Clinical trial NCT03881800: Ceftazidime in Burn Children
Official title: Population Pharmacokinetics and Dosing Regimens Optimization of Ceftazidime in Critically Ill Burn Children
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Burned Children
Ceftazidime Treatment
Keywords: Ceftazidime
Burned Children
Intensive care
Pharmacokinetic
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2019-03-20
Enrollment: 3
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Burned children requiring the administration of Ceftazidime for the treatment of a documented or suspected bacterial infection

Brief summary: Concentrations and effects of Ceftazidime in critically ill burn 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 burn children.

Optimization of Ceftazidime dosing is therefore desirable for all. The investigators aim to investigate, using a population approach, the pharmacokinetics (PK) of Ceftazidime including PK/pharmacodynamic (PD) targets (fT(%) \> minimal inhibitory concentration (MIC)) and PD endpoints (clinical outcomes) in critically ill burn children. The effects of covariates on Ceftazidime 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. Six blood samples were taken from each patient during dosing interval. The primary PK/ PD targets were Ceftazidime 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 Ceftazidime 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 with burns and in critical illness. Ceftazidime is one of the most anti-infective agents used in this vulnerable population. Given to the expected high BSV, concentrations and effects of Ceftazidime are unpredictable and the risk of under exposure- is thus considerable. Rationalization of Ceftazidime 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 Ceftazidime including usual PK/PD targets (fT(%) \> minimal inhibitory concentration (MIC)) and PD endpoints (clinical outcomes) in critically ill burn children. The effects of developmental and other factors related to critical illness and burns on Ceftazidime 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 a paediatric intensive care unit of Public Hospitals in Paris, France

Intervention:

Patient selection will take place in paediatric intensive care unit. The senior physician proposes the study to holders of parental authority whose child receives or will receive Ceftazidime 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

Eligibility criteria: Inclusion Criteria:

* Patient age: \> 1 month and \< 18 years
* Patient weight \> 3 Kg
* Patient requiring the administration of Ceftazidime for the treatment of a documented or suspected bacterial infection

Exclusion Criteria:

* Patient and parents having notified to the doctor that they refuse data recovery and additional blood sample volume

Primary outcomes:
measure: Ceftazidime concentration
timeFrame: Up to 28 days
Secondary outcomes:
measure: Weight (kg)
timeFrame: Up to 28 days
measure: Body temperature (°C)
timeFrame: Up to 28 days
measure: Creatinine clearance
timeFrame: Up to 28 days
measure: Albumin levels
timeFrame: Up to 28 days
measure: PELOD-2 score (severity score)
timeFrame: Up to 28 days
measure: Percentage of body surface burned
timeFrame: Up to 28 days
measure: C Reactive Protein
timeFrame: Up to 28 days
measure: Relapse
timeFrame: Day 28 after end of Ceftazidime administration
measure: Minimum Inhibitory Concentration (MIC) of the suspected or documented pathogen
timeFrame: Day 28 after end of Ceftazidime administration
Other outcomes:
Locations:
city: Paris
country: France
facility: Hospital Necker - Enfants Malades (Public Hospitals of Paris)
Study officials:
affiliation: Hospital Necker - Enfants Malades
name: Mehdi OUALHA, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: