Population Pharmacokinetics of Anti-infectives in Critically Ill Children

Pediatric Intensive Care Unit Clinical Trial

— OPTIMOME  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02539407
• Other study ID #: 2014-01-08
• Status: Recruiting
• Start date: September 11, 2015
• Est. completion date: December 2028

Study information

• Verified date: October 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Oualha Mehdi, MD,PhD
• Phone: +33171196082
• Email: mehdi.oualha[@]nck.aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 3000
• Est. completion date: December 2028
• Est. primary completion date: October 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 18 Years

Eligibility

Inclusion Criteria:

• Minor patient requiring the administration of an anti-infective belonging to the following classes : ß-lactam antibiotics; aminoglycosides, glycopeptides; fluoroquinolones; other antibiotics (daptomycin, rifampin, trimethoprim, sulfamethoxazole, clarithromycin); fungal; antivirals, during its follow-up or hospitalization

Exclusion Criteria:

• Patient and parents having notified to the doctor that they refuse data recovery.

Related Conditions & MeSH terms

• Critical Illness
• Pediatric Immuno-hematology Department
• Pediatric Intensive Care Unit

Intervention

Other:
• Pharmacokinetics

Locations

Country	Name	City	State
France	Hospital Necker - Enfants Malades (Public Hospitals of Paris)	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	anti-infectives concentration		until 28 days
Secondary	number of identified or suspected pathogen		until 28 days
Secondary	composite measure of the health condition	Clinical data: anthropometric characteristics, organs function, severity score, clinical cure	until 28 days
Secondary	predictive variables of underdosing/overdosing of antiinfectives and biological evolution	Clinical data: anthropometric characteristics, organs function, severity score, clinical cure	until 28 days