Precision Dosing of Vancomycin in Critically Ill Children (BENEFICIAL)

Ghent University Hospital (UZ)

Status and phase: Completed; Phase 4

Conditions: Vancomycin

Treatments: Device: vancomycin model-informed precision dosing; Drug: Vancomycin

Study type: Interventional

Funder types: Other

Identifiers

NCT04666948

BC-5429

Details and patient eligibility

About

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.

Full 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.

Enrollment: 314 patients

Sex: All

Ages: Under 15 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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314 participants in 2 patient groups

Standard of Care Vancomycin treatment

Active Comparator group

Description:

Vancomycin standard-of-care dosing and therapeutic drug monitoring, according to institutional guidelines during 30 day study period

Treatment:

Drug: Vancomycin

vancomycin model-informed precision dosing

Experimental group

Description:

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

Treatment:

Drug: Vancomycin

Device: vancomycin model-informed precision dosing