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 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, it is investigated 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.
| Summary of results |
|---|
| This randomised study followed 332 patients. The percentage of patients achieving target concentrations was significantly lower in the standard care group, compared with the group where the dose of vancomycin was calculated using the computer programme (intervention group). The percentage of patients with renal side effects and death rate were lower in the intervention group, but this difference was not statistically significant. There was also no difference in time to cure and duration of hospitalisation. Nonetheless, the study did manage to prove that the required dose and exposure were significantly lower in the intervention group. A qualitative study assessing experiences and perspectives on the implementation of these computer programmes in routine care is ongoing in a selection of participating centres. |
| Title |
A Multicentric, Randomised Controlled Clinical Trial To Study The Impact Of Bedside Model-Informed Precision Dosing Of Vancomycin In Critically Ill Children |
|
Participants (P) |
Critically ill children started on intravenous vancomycin treatment. |
|
Intervention (I) |
Area Under the Concentration (AUC)-time curve/MIC-based model-informed precision dosing of vancomycin using a CE labelled dosing calculator. |
|
Control (C) |
Vancomycin standard-of-care dosing and therapeutic drug monitoring, according to institutional guidelines. |
|
Outcome (O) |
Proportion of patients reaching target 24hAUC/MIC between 24 and 48h after start vancomycin treatment. |
|
Trial Design |
Prospective, multicentric, individual randomised controlled trial. |
|
Sample Size |
390 patients |
|
Trial duration |
28 months |
|
Budget |
€1.26M |
|
Sponsor |
UZ Gent |
|
Chief Investigator |
Dr. Pieter De Cock |
|
Number of participating sites |
8 hospitals 14 wards |
|
External partner |
Insight RX |
| Protocol | Download protocol |
| Results | view publication Lancet Child and Adolescent Health |
For timelines and recruitment, see dashboard
Clinicaltrials.gov: NCT04666948
Webpage: www.uzgent.be/beneficial
2018 Investigator led
