Precision Dosing of Vancomycin in Critically Ill Children

Study Overview
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Brief Summary
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The overall objective of this project is to investigate the large-scale utility of MIPD of vancomycin at point-of-care in ICU children. This evaluation includes a comparison with the more standard approach on Clinical and patient-oriented measures.

Detailed Description
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Vancomycin is an antibiotic with a narrow therapeutic-toxic margin. This means that the minimum and maximum target blood target levels differ little from each other. Too low concentrations will reduce the effect of the antibiotic; higher concentrations may result in serious side effects, including renal toxicity. Vancomycin dosing tailored to the critically ill child is challenging. Currently, the starting dose of vancomycin is calculated on a milligram per kilogram basis, which is the same for all patients. The dose is then adjusted based on a measured vancomycin blood concentration (if too high or too low). Despite this measurement, quickly achieving target concentrations remains a major challenge. This multicenter, individual randomized study investigates the added value of a user-friendly computer program for calculating the vancomycin dose in critically ill children, compared to the current standard-of-care. Specifically, the investigators will study whether the use of this computer program leads to a shorter time to reach target concentrations, a reduction in the number and severity of side effects on the kidney, a reduction in patient burden, and a reduction in time to cure and duration of hospitalization.

Official Title
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A Multicentric, Randomised Controlled Clinical Trial to Study the Impact of Bedside Model-informed Precision Dosing of Vancomycin in Critically Ill Children

Conditions
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Vancomycin

Intervention / Treatment
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* Device: vancomycin model-informed precision dosing
* Drug: Vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age: 0-18 years admitted to ICU or PHO unit suspected or confirmed Gram positive infection planned to start on intravenous intermittent or continuous infusion vancomycin treatment informed consent signed by parents or legal representatives not previously enrolled in this trial Exclusion Criteria: extracorporeal treatment at inclusion or started during treatment (extracorporeal membrane oxygenation, dialysis, body cooling) n or p RIFLE category failure at inclusion (Day 0) (see section 8.1.2. screening) Known chronic kidney disease as defined by the KDIGO definition as: structural or functional abnormalities of the kidney regardless of GFR for < 3 months or GFR < 60ml/min/1.73m² for ≥ 3 months. eGFR is estimated using the modified Schwartz equation patient death is deemed imminent and inevitable

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care Vancomycin treatment<br>Vancomycin standard-of-care dosing and therapeutic drug monitoring, according to institutional guidelines during 30 day study period | Drug: Vancomycin<br>* Vancomycin treatment<br>|
| Experimental: vancomycin model-informed precision dosing<br>Area Under the Concentration (AUC)-time curve/MIC-based model-informed precision dosing of vancomycin using a CE labelled dosing calculator during 30 day study period | Device: vancomycin model-informed precision dosing<br>* A CE labelled dosing calculator is used for a priori and a posteriori calculation of vancomycin dose using a target AUC between 400-600 mg*h/L<br>* Other names: dosing calculator;Drug: Vancomycin<br>* Vancomycin treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients reaching target 24hAUC/MIC | therapeutic AUC/MIC target range is 400-600 | 24 to 48 hours after start vancomycin treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with (worsening) acute kidney injury during vancomycin treatment | AKI categories are defined according to the neonatal and pediatric RIFLE criteria | from start date of vancomycin treatment until stop date vancomycin treatment or study day 30, whichever comes first | 
| Proportion of patients reaching target 24h AUC/MIC | therapeutic AUC/MIC target range is 400-600 | 48-72 hours after start vancomycin treatment | 
| Time to clinical cure | Time to clinical cure is defined as the time interval (in days) from start to completion of the vancomycin vancomycin treatment, without recommencement of antibiotics for the same indication within 48h after stop. | 30 day study period | 
| Ward unit length-of-stay | Ward unit length-of-stay is calculated from day of ward unit admission to day of ward unit discharge. | 30 day study period | 
| Hospital length-of-stay | Hospital unit length-of-stay is calculated from day of hospital admission to day of hospital discharge. | 30 day study period | 
| 30 day all cause mortality | 30 day all cause mortality is measured 30 days after randomisation. | 30 day study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vancomycin, model-informed precision dosing, critically ill children, dose calculator