Prospective Study to Optimize Vancomycin Dosing in Children and Adults Using Computer Software

Prospective Study to Optimize Vancomycin Dosing in Children and Adults Using Multiple-Model Bayesian Adaptive Control

We will compare the percentage of patients having therapeutic vancomycin serum concentrations after current standard dosing, after dosing with our software. We will also include therapeutic outcomes and costs in the analysis.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections
• Intervention / Treatment: Device: BestDose Computer Software

Detailed Description

Recent guidelines to use the antibiotic vancomycin for serious, resistant gram-positive bacterial infections advocate higher plasma concentrations than are routinely achieved with conventional dosing. Moreover, there is wide interpatient variability in vancomycin plasma concentrations, even with standardized dosing. The hypothesis for this study is that dosing vancomycin assisted by computer software and Bayesian algorithms will lead to more rapid and accurate attainment of therapeutic blood vancomycin concentrations in children and adults. This study will enroll 90 patients per year for three years, totaling 270 patients. Eligible patients will be of any age and who are to be prescribed vancomycin by their clinicians for medical indications. Patients with vancomycin-resistant organisms, severe vancomycin allergies or who need dialysis will not be eligible. Participants in the first group of 90 will be treated according to standard care. The second and third groups of patients will be dosed with vancomycin according to the recommendations made by the study team using the BestDose software developed by the USC Laboratory of Applied Pharmacokinetics. The second group will be dosed with the software in its current form, and the third group with funded updates. For all groups, no additional blood samples will be drawn for research purposes; only routinely obtained clinical data will be used. The primary outcome in all groups will be the percentage of participants with appropriate vancomycin concentrations. Secondary outcomes in those who receive vancomycin for at least 72 hours will include effectiveness, toxicity rates, and costs of therapy. Participation in the study will cease at the time of hospital discharge or 72 hours after termination of vancomycin therapy.

• Study Type: Observational
• Enrollment (Actual): 263

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Los Angeles County - University of Southern California Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Hospitalized infants, children, adolescents, and adults who require, but have not started vancomycin therapy for infections with suspected or proven beta-lactam resistant gram-positive bacteria will eligible for enrollment

Description

Inclusion Criteria:

1. Hospitalized infants, children, adolescents, and adults who require, but have not started vancomycin therapy for infections with suspected or proven beta-lactam resistant gram-positive bacteria will eligible for enrollment.
2. Participants will of any age.
3. Participant/parent/legal guardian (as applicable) must be able and willing to provide signed informed consent.

Exclusion Criteria:

1. Prior receipt of vancomycin for the same clinical event (e.g. the same fever of unknown origin in a neutropenic patient defined as <24 hours of no fever)
2. Known colonization or infection with a vancomycin resistant organism (MIC > 2 mg/L)
3. Known hypersensitivity or intolerance to vancomycin
4. Patients on any form of dialysis
5. Not expected to survive >72 hours.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Standard dosing; Vancomycin dosed and monitored according to standard practice
BestDose Computer Software; Vancomycin dosed using BestDose computer software, targeting AUC rather than trough concentrations	Device: BestDose Computer Software; BestDose is made by the USC Laboratory of Applied Pharmacokinetics. It uses a multiple-model, Bayesian adaptive control algorithm to find the maximally precise dose that will achieve a user-specified target concentration or concentrations.
BestDose Computer Software 2; Vancomycin dosed using BestDose computer software, targeting AUC rather than trough concentrations and with computer-generated suggested optimal blood sampling times	Device: BestDose Computer Software; BestDose is made by the USC Laboratory of Applied Pharmacokinetics. It uses a multiple-model, Bayesian adaptive control algorithm to find the maximally precise dose that will achieve a user-specified target concentration or concentrations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to therapeutic vancomycin blood concentration	Within first week of dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of blood samples sent for vancomycin concentration measurement		Duration of therapy, an average of 10 days in the hospital
Incidence of nephrotoxicity	Defined as >0.5 mg/dL or >50% rise from baseline serum creatinine	Duration of therapy, an average of 10 days in the hospital

Collaborators and Investigators

• Sponsor: Children's Hospital Los Angeles
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Michael Neely, MD, Children's Hospital Los Angeles

Publications and helpful links

General Publications

• Neely MN, Kato L, Youn G, Kraler L, Bayard D, van Guilder M, Schumitzky A, Yamada W, Jones B, Minejima E. Prospective Trial on the Use of Trough Concentration versus Area under the Curve To Determine Therapeutic Vancomycin Dosing. Antimicrob Agents Chemother. 2018 Jan 25;62(2):e02042-17. doi: 10.1128/AAC.02042-17. Print 2018 Feb.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2012
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 4, 2016

Study Registration Dates

• First Submitted: August 6, 2013
• First Submitted That Met QC Criteria: August 27, 2013
• First Posted (Estimate): August 30, 2013

Study Record Updates

• Last Update Posted (Actual): February 20, 2018
• Last Update Submitted That Met QC Criteria: February 16, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Vancomycin; Pharmacokinetics; Pharmacodynamics; Decision support
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections
• Other Study ID Numbers: LACUSC-Van-01; R01GM068968 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual data requests will be evaluated on a case-by-case basis.