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Improving Therapeutic Drug Monitoring and Dosing for Vancomycin in Young Infants with Infections (VANCAPP) (Part 2)
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.
Study details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 0 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2024-11-30
Primary completion: 2025-08-01
Study completion finish: 2025-12-01
Study type
TREATMENT
Phase
PHASE4
Trial ID
NCT05770622
Intervention or treatment
OTHER: 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)
Conditions
- • Sepsis
- • Infections
- • Bacteremia
Condition: Sepsis, Infections and more
OTHER: 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)
Melbourne, Victoria, Australia and more
Sponsor: Murdoch Childrens Research Institute
Find a site
Closest Location:
Royal Children's Hospital Melbourne
Research sites nearby
Select from list below to view details:
Royal Children's Hospital Melbourne
Melbourne, Victoria, Australia
Monash Newborn
Melbourne, Not Specified, Australia
Royal Hospital for Women
Sydney, Not Specified, Australia
The Children's Hospital at Westmead
Sydney, Not Specified, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Vancomycin first-dose trough dose adjustment calculation
| OTHER: 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)
|
What is the study measuring?
Primary outcome
| Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
|---|---|---|
| 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 | From first vancomycin dose (immediately after consent) to steady state level taken at 24-48 hours post-first-dose |
Secondary outcome
| Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
|---|---|---|
| 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 | From first vancomycin dose (immediately after consent) to steady state level taken at 24-48 hours post-first-dose |
| Drug-related adverse effects | The frequency of drug-related adverse effects (infusion-related and nephrotoxicity). | From first vancomycin dose (immediately after consent) to completion of vancomycin therapy (as determined by clinical team, an average of 5 days) |
Frequently Asked Questions
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