Population Pharmacokinetics of Anti-infectives in Critically Ill Children
- Conditions
- Pediatric Immuno-hematology DepartmentPediatric Intensive Care Unit
- Interventions
- Other: Pharmacokinetics
- Registration Number
- NCT02539407
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 3000
- Minor patient requiring the administration of an anti-infective belonging to the following classes : β-lactam antibiotics; aminoglycosides, glycopeptides; fluoroquinolones; other antibiotics (daptomycin, rifampin, trimethoprim, sulfamethoxazole, clarithromycin); fungal; antivirals, during its follow-up or hospitalization
- Patient and parents having notified to the doctor that they refuse data recovery.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Anti-infectives Pharmacokinetics Anti-infectives of the following : β-lactam antibiotics, Aminoglycosides, Glycopeptides, Fluoroquinolone, Daptomycin, Rifampin, Trimethoprim, Sulfamethoxazole, Clarithromycin, Fungal, Antiviral Pharmacokinetics
- Primary Outcome Measures
Name Time Method anti-infectives concentration until 28 days
- Secondary Outcome Measures
Name Time Method number of identified or suspected pathogen until 28 days composite measure of the health condition until 28 days Clinical data: anthropometric characteristics, organs function, severity score, clinical cure
predictive variables of underdosing/overdosing of antiinfectives and biological evolution until 28 days Clinical data: anthropometric characteristics, organs function, severity score, clinical cure
Trial Locations
- Locations (1)
Hospital Necker - Enfants Malades (Public Hospitals of Paris)
🇫🇷Paris, France