Precision Dosing of Vancomycin in Critically Ill Children

Phase 4

Active, not recruiting

• Conditions: Vancomycin
• Interventions: Device: vancomycin model-informed precision dosing; Drug: Vancomycin

• Registration Number: NCT04666948
• Lead Sponsor: University Hospital, Ghent

Brief Summary

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

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 Timeline

• Study First Submitted: 2020-11-28
• Study First Submitted QC: 2020-12-07
• Study First Posted: 2020-12-14
• Study Start: 2020-12-28
• Primary Completion: 2023-12-14
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-11
• Last Update Posted: 2024-04-12
• Study Completion: 2024-10-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 314

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
vancomycin model-informed precision dosing	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
Standard of Care Vancomycin treatment	Vancomycin	Vancomycin standard-of-care dosing and therapeutic drug monitoring, according to institutional guidelines during 30 day study period
vancomycin model-informed precision dosing	Vancomycin	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

Primary Outcome Measures

Name	Time	Method
Proportion of patients reaching target 24hAUC/MIC	24 to 48 hours after start vancomycin treatment	therapeutic AUC/MIC target range is 400-600

Secondary Outcome Measures

Name	Time	Method
Proportion of patients reaching target 24h AUC/MIC	48-72 hours after start vancomycin treatment	therapeutic AUC/MIC target range is 400-600
Proportion of patients with (worsening) acute kidney injury during vancomycin treatment	from start date of vancomycin treatment until stop date vancomycin treatment or study day 30, whichever comes first	AKI categories are defined according to the neonatal and pediatric RIFLE criteria
Time to clinical cure	30 day study period	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.
Ward unit length-of-stay	30 day study period	Ward unit length-of-stay is calculated from day of ward unit admission to day of ward unit discharge.
Hospital length-of-stay	30 day study period	Hospital unit length-of-stay is calculated from day of hospital admission to day of hospital discharge.
30 day all cause mortality	30 day study period	30 day all cause mortality is measured 30 days after randomisation.

Trial Locations

Locations (7)

AZ Sint-Jan Brugge-Oostende AV; 🇧🇪 Bruges, Belgium

Cliniques universitaires de Saint Luc; 🇧🇪 Brussels, Belgium

Ghent University Hospital; 🇧🇪 Ghent, Belgium

UZ Brussel; 🇧🇪 Brussels, Belgium

Erasme; 🇧🇪 Brussel, Belgium

Hopital universitaire de Reine Fabiola; 🇧🇪 Brussels, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium