Optimizing Vancomycin Therapy in Children

Completed

Conditions: Sepsis
Infections
Critical Illness
Drug Toxicity

Registration Number: NCT05691309

Lead Sponsor: Children's Hospital of Philadelphia

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 29

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.

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
24-hour Vancomycin Area Under the Curve (AUC) From Optimally Timed Concentration	within 24-48 hours following enrollment	This 24-hour vancomycin area under the curve (AUC) will be estimated using Bayesian estimation based on the population pharmacokinetic (PK) model, a subject's measured covariates and the optimally timed vancomycin concentration

Secondary Outcome Measures

Name	Time	Method
24-hour Vancomycin Area Under the Curve (AUC) Estimated Using All Available Vancomycin Concentrations	within 24-48 hours following enrollment	This 24-hour vancomycin area under the curve (AUC) will be estimated using Bayesian estimation based on the population pharmacokinetic (PK) model, a subject's measured covariates and all available measured vancomycin concentrations
24-hour Vancomycin Area Under the Curve (AUC) Calculated Using Standard-of-care Methods	within 24-48 hours following enrollment	This 24-hour vancomycin area under the curve (AUC) will be calculated using standard clinical methods (Zaske-Sawchuk method)
Visit 2 Vancomycin Area Under the Curve (AUC) Using Optimally Timed Concentration	24-72 hours after visit 1	The predicted 24-hour vancomycin area under the curve (AUC) at visit 2 will be estimated using Bayesian estimation based on the population pharmacokinetic (PK) model, a subject's measured covariates and the optimally timed vancomycin concentration at visit 1
Visit 2 Vancomycin Area Under the Curve (AUC) Using All Available Vancomycin Concentrations	24-72 hours after visit 1	The predicted 24-hour vancomycin area under the curve (AUC) at visit 2 will be estimated using Bayesian estimation based on the population pharmacokinetic (PK) model, a subject's measured covariates and all available vancomycin concentrations
Visit 2 Vancomycin Area Under the Curve (AUC) Calculated Using Standard-of-care Methods	24-72 hours after visit 1	This 24-hour vancomycin area under the curve (AUC) will be calculated using standard clinical methods (Zaske-Sawchuk method) based on measured concentrations at visit 2