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Improving Therapeutic Drug Monitoring and Dosing for Vancomycin in Young Infants With Infections (VANCAPP) (Part 2) (VANCAPP)

Primary Purpose

Sepsis, Infections, Bacteremia

Status
Not yet recruiting
Phase
Phase 4
Locations
Australia
Study Type
Interventional
Intervention
First-dose trough dose adjustment calculator - using early TDM (first-dose trough) to determine an early dose adjustment if the predicted steady-state trough is outside of target range (10-20mg/L)
Sponsored by
Murdoch Childrens Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sepsis

Eligibility Criteria

0 Days - 90 Days (Child)All SexesDoes not accept healthy volunteers

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) Exclusion Criteria: Infants with a 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

Sites / Locations

  • Royal Children's Hospital Melbourne
  • Monash Newborn
  • Royal Hospital for Women
  • The Children's Hospital at Westmead

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vancomycin first-dose trough dose adjustment calculation

Arm Description

Participants will have individualised model-based intermittent vancomycin dosing using the Vanc App dosing calculator (as used in VANC APP Part 1, see clinicaltrials.gov ID: NCT04044703). A first-dose trough concentration will be measured for each participant and the clinician will then enter that concentration into the web application ('First-dose trough dose adjustment calculator'). A dose adjustment will be generated by the calculator if the predicted steady-state level is outside of target range. If the predicted steady-state level is within target range (10-20mg/L) the calculator will recommend continuing with the same dose. The vancomycin concentration is then measured at steady state to determine if the target concentration has been achieved.

Outcomes

Primary Outcome Measures

Target concentration at first steady-state concentration
The proportion of young infants achieving target trough serum vancomycin concentrations (10 to 20 mg/L) at first steady-state level when model-based dosing is used followed by early therapeutic drug monitoring (and dose adjustment) after the first dose

Secondary Outcome Measures

Sub- and supratherapeutic concentrations at first steady-state concentration
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 when model-based dosing is used followed by early therapeutic drug monitoring (and dose adjustment) after the first dose
Drug-related adverse effects
The frequency of drug-related adverse effects (infusion-related and nephrotoxicity).

Full Information

First Posted
March 5, 2023
Last Updated
August 7, 2023
Sponsor
Murdoch Childrens Research Institute
Collaborators
Royal Children's Hospital, Royal Hospital For Women, Sydney Children's Hospitals Network, Monash Health
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1. Study Identification

