Population Pharmacokinetics of Anti-infectives in Critically Ill Children

NCT02539407 | Recruiting

• 1 other identifier: 2014-01-08
• Study Type: observational
• Target: 3,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Pediatric Intensive Care Unit; Pediatric Immuno-hematology Department

Keywords

β-lactam antibiotics; Children; Anti-infectives; Aminoglycosides, glycopeptides; Fluoroquinolone; Fungal; Antiviral

Outcome Measures

Primary Outcomes (1)

• anti-infectives concentration

  until 28 days

Secondary Outcomes (3)

• number of identified or suspected pathogen

  until 28 days

• composite measure of the health condition

  until 28 days

• predictive variables of underdosing/overdosing of antiinfectives and biological evolution

  until 28 days

Study Arms (1)

Anti-infectives

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

Other: Pharmacokinetics

Interventions

Pharmacokinetics OTHER

Anti-infectives

Eligibility Criteria

• Age: 1 Day - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Minor patients requiring the administration of anti-infectives

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Hospital Necker - Enfants Malades (Public Hospitals of Paris)

Paris, 75015, France

RECRUITING

Related Publications (8)

• 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 Nov 5;69(11):e0045125. doi: 10.1128/aac.00451-25. Epub 2025 Oct 2.

  PMID: 41036866 DERIVED

• 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.

  PMID: 39630067 DERIVED

• 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.

  PMID: 36702934 DERIVED

• 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.

  PMID: 35292609 DERIVED

• 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.

  PMID: 33318012 DERIVED

• 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.

  PMID: 32988829 DERIVED

• 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.

  PMID: 29862466 DERIVED

• 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.

  PMID: 28980166 DERIVED

MeSH Terms

Interventions

Pharmacokinetics

Intervention Hierarchy (Ancestors)

Metabolism; Pharmacological and Toxicological Phenomena; Physiological Phenomena

Study Officials

• Oualha Mehdi, MD,PhD

  Hospital Necker - Enfants Malades

  PRINCIPAL INVESTIGATOR

• Jean-Marc Treluyer, MD, PhD

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

  STUDY CHAIR

Central Study Contacts

Oualha Mehdi, MD,PhD

CONTACT

+33171196082; mehdi.oualha@nck.aphp.fr

Laure Choupeaux

CONTACT

+33 1 44 38 17 11; laure.choupeaux@aphp.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2015
• First Posted: September 3, 2015
• Study Start: September 11, 2015
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: November 20, 2025

Record last verified: 2025-10

Locations

FR (1)