Precision Dosing of Vancomycin in Critically Ill Children

Vancomycin Clinical Trial

— BENEFICIAL  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04666948
• Other study ID #: BC-5429
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: December 28, 2020
• Est. completion date: October 30, 2024

Study information

• Verified date: April 2024
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 314
• Est. completion date: October 30, 2024
• Est. primary completion date: December 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Days to 15 Years

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Vancomycin

Intervention

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

Drug:
• Vancomycin
Vancomycin treatment

Locations

Country	Name	City	State
Belgium	AZ Sint-Jan Brugge-Oostende AV	Bruges
Belgium	Erasme	Brussel
Belgium	Cliniques universitaires de Saint Luc	Brussels
Belgium	Hopital universitaire de Reine Fabiola	Brussels
Belgium	UZ Brussel	Brussels
Belgium	Ghent University Hospital	Ghent
Belgium	UZ Leuven	Leuven

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Ghent	Belgium Health Care Knowledge Centre, Ghent University, Belgium

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	Proportion of patients reaching target 24h AUC/MIC	therapeutic AUC/MIC target range is 400-600	72-96 hours after start vancomycin treatment
Other	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
Other	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
Other	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
Primary	Proportion of patients reaching target 24hAUC/MIC	therapeutic AUC/MIC target range is 400-600	24 to 48 hours after start vancomycin treatment
Secondary	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
Secondary	Proportion of patients reaching target 24h AUC/MIC	therapeutic AUC/MIC target range is 400-600	48-72 hours after start vancomycin treatment
Secondary	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
Secondary	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
Secondary	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
Secondary	30 day all cause mortality	30 day all cause mortality is measured 30 days after randomisation.	30 day study period