Precision Dosing of Vancomycin in Critically Ill Children (BENEFICIAL)

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

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.

Study Overview

• Status: Completed
• Conditions: Vancomycin
• Intervention / Treatment: Drug: Vancomycin; Device: vancomycin model-informed precision dosing

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 314
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Bruges, Belgium
    • AZ Sint-Jan Brugge-Oostende AV
  • Brussels, Belgium
    • Uz Brussel
  • Brussels, Belgium
    • Cliniques Universitaires de Saint Luc
  • Brussels, Belgium
    • Hopital universitaire de Reine Fabiola
  • Ghent, Belgium
    • Ghent University Hospital
  • Leuven, Belgium
    • UZ Leuven
  • Brussels Capital
    • Brussels, Brussels Capital, Belgium
      • Erasme

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care Vancomycin treatment; Vancomycin standard-of-care dosing and therapeutic drug monitoring, according to institutional guidelines during 30 day study period	Drug: Vancomycin; Vancomycin treatment
Experimental: vancomycin model-informed precision dosing; 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	Drug: Vancomycin; Vancomycin treatment; Device: vancomycin model-informed precision dosing; 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; Other Names: dosing calculator

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative number of additional blood samples during treatment in patients with clinical cure	An additional blood sample is defined as a sample for vancomycin TDM taken at another timepoint of routine biochemical monitoring samples.	from start date of vancomycin treatment until stop date vancomycin treatment or study day 30, whichever comes first in patients with clinical cure
Number of additional blood samples to first target attainment during vancomycin treatment	An additional blood sample is defined as a sample for vancomycin TDM taken at another timepoint of routine biochemical monitoring samples.	from start date of vancomycin treatment until date of first vancomycin target attainment or study day 30, whichever comes first
Proportion of patients reaching target 24h AUC/MIC	therapeutic AUC/MIC target range is 400-600	72-96 hours after start vancomycin treatment
Number of dose adjustments to first target attainment	Target in Model-Informed Precision Dosing arm: 24h AUC/MIC : 400-600; in comparator arm: target concentration range according to institutional guidelines	from start date vancomycin treatment until date of first vancomycin target attainment or study day 30, whichever comes first
Number of trough sampling time errors	only measured for intermittent dosing regimens in the comparator arm.	from start date of vancomycin treatment until stop date vancomycin treatment or study day 30, whichever comes first
Cumulative vancomycin dose and AUC	Total cumulative dose and exposure (AUC) during treatment	from start date of vancomycin treatment until stop date vancomycin treatment or study day 30, whichever comes first

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: University Ghent; Belgium Health Care Knowledge Centre
• Investigators: Principal Investigator: Pieter De Cock, Prof, University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2020
• Primary Completion (Actual): December 14, 2023
• Study Completion (Actual): October 30, 2024

Study Registration Dates

• First Submitted: November 28, 2020
• First Submitted That Met QC Criteria: December 7, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: vancomycin; critically ill children; model-informed precision dosing; dose calculator
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Peptides; Amino Acids, Peptides, and Proteins; Carbohydrates; Glycoconjugates; Glycopeptides; Vancomycin
• Other Study ID Numbers: BC-5429

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No