RCT of Continuous Versus Intermittent Infusion of Vancomycin in Neonates

Study Overview
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Brief Summary
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Babies aged 0 to 90 days with a suspected infection requiring treatment with vancomycin will be recruited. They will be randomised to receive vancomycin as an intermittent infusion (over 1 hour) or as a continuous infusion (over 24 hours). The hypothesis is that administering vancomycin as a continuous infusion will result in improved attainment of target concentrations in blood at steady state (when the drug is in equilibrium) compared to intermittent infusion.

Official Title
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A Randomised Controlled Trial (RCT) of Continuous and Intermittent Infusion of Vancomycin in Neonates

Conditions
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Sepsis, Infection, Bacteremia

Intervention / Treatment
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* Drug: Continuous infusion of vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Neonates in the neonatal unit with an infection requiring treatment with vancomycin as determined by the treating physician. Exclusion Criteria: Infants with a corrected gestational age < 25 weeks. Allergy to vancomycin or other glycopeptide antibiotic Vancomycin administered within the previous 72 hours Renal impairment Prior enrolment in the study Need for drug that is incompatible with vancomycin (if no other IV line is available)

Ages Eligible for Study
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Maximum Age: 90 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Intermittent infusion of vancomycin<br>Vancomycin will be administered intravenously over 1 hour. Doses will be given from one to four times a day according to corrected gestational age. | |
| Active Comparator: Continuous infusion of vancomycin<br>A loading dose of vancomycin will be given over 1 hour followed by a continuous infusion of vancomycin over a 24 hour period. | Drug: Continuous infusion of vancomycin<br>* Continuous infusion of vancomycin will be given as a loading dose over 1 hour then as a continuous infusion over a 24-hours period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of neonates achieving target vancomycin concentrations in blood at steady state (24-48 hours) |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug-related adverse effects | the proportion of drug-related adverse effects with CIV compared to IIV | 2 years | 
| Time to achieve target levels | the time to and number of dose adjustments required to achieve target therapeutic vancomycin levels in blood | 2 years | 
| Clearance of vancomycin in young infants | Population pharmacokinetic modelling of vancomycin in young infants using NONMEM | 2 years | 
| Volume of distribution of vancomycin in young infants | Population pharmacodynamics modelling of vancomycin in young infants using NONMEM | 2 years | 
| Area under the concentration-time curve of vancomycin in young infants | Population pharmacodynamics modelling of vancomycin in young infants using NONMEM | 2 years | 
| Time above the minimum inhibitory concentration of the bacteria for vancomycin in young infants | Population pharmacodynamics modelling of vancomycin in young infants using NONMEM | 2 years |