Improving Dosing of Vancomycin in Young Infants With Infections (VANCAPP)

The VANcomycin Cohort Study - Assessing Precise Dosing and Prompt Drug Monitoring to Improve Attainment of Target Concentrations (Part 1)

Current dosing regimens for vancomycin result in many young infants not reaching the target level of vancomycin in the blood at steady state (when the blood is in equilibrium at 24-48 hours).The purpose of this study is to assess an improved method of calculating the dose of vancomycin ('model-based dosing') in young infants with infections in order for them to achieve the target vancomycin level at steady state. A dosing calculator (which will be available through a web application) will be used for the dose calculation.

Study Overview

• Status: Completed
• Conditions: Sepsis; Bacteremia; Infection
• Intervention / Treatment: Drug: Vancomycin - model-based dosing regimen

Detailed Description

Standard of care dosing of vancomycin in young infants is based on weight (eg. 15 mg/kg/dose). There is evidence that many young infants who are prescribed vancomycin using this calculation will not have enough vancomycin in the blood at steady state to treat an infection effectively. In this study a dosing calculator will be used to generate each participant's dose with the aim to improve the number of participant's who achieve the target vancomycin level (10 - 20 mg/L) at steady state. The dosing calculator is based on a pharmacokinetic/pharmacodynamic model of vancomycin which was built from prospective data. The participant's weight, post-menstrual age, creatinine and target vancomycin level will be entered into the dosing calculator (available on a web application), and the calculator will provide the dosing regimen for that participant. The participant will have the vancomycin level checked at 24-48 hours to assess if the target level has been achieved.

This study is 'part 1' of the study protocol (version 4.0) as approved under HREC reference number HREC/51942/RCHM-2019. This protocol also includes a second study, 'part 2', which will be registered with clinicaltrials.gov separately. Part 2 will assess the use of early drug monitoring and early dose adjustment to achieve the target vancomycin level in the blood at steady state. Part 1 of this protocol will be completed before part 2 begins recruitment. Part 1 and part 2 are two separate studies and the results of each part will not be compared to one another. However, each part will be compared to a retrospective control arm - infants from the VANC randomized controlled trial (NCT02210169) who received standard intermittent infusion of vancomycin dosing (as per British National Formulary for children. 15mg/kg/dose) and standard therapeutic drug monitoring.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2031
      • Royal Hospital for Women
    • Sydney, New South Wales, Australia
      • Children's Hospital at Westmead
  • Victoria
    • Melbourne, Victoria, Australia, 3052
      • Royal Children's Hospital Melbourne
    • Melbourne, Victoria, Australia
      • Monash Children's Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Infants aged 0 - 90 days old
• Suspected infection requiring treatment with vancomycin for 48 hours or more (as determined by the clinical team)
• Post-Menstrual age (PMA) matched to PMA-group from retrospective control group

Exclusion Criteria:

• Infants with corrected gestational age of less than 25 weeks
• Infants weighing less than 500g
• Known allergy to any glycopeptide antibiotic
• Vancomycin administered within the previous 72 hours
• Infants receiving any form of extracorporeal life support
• Renal impairment
• Previously enrolled in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Model-based vancomycin dosing; Participants will receive model-based intermittent intravenous vancomycin dosing as calculated by the dosing calculator available on a web application. Participants will then have routine therapeutic drug monitoring and linear dose adjustments.

Drug: Vancomycin - model-based dosing regimen; A dosing calculator based on a population pharmacokinetic model for vancomycin will be used to generate a participant's intermittent vancomycin dosing regimen. The participant's post-menstrual age, weight, creatinine and the target trough vancomycin level will be entered into the dosing calculator and the dose will be generated (intermittent infusion, dosing frequency will be from 1 to 4 times per day according to the corrected gestational age).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of young infants achieving target trough vancomycin concentrations (10 to 20 mg/L) at the first steady-state level when using a model-based dosing regimen	From first vancomycin dose (immediately after consent) to steady state level taken at 24-48 hours post-first-dose.

Secondary Outcome Measures

Outcome Measure	Time Frame
The proportion of young infants with supra- (defined as >20mg/L) or sub- (defined as <10mg/L) therapeutic vancomycin concentrations at the first steady state level using a model-based dosing regimen (through a web application)	From first vancomycin dose (immediately after consent) to steady state level taken at 24-48 hours post-first-dose.
The proportion of young infants who are excluded from the study due to the model-based dosing regimen providing a total daily dose which exceeds 80 mg/kg/day despite a target trough concentration of 10 mg/L.	From consent to calculation of vancomycin dose (immediately after consent)
The frequency of drug-related adverse events (including infusion-related adverse events and nephrotoxicity).	From first vancomycin dose (immediately after consent) to completion of vancomycin therapy (as determined by clinical team, an average of 5 days)
The frequency of drug administration errors	From first vancomycin dose to completion of vancomycin therapy (as determined by clinical team, an average of 5 days)

Collaborators and Investigators

• Sponsor: Murdoch Childrens Research Institute
• Collaborators: University of Otago; Sydney Children's Hospitals Network; Royal Children's Hospital; Monash Health; Royal Hospital For Women
• Investigators: Principal Investigator: Amanda Wilkins, MBBS, Murdoch Children'S Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2019
• Primary Completion (Actual): December 29, 2020
• Study Completion (Actual): January 3, 2021

Study Registration Dates

• First Submitted: July 31, 2019
• First Submitted That Met QC Criteria: August 2, 2019
• First Posted (Actual): August 5, 2019

Study Record Updates

• Last Update Posted (Actual): August 26, 2021
• Last Update Submitted That Met QC Criteria: August 24, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Infections; Bacteremia; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: HREC2019.059

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