill children	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