Unique Protocol Identification Number
NCT05770622
Brief Title
Improving Therapeutic Drug Monitoring and Dosing for Vancomycin in Young Infants With Infections (VANCAPP) (Part 2)
Acronym
VANCAPP
Official Title
The VANcomycin Cohort Study - Assessing Precise Dosing and Prompt Drug Monitoring to Improve Attainment of Target Concentrations (Part 2)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Murdoch Childrens Research Institute
Collaborators
Royal Children's Hospital, Royal Hospital For Women, Sydney Children's Hospitals Network, Monash Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A challenge to intermittent vancomycin dosing in young infants is the avoidable delay caused by the need to wait until steady state (i.e. when the drug concentrations are in equilibrium) to measure a vancomycin concentration, as this generally occurs 24 to 48 hours after starting treatment. If the target concentration is not achieved, the dose needs to be adjusted, resulting in further delays in an infant achieving the concentration required to treat their infection. The purpose of this study is to assess the use of early therapeutic drug monitoring (first-dose trough) and, if needed, early dose adjustment, in achieving target vancomycin concentrations at steady state. A dose adjustment calculator (available through a web application) will be used to determine the need for dose adjustment (based on predicted steady state concentration) and recommend an adjusted dose if required.
Detailed Description
Therapeutic drug monitoring (TDM) for vancomycin is done once the drug is in steady state. In young infants, this occurs at 24-48hours after commencing vancomycin. If the concentration at steady state is not in therapeutic range (10-20 mg/L), the dose is adjusted and the concentration measured again 24 hour later. Using empiric vancomycin dosing regimens, fewer than 50% of infants achieve the target concentration at their first steady state level. Therefore once the dose is adjusted and concentration repeated, there is a delay of at least 48 hours before adequate antibiotic concentrations are achieved in the blood - delaying optimal treatment of life-threatening infections. This study aims to use early TDM and dose adjustment to improve the proportion of infants achieving target concentrations at their first steady-state level. Using a published population pharmacokinetic model, we identified a linear relationship between the first-dose trough and steady-state trough (R2 = 0.51) as well as the first-dose trough and AUC24 at 48 hours (R2= 0.70). This suggests that TDM could be performed after the first dose and that this early trough level could be used to predict the steady state level, enabling earlier dose adjustment and thereby shortening the time to effective therapy. This model has therefore been used to develop an online 'First-dose trough dose adjustment calculator'. In the VANC APP (Part 2)* study, participants will have individualised model-based intermittent vancomycin dosing using the Vanc App dosing calculator (as used in VANC APP Part 1, see clinicaltrials.gov ID: NCT04044703). A first-dose trough concentration will be measured for each participant and the clinician will then enter that concentration into the web application ('First-dose trough dose adjustment calculator'). A dose adjustment will be generated by the calculator if the predicted steady-state level is outside of target range. The vancomycin concentration is then measured at steady state to determine if the target concentration has been achieved. *Note: This study is 'part 2' of the VANC APP study protocol as approved under HREC reference number HREC/51942/RCHM-2019. Part 1 was registered separately on clinicaltrials.gov (clinicaltrials.gov ID: NCT04044703). Part 1 has been completed and assessed the use of model-based individualised intermittent vancomycin dosing using the Vanc App dosing calculator in 40 young infants aged 0 to 90 days. The vancomycin concentration was measured at steady state (24-48 hours) to determine the proportion of infants achieving target concentrations. Part 1 and part 2 are two separate studies and the results of each part will not be directly compared to one another.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis, Infections, Bacteremia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Vancomycin first-dose trough dose adjustment calculation
Arm Type
Experimental
Arm Description
Participants will have individualised model-based intermittent vancomycin dosing using the Vanc App dosing calculator (as used in VANC APP Part 1, see clinicaltrials.gov ID: NCT04044703). A first-dose trough concentration will be measured for each participant and the clinician will then enter that concentration into the web application ('First-dose trough dose adjustment calculator'). A dose adjustment will be generated by the calculator if the predicted steady-state level is outside of target range. If the predicted steady-state level is within target range (10-20mg/L) the calculator will recommend continuing with the same dose. The vancomycin concentration is then measured at steady state to determine if the target concentration has been achieved.
Intervention Type
Other
Intervention Name(s)
First-dose trough dose adjustment calculator - using early TDM (first-dose trough) to determine an early dose adjustment if the predicted steady-state trough is outside of target range (10-20mg/L)
Intervention Description
CALCULATOR: A 'First-dose trough dose adjustment calculator' was developed based on a population pharmacokinetic model. A participant's post-menstrual age, weight, creatinine, target trough concentration, dose, dosing interval and first-dose trough concentration (taken immediately before the second dose is due) are entered into the calculator. The calculator determines if a dose adjustment is required (based on whether the predicted steady-state trough concentration is <10mg/L or >20mg/L) and, if required, recommends a new adjusted dose.
Primary Outcome Measure Information:
Title
Target concentration at first steady-state concentration
Description
The proportion of young infants achieving target trough serum vancomycin concentrations (10 to 20 mg/L) at first steady-state level when model-based dosing is used followed by early therapeutic drug monitoring (and dose adjustment) after the first dose
Time Frame
From first vancomycin dose (immediately after consent) to steady state level taken at 24-48 hours post-first-dose
Secondary Outcome Measure Information:
Title
Sub- and supratherapeutic concentrations at first steady-state concentration
Description
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 when model-based dosing is used followed by early therapeutic drug monitoring (and dose adjustment) after the first dose
Time Frame
From first vancomycin dose (immediately after consent) to steady state level taken at 24-48 hours post-first-dose
Title
Drug-related adverse effects
Description
The frequency of drug-related adverse effects (infusion-related and nephrotoxicity).
Time Frame
From first vancomycin dose (immediately after consent) to completion of vancomycin therapy (as determined by clinical team, an average of 5 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
0 Days
Maximum Age & Unit of Time
90 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
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) Exclusion Criteria: Infants with a 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amanda Wilkins, MBBS
Phone
9345 5522
Email
amanda.wilkins@rch.org.au
First Name & Middle Initial & Last Name or Official Title & Degree
Amanda Gwee, MBBS
Phone
9345 5522
Email
amanda.gwee@rch.org.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amanda Wilkins, MBBS
Organizational Affiliation
Royal Children's Hospital Melbourne, Murdoch Children's Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royal Children's Hospital Melbourne
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amanda L Wilkins, MBBS
Phone
+61393455522
Email
amanda.wilkins@rch.org.au
First Name & Middle Initial & Last Name & Degree
Amanda L Wilkins, MBBS
Facility Name
Monash Newborn
City
Melbourne
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Atul Malhotra
Facility Name
Royal Hospital for Women
City
Sydney
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Srinivas Bolisetty
Facility Name
The Children's Hospital at Westmead
City
Sydney
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tony Lai

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Improving Therapeutic Drug Monitoring and Dosing for Vancomycin in Young Infants With Infections (VANCAPP) (Part 2)

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