NCT02539407

Population Pharmacokinetics of Anti-infectives in Critically Ill Children

Population Pharmacokinetics and Rationalization of Anti-infectives Administration in Critically Ill Children

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 3,000 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 1 Day – 18 Years
• Healthy volunteers: Not accepted

Summary

Concentrations and effects of anti-infectives in critically ill children are unpredictable and the risk of under-exposure may be associated with poor clinical outcomes. In addition, between-subject variability (BSV) is known to be substantial in critically ill children. Rationalisation of anti-infectives in children is therefore desirable. The investigators aim to investigate, using a population approach, the pharmacokinetics (PK) and pharmacodynamics (PD) of anti-infectives including PK/PD targets (fT(%) \> minimal inhibitory concentration (MIC)) and PD endpoints (clinical outcomes) in critically ill children. Covariates The effects of covariates on anti-infectives PK and PK/PDs are investigated in order to better explain the BSV and to ultimately suggest individualized dosage regimens. It will be a prospective PK study including 11 anti-infectives antibiotics. Six blood samples were taken from each patient during dosing interval. The primary PK/ PD targets were anti-infectives concentrations above the MIC of the pathogen at both 50% (50% f T\>MIC) and 100% (100% f T\>MIC) of the dosing interval. The investigators used skewed logistic regression to describe the effect of anti-infectives exposure on patient outcome.

Detailed description

Background and aims of the study: Recent studies have suggested a risk of under-exposure to anti-infectives in critically ill adults. This under-exposure may be associated with poor clinical outcomes as well as a delay or incomplete clinical resolution of infection; The dosing regimen of anti-infectives in critically ill children is usually based on weight (i.e. mg per Kg). However, between-subject variability is known to be substantial in children and even more so in critical illness; As a result, concentrations and effects of anti-infectives are unpredictable and the risk of under- or over-exposure is thus genuine and considerable. Rationalisation of anti-infectives in children is therefore desirable. The purpose of the present study is to investigate, using a population approach, the pharmacokinetics (PK) and pharmacodynamics (PD) of intravenous anti-infectives including usual PK/PD targets (fT(%) \> minimal inhibitory concentration (MIC)) and PD endpoints (clinical outcomes) in critically ill children. The effects of developmental and other factors related to critical illness on anti-infectives PK and PK/PDs are investigated in order to better explain the observed between-subject variabilities and to ultimately suggest individualized dosage regimens. This prospective study will be conducted in six paediatric services of Public Hospitals in Paris, France Intervention: Patient selection will take place in the 6 paediatric services. The senior physician proposes the study to holders of parental authority whose child receives or will receive anti-infectives during its follow-up or hospitalization. The senior physician will give a briefing note to the holders of parental authority, and if the child is able to understand the information. The non-oral opposition for the retrieval and analysis of data will be collected. No intervention or no charge will be made for this study.

Conditions

• Pediatric Intensive Care Unit
• Pediatric Immuno-hematology Department

Interventions

Type	Name	Description
OTHER	Pharmacokinetics

Timeline

• Start date: 2015-09-11
• Primary completion: 2028-10-01
• Completion: 2028-12-01
• First posted: 2015-09-03
• Last updated: 2025-11-20

Locations

1 site across 1 country: France