Clinical Decision Support Tool for Vancomycin Dosing in Children

NCT04911270 | Completed DMC

• 2 other identifiers: HP-00093185T32HD087969
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the pharmacokinetic and pharmacodynamic dosing properties of intravenous vancomycin in pediatric patients using a novel computer decision support (CDS) tool called Lyv. Dosing will be individualized based on AUC24/MIC. The results will be compared to matched historical controls.

Conditions

Gram-Positive Bacterial Infections; Vancomycin; Pharmacokinetics; Pharmacodynamics

Keywords

computer decision support; gram positive bacterial infections; sepsis; vancomycin

Outcome Measures

Primary Outcomes (1)

• AUC24/MIC target attainment of vancomycin after first dose using the clinical decision support tool compared to dosing using the current hospital method

  Vancomycin level will be drawn after first dose of antibiotic. The level will be entered into the CDS tool and AUC24/MIC target attainment will be generated. If the level is not in range, the CDS tool will generate a new dose for future doses.

  2-6 hours post first dose

Secondary Outcomes (3)

• To characterize vancomycin pharmacokinetics and evaluate the factors that affect variability in achievement of an AUC24/MIC > 400 in pediatric patients

  From start to end of antibiotic therapy, or a max of 7 days

• To evaluate the incidence of nephrotoxicity for dosing vancomycin using the decision support tool compared to dosing using the current hospital method

  From start to end of antibiotic therapy, or a max of 7 days

• To evaluate the accuracy of the clinical decision support system in predicting the AUC24/MIC

  From start to end of antibiotic therapy, or a max of 7 days

Other Outcomes (1)

• The number of dose changes before getting to the therapeutic dose, defined as the dose achieving AUC24/MIC > 400

  From start to end of antibiotic therapy, or a max of 7 days

Study Arms (2)

Intervention Group- Computer Decision Support Tool

EXPERIMENTAL

Patients enrolled in the study will be started on IV vancomycin which will be dosed based on the LYV CDS tool, which will dose patients based on AUC24/MIC. Dosing will be adjusted based on vancomycin levels that will be drawn throughout the hospital stay. All patients prospectively enrolled into this study will be in the intervention group. Results will be compared to the retrospectively matched historical controls.

Device: Computer Decision Support Tool Intervention Group

Matched Historical Controls

OTHER

Match historical controls are patients that were on IV vancomycin with dose adjustments based on vancomycin trough levels. Patients in this study arm will be retrospective patients that will be matched with the intervention group.

Other: Matched Historical Controls

Interventions

Computer Decision Support Tool Intervention Group DEVICE

Computer Decision Support Tool using Bayesian estimation to dose IV vancomycin in pediatric patients using AUC24/MIC

Also known as: Lyv

Intervention Group- Computer Decision Support Tool

Matched Historical Controls OTHER

Vancomycin dosing based on standard hospital methods, with dose adjustments based on vancomycin trough targets

Also known as: standard of care

Matched Historical Controls

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Hospitalized infants and children from postmenstrual age of 38 weeks to age 19 years Requiring IV vancomycin, regardless of indication
• Parent or legally authorized representative is willing to provide permission and sign the informed consent document; subjects assent, when appropriate
• Hospitalized neonates, infants, children, adolescents who require, but have not been initiated on intravenous vancomycin therapy

You may not qualify if:

• Patients who had received vancomycin during previous 2 weeks
• Patients with end-stage renal disease, receiving hemodialysis or receiving continuous renal replacement therapy
• On oral or intraperitoneal vancomycin
• Receiving extracorporeal therapy, including extracorporeal membrane oxygenation, continuous renal replacement therapy, and extracorporeal liver support
• Will only receive a single dose of vancomycin
• Known to be pregnant
• Is brain dead or has suspected brain death

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Center for Translational Medicine at the School of Pharmacy: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Related Publications (10)

• Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis. 2011 Feb 1;52(3):285-92. doi: 10.1093/cid/cir034.

