Clinical trial NCT01932034: Prospective Study to Optimize Vancomycin Dosing in Children and Adults Using Computer Software
Official title: Prospective Study to Optimize Vancomycin Dosing in Children and Adults Using Multiple-Model Bayesian Adaptive Control
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Bacterial Infections
Keywords: Vancomycin
Pharmacokinetics
Pharmacodynamics
Decision support
Lead sponsor: Children's Hospital Los Angeles
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
First posted: 2013-08-30
Enrollment: 263
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to therapeutic vancomycin blood concentration
timeFrame: Within first week of dosing
Secondary outcomes:
measure: Number of blood samples sent for vancomycin concentration measurement
timeFrame: Duration of therapy, an average of 10 days in the hospital
measure: Incidence of nephrotoxicity
timeFrame: Duration of therapy, an average of 10 days in the hospital
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Los Angeles County - University of Southern California Medical Center
state: California
Study officials:
affiliation: Children's Hospital Los Angeles
name: Michael Neely, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.