Model-informed Precision Dosing of Vancomycin in Adults

Study Overview
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Brief Summary
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The overall objective of this project is to investigate the utility of model-informed precision dosing (MIPD) of vancomycin in non-critically ill adults. This evaluation includes a comparison with the more standard approach on clinical and patient-oriented measures.

Detailed Description
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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 individual patient is challenging. Currently, the vancomycin dose is 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 non-critically ill adults, 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 and a reduction in patient burden.

Official Title
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Impact of Model-informed Precision Dosing of Vancomycin in Adults: a Randomized, Clinical Trial

Conditions
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Vancomycin

Intervention / Treatment
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* Device: Vancomycin model-informed precision dosing
* Drug: Vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older admitted to a participating ward unit a suspected or confirmed Gram positive infection planned to start of started on intravenous continuous infusion vancomycin treatment participant or legal representative signed the informed consent form not previously enrolled in this trial Exclusion Criteria: serum creatinine level at inclusion is above 2.5 mg/dL undergoing extracorporeal treatment at inclusion (e.g. extracorporeal membrane oxygenation, dialysis, body cooling) patient death is deemed imminent and inevitable.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care Vancomycin treatment<br>Vancomycin standard-of-care dosing and therapeutic drug monitoring (TDM), according to institutional guidelines during 20 day study period | Drug: Vancomycin<br>* Vancomycin treatment<br>* Other names: Vancomycin treatment;|
| Experimental: Vancomycin model-informed precision dosing<br>Area Under the Concentration-time curve ((AUC)/Minimal Inhibitory Concentration (MIC)-based model-informed precision dosing of vancomycin using a dosing calculator during 20 day study period | Device: Vancomycin model-informed precision dosing<br>* A dosing calculator is used for a posteriori calculation of vancomycin dose using a target AUC/MIC between 400-600 mg*h/L<br>* Other names: Dosing calculator;Drug: Vancomycin<br>* Vancomycin treatment<br>* Other names: Vancomycin treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients reaching target 24h AUC/MIC | Therapeutic AUC/MIC target range is 400-600 | 48 to 72 hours after start vancomycin treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with (worsening) acute kidney injury (AKI) during vancomycin treatment | AKI categories are defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria from stage 1 to 3 (worst) | From start date of vancomycin treatment until stop date vancomycin treatment or study day 20, whichever comes first | 
| Proportion of patients reaching target 24h AUC/MIC | Therapeutic AUC/MIC target range is 400-600 | 72 to 96 hours after start vancomycin treatment | 
| Proportion of time within therapeutic target | Therapeutic AUC/MIC target range is 400-600 | From start date of vancomycin treatment until stop date vancomycin treatment or study day 20, whichever comes first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vancomycin, model-informed precision dosing, dose calculator, non-critically ill adults