  PMID: 21217178 BACKGROUND

• Iwamoto M, Mu Y, Lynfield R, Bulens SN, Nadle J, Aragon D, Petit S, Ray SM, Harrison LH, Dumyati G, Townes JM, Schaffner W, Gorwitz RJ, Lessa FC. Trends in invasive methicillin-resistant Staphylococcus aureus infections. Pediatrics. 2013 Oct;132(4):e817-24. doi: 10.1542/peds.2013-1112. Epub 2013 Sep 23.

  PMID: 24062373 BACKGROUND

• Gerber JS, Coffin SE, Smathers SA, Zaoutis TE. Trends in the incidence of methicillin-resistant Staphylococcus aureus infection in children's hospitals in the United States. Clin Infect Dis. 2009 Jul 1;49(1):65-71. doi: 10.1086/599348.

  PMID: 19463065 BACKGROUND

• Moise-Broder PA, Forrest A, Birmingham MC, Schentag JJ. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet. 2004;43(13):925-42. doi: 10.2165/00003088-200443130-00005.

  PMID: 15509186 BACKGROUND

• Giachetto GA, Telechea HM, Speranza N, Oyarzun M, Nanni L, Menchaca A. Vancomycin pharmacokinetic-pharmacodynamic parameters to optimize dosage administration in critically ill children. Pediatr Crit Care Med. 2011 Nov;12(6):e250-4. doi: 10.1097/PCC.0b013e3181fe4047.

  PMID: 21057350 BACKGROUND

• Gous AG, Dance MD, Lipman J, Luyt DK, Mathivha R, Scribante J. Changes in vancomycin pharmacokinetics in critically ill infants. Anaesth Intensive Care. 1995 Dec;23(6):678-82. doi: 10.1177/0310057X9502300603.

  PMID: 8669599 BACKGROUND

• Le J, Bradley JS, Murray W, Romanowski GL, Tran TT, Nguyen N, Cho S, Natale S, Bui I, Tran TM, Capparelli EV. Improved vancomycin dosing in children using area under the curve exposure. Pediatr Infect Dis J. 2013 Apr;32(4):e155-63. doi: 10.1097/INF.0b013e318286378e.

  PMID: 23340565 BACKGROUND

• Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL; AWARE Investigators. Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults. N Engl J Med. 2017 Jan 5;376(1):11-20. doi: 10.1056/NEJMoa1611391. Epub 2016 Nov 18.

  PMID: 27959707 BACKGROUND

• Heil EL, Claeys KC, Mynatt RP, Hopkins TL, Brade K, Watt I, Rybak MJ, Pogue JM. Making the change to area under the curve-based vancomycin dosing. Am J Health Syst Pharm. 2018 Dec 15;75(24):1986-1995. doi: 10.2146/ajhp180034. Epub 2018 Oct 17. No abstract available.

  PMID: 30333114 BACKGROUND

• Hughes DM, Goswami S, Keizer RJ, Hughes MA, Faldasz JD. Bayesian clinical decision support-guided versus clinician-guided vancomycin dosing in attainment of targeted pharmacokinetic parameters in a paediatric population. J Antimicrob Chemother. 2020 Feb 1;75(2):434-437. doi: 10.1093/jac/dkz444.

  PMID: 31670812 BACKGROUND

MeSH Terms

Conditions

Gram-Positive Bacterial Infections; Sepsis

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: The intervention group includes pediatric patients that will be started on intravenous (IV) vancomycin. Once consent is obtained, their age, weight, length, sex, serum creatinine will be entered into Lyv which will generate a dose for the patient. Levels will be drawn intermittently and dosage will be adjusted accordingly. This interventional group will be compared to matched historical controls who were treated with IV vancomycin with dosage adjustments based on trough levels.

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: June 3, 2021
• Study Start: May 9, 2022
• Primary Completion: April 12, 2024
• Study Completion: May 10, 2025
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)