Clinical trial NCT04666948: Precision Dosing of Vancomycin in Critically Ill Children
Official title: A Multicentric, Randomised Controlled Clinical Trial to Study the Impact of Bedside Model-informed Precision Dosing of Vancomycin in Critically Ill Children
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Vancomycin
Keywords: vancomycin
model-informed precision dosing
critically ill children
dose calculator
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: Belgium Health Care Knowledge Centre
name: University Ghent
First posted: 2020-12-14
Enrollment: 314
Sex: ALL
Minimum age (years): 0
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients reaching target 24hAUC/MIC
timeFrame: 24 to 48 hours after start vancomycin treatment
Secondary outcomes:
measure: Proportion of patients with (worsening) acute kidney injury during vancomycin treatment
timeFrame: from start date of vancomycin treatment until stop date vancomycin treatment or study day 30, whichever comes first
measure: Proportion of patients reaching target 24h AUC/MIC
timeFrame: 48-72 hours after start vancomycin treatment
measure: Time to clinical cure
timeFrame: 30 day study period
measure: Ward unit length-of-stay
timeFrame: 30 day study period
measure: Hospital length-of-stay
timeFrame: 30 day study period
measure: 30 day all cause mortality
timeFrame: 30 day study period
Other outcomes:
measure: Cumulative number of additional blood samples during treatment in patients with clinical cure
timeFrame: from start date of vancomycin treatment until stop date vancomycin treatment or study day 30, whichever comes first in patients with clinical cure
measure: Number of additional blood samples to first target attainment during vancomycin treatment
timeFrame: from start date of vancomycin treatment until date of first vancomycin target attainment or study day 30, whichever comes first
measure: Proportion of patients reaching target 24h AUC/MIC
timeFrame: 72-96 hours after start vancomycin treatment
measure: Number of dose adjustments to first target attainment
timeFrame: from start date vancomycin treatment until date of first vancomycin target attainment or study day 30, whichever comes first
measure: Number of trough sampling time errors
timeFrame: from start date of vancomycin treatment until stop date vancomycin treatment or study day 30, whichever comes first
measure: Cumulative vancomycin dose and AUC
timeFrame: from start date of vancomycin treatment until stop date vancomycin treatment or study day 30, whichever comes first
Locations:
city: Bruges
country: Belgium
facility: AZ Sint-Jan Brugge-Oostende AV
city: Brussels
country: Belgium
facility: Cliniques universitaires de Saint Luc
city: Brussels
country: Belgium
facility: Hopital universitaire de Reine Fabiola
city: Brussels
country: Belgium
facility: UZ Brussel
city: Brussel
country: Belgium
facility: Erasme
city: Ghent
country: Belgium
facility: Ghent University Hospital
city: Leuven
country: Belgium
facility: UZ Leuven
Study officials:
affiliation: University Hospital, Ghent
name: Pieter De Cock, Prof
role: PRINCIPAL_INVESTIGATOR
References: