Optimizing Vancomycin Therapy in Children

Study Overview
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Brief Summary
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The purpose of Opt Vanc is to evaluate the feasibility of Bayesian dose adaptation, based on a previously-developed population pharmacokinetic (PK) model and a single optimally timed PK sample, to predict vancomycin area under the curve (AUC) in critically ill children.

Detailed Description
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Opt Vanc is an observational study of critically ill children prescribed IV vancomycin for a suspected infection at the Children's Hospital of Philadelphia. This study will evaluate how well Bayesian dose adaptation, based on a previously-developed population pharmacokinetic (PK) model for vancomycin and a single optimally timed vancomycin concentration, can predict vancomycin area under the curve (AUC) in critically ill children. Eligible subjects will be prescribed vancomycin and undergo routine therapeutic drug monitoring (TDM) per standard of care. At the time of TDM, each subject will have a vancomycin concentration obtained at the most informative sampling time to estimate AUC, as determined by the multiple-model optimal sampling function in PMetrics (population PK modeling program). Investigators will then compare the AUC determined using Bayesian estimation and the subject's optimally timed vancomycin concentration to the AUC determined using Bayesian estimation with all available concentrations (TDM samples plus the optimally timed sample). Investigators will also examine how AUC estimation compares to AUC calculated using standard-of-care methods (ie, log-linear equations). Further, Investigators will evaluate how well the population PK model, along with a subject's measured covariates and the optimally timed PK sample, can predict a subject's future vancomycin AUC.

Official Title
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Optimizing Vancomycin Therapy in Children

Conditions
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Sepsis, Critical Illness, Infections, Drug Toxicity

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Administered intravenous vancomycin via intermittent infusion, Eligible for vancomycin AUC monitoring, per the subject's clinical team, and Parental/guardian permission (informed consent). Exclusion Criteria: Receipt of renal replacement therapy, plasmapheresis, or extracorporeal membrane oxygenation (ECMO), or Unable to provide urine and blood samples.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour vancomycin AUC from optimally timed concentration | This 24-hour vancomycin AUC will be estimated using Bayesian estimation based on the population PK model, a subject's measured covariates and the optimally timed vancomycin concentration | within 24-48 hours following enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour vancomycin AUC estimated using all available vancomycin concentrations | This 24-hour vancomycin AUC will be estimated using Bayesian estimation based on the population PK model, a subject's measured covariates and all available measured vancomycin concentrations | within 24-48 hours following enrollment | 
| 24-hour vancomycin AUC calculated using standard-of-care methods | This 24-hour vancomycin AUC will be calculated using standard clinical methods (Zaske-Sawchuk method) | within 24-48 hours following enrollment | 
| Visit 2 vancomycin AUC using optimally timed concentration | The predicted 24-hour vancomycin AUC at visit 2 will be estimated using Bayesian estimation based on the population PK model, a subject's measured covariates and the optimally timed vancomycin concentration at visit 1 | 24-72 hours after visit 1 | 
| Visit 2 vancomycin AUC using all available vancomycin concentrations | The predicted 24-hour vancomycin AUC at visit 2 will be estimated using Bayesian estimation based on the population PK model, a subject's measured covariates and all available vancomycin concentrations | 24-72 hours after visit 1 | 
| Visit 2 vancomycin AUC calculated using standard-of-care methods | This 24-hour vancomycin AUC will be calculated using standard clinical methods (Zaske-Sawchuk method) based on measured concentrations at visit 2 | 24-72 hours after visit 1 | 
| Vancomycin concentrations at Visits 1 and 2 | Vancomycin concentrations will be measured by the Hospital Laboratory | Days 1 to 5 of study participation |