NCT03248349

Population Pharmacokinetics of Antibiotics in Critically Ill Children (POPSICLE)

Population Pharmacokinetics of Antibiotics in Critically Ill Children

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 200 (estimated)
• Sponsor: Radboud University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Critical Illness
• Infectious Disease
• Children

Interventions

Type	Name	Description
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

Timeline

• Start date: 2017-05-24
• Primary completion: 2020-05-01
• Completion: 2020-10-01
• First posted: 2017-08-14
• Last updated: 2020-03-13

Locations

1 site across 1 country: Netherlands

Regulatory

• FDA-regulated drug study