Optimizing Vancomycin Therapy in Children (Opt Vanc)

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.

Study Overview

• Status: Completed
• Conditions: Infections; Sepsis; Critical Illness; Drug Toxicity

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.

• Study Type: Observational
• Enrollment (Actual): 29

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants aged 1-17 years receiving standard of care IV vancomycin for a suspected or confirmed infection will be enrolled at Children's Hospital of Philadelphia.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Study Cohort; Recipients of vancomycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour Vancomycin Area Under the Curve (AUC) From Optimally Timed Concentration	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	within 24-48 hours following enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour Vancomycin Area Under the Curve (AUC) Estimated Using All Available Vancomycin Concentrations	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	within 24-48 hours following enrollment
24-hour Vancomycin Area Under the Curve (AUC) Calculated Using Standard-of-care Methods	This 24-hour vancomycin area under the curve (AUC) will be calculated using standard clinical methods (Zaske-Sawchuk method)	within 24-48 hours following enrollment
Visit 2 Vancomycin Area Under the Curve (AUC) Using Optimally Timed Concentration	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	24-72 hours after visit 1
Visit 2 Vancomycin Area Under the Curve (AUC) Using All Available Vancomycin Concentrations	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	24-72 hours after visit 1
Visit 2 Vancomycin Area Under the Curve (AUC) Calculated Using Standard-of-care Methods	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	24-72 hours after visit 1

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2022
• Primary Completion (Actual): November 22, 2023
• Study Completion (Actual): November 22, 2023

Study Registration Dates

• First Submitted: December 29, 2022
• First Submitted That Met QC Criteria: January 17, 2023
• First Posted (Actual): January 20, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Chemically-Induced Disorders; Critical Illness; Drug-Related Side Effects and Adverse Reactions
• Other Study ID Numbers: 22-020240; 5K23HD091365 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No