Improving Dosing of Vancomycin in Young Infants With Infections

NCT ID: NCT04044703

Last Updated: 2021-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-30
• Study Completion Date: 2021-01-03

Brief Summary

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.

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.

Conditions

Sepsis; Infection; Bacteremia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Vancomycin - model-based dosing regimen

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: DRUG

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)
• 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

• Minimum Eligible Age: 0 Days
• Maximum Eligible Age: 90 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Royal Children's Hospital

OTHER

Sponsor Role: collaborator

Royal Hospital For Women

OTHER

Sponsor Role: collaborator

University of Otago

OTHER

Sponsor Role: collaborator

Sydney Children's Hospitals Network

OTHER

Sponsor Role: collaborator

Monash Health

OTHER

Sponsor Role: collaborator

Murdoch Childrens Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Amanda Wilkins

Paediatric trainee

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amanda Wilkins, MBBS

Role: PRINCIPAL_INVESTIGATOR

Murdoch Childrens Research Institute

Locations

Royal Hospital for Women

Sydney, New South Wales, Australia

Children's Hospital at Westmead

Sydney, New South Wales, Australia

Royal Children's Hospital Melbourne

Melbourne, Victoria, Australia

Monash Children's Hospital

Melbourne, Victoria, Australia

Countries

Australia

Other Identifiers

HREC2019.059

Identifier Type: -

Identifier Source: org_study_id