Pediatric Intensive Care UnitOPTIMOMENCT02539407
Population Pharmacokinetics of Anti-infectives in Critically Ill Children
An observational study of Pediatric Intensive Care Unit and Pediatric Immuno-hematology Department, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 1 day to 18 years
- Conditions the study is for
- Pediatric Intensive Care Unit, Pediatric Immuno-hematology Department
- What is being tested?
- Pharmacokinetics
- How many people
- 3,000 participants
- Where
- 1 siteFrance
- Study dates
- 11 Sep 2015to Dec 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Minor patients requiring the administration of anti-infectives
Who may be able to join
- 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
Who cannot join
- Patient and parents having notified to the doctor that they refuse data recovery.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Hospital Necker - Enfants Malades (Public Hospitals of Paris)
Paris, 75015
Oualha Mehdi, MD,PhD, +33171196082
About this study
Official title: Population Pharmacokinetics and Rationalization of Anti-infectives Administration in Critically Ill Children
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.
Read the 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.
- Being tested
- Pharmacokinetics
- Keywords
- β-lactam antibiotics, Children, Anti-infectives, Aminoglycosides, glycopeptides, Fluoroquinolone, Fungal, Antiviral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PharmacokineticsOther
| Study group | Role | What they receive |
|---|---|---|
| Anti-infectives | Anti-infectives of the following : β-lactam antibiotics, Aminoglycosides, Glycopeptides, Fluoroquinolone, Daptomycin, Rifampin, Trimethoprim, Sulfamethoxazole, Clarithromycin, Fungal, Antiviral
Pharmacokinetics Receives: Other: Pharmacokinetics |
What is being measured
The primary outcome is the main question the study is designed to answer.
anti-infectives concentration
Measured: until 28 days
Secondary outcomes (3)
number of identified or suspected pathogen
Measured: until 28 days
composite measure of the health condition
Clinical data: anthropometric characteristics, organs function, severity score, clinical cure
Measured: until 28 days
predictive variables of underdosing/overdosing of antiinfectives and biological evolution
Clinical data: anthropometric characteristics, organs function, severity score, clinical cure
Measured: until 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2015 (estimated)
- Study start11 Sep 2015
- Primary completionOct 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Pediatric Intensive Care UnitStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 3,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Oualha Mehdi, MD,PhD, Principal investigator, Hospital Necker - Enfants MaladesJean-Marc Treluyer, MD, PhD, Study chair, EA08 Paris Descartes Pharmacologie et Evaluation des thérapeutiques chez l'enfant et la femme enceinte
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02539407
- Sponsor's protocol ID
- 2014-01-08
- Acronym
- OPTIMOME
- Status last verified
- Oct 2025
- First submitted
- 2 Jul 2015
- Last updated
- 20 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Arsene A, Oualha M, Rambaud J, Benaboud S, Urien S, Grimaud M, Renolleau S, Leger PL, Hirt D, Treluyer JM, Beranger A. Piperacillin Population Pharmacokinetics in Children Supported With Extracorporeal Membrane Oxygenation. Pediatr Crit Care Med. 2026 Aug 6. doi: 10.1097/PCC.0000000000004016. Online ahead of print.
PubMed 42560139Berthaud 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.
PubMed 41036866Marsaux 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.
PubMed 39630067Collignon 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.
PubMed 36702934de 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.
PubMed 35292609Nguyen 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.
PubMed 33318012Abdalla 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.
PubMed 32988829Beranger 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.
PubMed 29862466Beranger 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.
PubMed 28980166
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Population Pharmacokinetics and Rationalization of Anti-infectives Administration in Critically Ill Children
- ClinicalTrials.gov ID
- NCT02539407
- Acronym / sponsor ID
- OPTIMOME / 2014-01-08
- Keywords
- β-lactam antibiotics, Children, Anti-infectives, Aminoglycosides, glycopeptides, Fluoroquinolone, Fungal, Antiviral
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 3,000 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 11 Sep 2015 (actual)
- Primary completion
- Oct 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 3 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anti-infectives | – | Other: PharmacokineticsAnti-infectives of the following : β-lactam antibiotics, Aminoglycosides, Glycopeptides, Fluoroquinolone, Daptomycin, Rifampin, Trimethoprim, Sulfamethoxazole, Clarithromycin, Fungal, Antiviral Pharmacokinetics |
Who may qualify
- Ages
- 1 day to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Minor patients requiring the administration of anti-infectives
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- Patient and parents having notified to the doctor that they refuse data recovery.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pharmacokinetics | Other | Anti-infectives |
Primary outcome
anti-infectives concentration
Time frame: until 28 days
3 secondary outcomes
number of identified or suspected pathogen
Time frame: until 28 days
composite measure of the health condition
Time frame: until 28 days
predictive variables of underdosing/overdosing of antiinfectives and biological evolution
Time frame: until 28 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2025.
- Derived from this study: PubMed 42560139Arsene A, Oualha M, Rambaud J, Benaboud S, Urien S, Grimaud M, Renolleau S, Leger PL, Hirt D, Treluyer JM, Beranger A. Piperacillin Population Pharmacokinetics in Children Supported With Extracorporeal Membrane Oxygenation. Pediatr Crit Care Med. 2026 Aug 6. doi: 10.1097/PCC.0000000000004016. Online ahead of print.
- Derived from this study: PubMed 41036866Berthaud 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.
- Derived from this study: PubMed 39630067Marsaux 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.
- Derived from this study: PubMed 36702934Collignon 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.
- Derived from this study: PubMed 35292609de 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.
- Derived from this study: PubMed 33318012Nguyen 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.
- Derived from this study: PubMed 32988829Abdalla 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.
- Derived from this study: PubMed 29862466Beranger 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.
- Derived from this study: PubMed 28980166Beranger 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Oualha Mehdi, MD,PhD principal investigator
Hospital Necker - Enfants Malades
Jean-Marc Treluyer, MD, PhD study chair
EA08 Paris Descartes Pharmacologie et Evaluation des thérapeutiques chez l'enfant et la femme enceinte
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pediatric Intensive Care Unit and Pediatric Immuno-hematology Department, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Oualha Mehdi, MD,PhD (+33171196082, mehdi.oualha@nck.aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
anti-infectives concentration (time frame: until 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02539407, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2025; AzTrials last refreshed its copy on 8 Nov 2026.