Population Pharmacokinetics of Anti-infectives in Critically Ill Children

NCT ID: NCT02539407

Last Updated: 2025-11-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

3000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-09-11

Study Completion Date

2028-12-31

Brief Summary

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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

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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

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Pediatric Intensive Care Unit Pediatric Immuno-hematology Department

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Anti-infectives

Anti-infectives of the following : β-lactam antibiotics, Aminoglycosides, Glycopeptides, Fluoroquinolone, Daptomycin, Rifampin, Trimethoprim, Sulfamethoxazole, Clarithromycin, Fungal, Antiviral

Pharmacokinetics

Pharmacokinetics

Intervention Type OTHER

Interventions

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Pharmacokinetics

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* Patient and parents having notified to the doctor that they refuse data recovery.
Minimum Eligible Age

1 Day

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Oualha Mehdi, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Necker - Enfants Malades

Jean-Marc Treluyer, MD, PhD

Role: STUDY_CHAIR

EA08 Paris Descartes Pharmacologie et Evaluation des thérapeutiques chez l'enfant et la femme enceinte

Locations

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Hospital Necker - Enfants Malades (Public Hospitals of Paris)

Paris, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Oualha Mehdi, MD,PhD

Role: CONTACT

+33171196082

Laure Choupeaux

Role: CONTACT

+33 1 44 38 17 11

Facility Contacts

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Oualha Mehdi, MD,PhD

Role: primary

+33171196082

References

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Berthaud R, Urien S, Krid S, Foissac F, Oualha M, Thy M, Boyer O, Beranger A, Hirt D, Benaboud S, Treluyer J-M, Bouazza N. Cefazolin population pharmacokinetics in children undergoing maintenance hemodialysis for kidney failure. Antimicrob Agents Chemother. 2025 Oct 2:e0045125. doi: 10.1128/aac.00451-25. Online ahead of print.

Reference Type DERIVED
PMID: 41036866 (View on PubMed)

Marsaux A, Leger PL, Rambaud J, Bille E, Renolleau S, Treluyer JM, Gana I, Lorrot M, Grimaud M, Toubiana J, Beranger A, Benaboud S, Oualha M. Beta-Lactam Antibiotic Exposure During Pediatric Extracorporeal Membrane Oxygenation: Retrospective Cohort Analysis of Drug Levels Using Standard Dosing, 2018-2020. Pediatr Crit Care Med. 2024 Dec 1;25(12):1127-1137. doi: 10.1097/PCC.0000000000003605. Epub 2024 Oct 7.

Reference Type DERIVED
PMID: 39630067 (View on PubMed)

Collignon C, de Marcellus C, Oualha M, Neuranter V, Heilbronner C, Hirt D. Pharmacokinetic profile of acyclovir in a child receiving continuous kidney replacement therapy for acute liver failure. Pediatr Nephrol. 2023 Oct;38(10):3493-3497. doi: 10.1007/s00467-023-05881-6. Epub 2023 Jan 27.

Reference Type DERIVED
PMID: 36702934 (View on PubMed)

de Cacqueray N, Boujaafar S, Bille E, Moulin F, Gana I, Benaboud S, Hirt D, Beranger A, Toubiana J, Renolleau S, Treluyer JM, Oualha M. Therapeutic Drug Monitoring of Antibiotics in Critically Ill Children: An Observational Study in a Pediatric Intensive Care Unit. Ther Drug Monit. 2022 Apr 1;44(2):319-327. doi: 10.1097/FTD.0000000000000918.

Reference Type DERIVED
PMID: 35292609 (View on PubMed)

Nguyen T, Oualha M, Briand C, Bendavid M, Beranger A, Benaboud S, Treluyer JM, Zheng Y, Foissac F, Winter S, Gana I, Boujaafar S, Lopez V, Berthaud R, Demir Z, Bouazza N, Hirt D. Population Pharmacokinetics of Intravenous Ganciclovir and Oral Valganciclovir in a Pediatric Population To Optimize Dosing Regimens. Antimicrob Agents Chemother. 2021 Feb 17;65(3):e02254-20. doi: 10.1128/AAC.02254-20. Print 2021 Feb 17.

Reference Type DERIVED
PMID: 33318012 (View on PubMed)

Abdalla S, Briand C, Oualha M, Bendavid M, Beranger A, Benaboud S, Treluyer JM, Zheng Y, Capito C, Demir Z, Foissac F, Winter S, Gana I, Boujaafar S, Bouazza N, Hirt D. Population Pharmacokinetics of Intravenous and Oral Acyclovir and Oral Valacyclovir in Pediatric Population To Optimize Dosing Regimens. Antimicrob Agents Chemother. 2020 Nov 17;64(12):e01426-20. doi: 10.1128/AAC.01426-20. Print 2020 Nov 17.

Reference Type DERIVED
PMID: 32988829 (View on PubMed)

Beranger A, Benaboud S, Urien S, Moulin F, Bille E, Lesage F, Zheng Y, Genuini M, Gana I, Renolleau S, Hirt D, Treluyer JM, Oualha M. Piperacillin Population Pharmacokinetics and Dosing Regimen Optimization in Critically Ill Children with Normal and Augmented Renal Clearance. Clin Pharmacokinet. 2019 Feb;58(2):223-233. doi: 10.1007/s40262-018-0682-1.

Reference Type DERIVED
PMID: 29862466 (View on PubMed)

Beranger A, Oualha M, Urien S, Genuini M, Renolleau S, Aboura R, Hirt D, Heilbronner C, Toubiana J, Treluyer JM, Benaboud S. Population Pharmacokinetic Model to Optimize Cefotaxime Dosing Regimen in Critically Ill Children. Clin Pharmacokinet. 2018 Jul;57(7):867-875. doi: 10.1007/s40262-017-0602-9.

Reference Type DERIVED
PMID: 28980166 (View on PubMed)

Other Identifiers

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2014-01-08

Identifier Type: -

Identifier Source: org_study_id

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