Hospitalized adult participants prescribed vancomycin by their treating physician will be randomized to receive vancomycin via continuous or intermittent infusion and measures of kidney function and injury will be collected.
All study participants regardless of participation status will have been prescribed vancomycin by a treating physician and received a dose per institutional standard of care. Participants will be randomized 1:1 in permuted blocks of 2, 4, or 6 to receive subsequent doses via continuous or intermittent infusion. Participants randomized to intermittent infusion will receive doses per standard of care at infusion rates of 1 gram per hour in every 8,-12, or -24 hour intervals, while participants randomized to continuous infusion will receive a total daily dose infused over a period of 24 hours. Vancomycin concentration will not exceed 5mg/ml and will be infused via central (preferred) or peripheral administration. In order to ensure consistent dosing between study arms, a precision dosing platform will be used by the PI and team to determine total daily doses to best target an AUC of 500 mg x hr/L (range 400-600 mg x hr/L). A single vancomycin concentration will be obtained the following day with Bayesian-guided area-under-the-curve (AUC) monitoring (with dosing adjusted if needed) to ensure vancomycin exposure remains similar between infusion strategies. Both the initiation and discontinuation of vancomycin, as well as any additional therapeutic drug monitoring, will remain at the discretion of the primary clinical team. Glomerular filtration rate (GFR) will be measured on the day of enrollment and day 3 by the administration of 5 ml iohexol (300 mgI/ml) with iohexol plasma concentrations obtained 1 and 4 hours following administration of iohexol. This change in measured GFR between the infusion strategies is the primary outcome of the study. Plasma and urinary markers of kidney function and injury will be obtained the day of enrollment (Day 0) and subsequent days (Days 2-3). If the participant remains on vancomycin 120 hours following enrollment, measured glomerular filtration rate (mGFR) and biomarkers will be assessed again.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
37
A precision drug dosing platform will be used to determine the empiric dosing regimen and the dosing parameter targeted will be an area-under-the-curve (AUC) of 500 mg⸱hr/L (range 400-600 mg⸱hr/L). The total daily dose is infused over a period of 24 hours.
A precision drug dosing platform will be used to determine the empiric dosing regimen and the dosing parameter targeted will be an area-under-the-curve (AUC) of 500 mg⸱hr/L (range 400-600 mg⸱hr/L). The dose is infused at rates of 1 gram per hour in every 8, -12, or -24 hour intervals.
University of Kentucky
Lexington, Kentucky, United States
Change in measured glomerular filtration rate (GFR)
measured via the administration of a small dose of iohexol followed by the collection of blood samples
Time frame: Baseline (Day 0) and Day 3
Change in urinary Kidney Injury Molecule 1 (KIM-1)
Measured by urine ELISA test as the change score
Time frame: Baseline (Day 0) and Day 3
Plasma cystatin C over time
Measured by urine ELISA test at baseline, 48-, and 72-hours following the first dose of vancomycin. Additional measure at 120 hours if the patient is prescribed vancomycin for 120 hours or more.
Time frame: Baseline up to 5 days
Urine Clusterin over time
Measured by urine ELISA test at baseline, 48-, and 72-hours following the first dose of vancomycin. Additional measure at 120 hours if the patient is prescribed vancomycin for 120 hours or more.
Time frame: Baseline up to 5 days
Urine Osteopontin over time
Measured by urine ELISA test at baseline, 48-, and 72-hours following the first dose of vancomycin. Additional measure at 120 hours if the patient is prescribed vancomycin for 120 hours or more.
Time frame: Baseline up to 5 days
Urine Kidney Injury Molecule-1 (KIM-1) over time
Measured by urine ELISA test test at baseline, 48-, and 72-hours following the first dose of vancomycin. Additional measure at 120 hours if the patient is prescribed vancomycin for 120 hours or more.
Time frame: Baseline up to 5 days
Change in Urine Kidney Injury Molecule-1 (KIM-1)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Measured as the change score, only in the only in subset of patients prescribed 5 or more days of vancomycin
Time frame: Baseline (Day 0) and Day 5
Vancomycin Area-Under-the-Curve (AUC) target attainment
Defined as range 400-600 mg\*hr/L. AUC assessed using one concentration Bayesian estimates.
Time frame: Day 1
Acute Kidney Injury (AKI) over time
Using serum creatinine and urine output components of Kidney Disease: Improving Global Outcome (KIDGO) classification
Time frame: Daily up to 10 days
Phlebitis over time
Monitored per standard of care, using phlebitis scores of 0 (no clinical symptoms) to 4. Documented scores above 0 will be classified as phlebitis.
Time frame: Daily up to 7 days
Infiltration over time
Monitored per standard of care, using infiltration scores of 0 (no clinical symptoms) to 4. Documented scores above 0 will be classified as infiltration.
Time frame: Daily up to 7 days
Acute Kidney Disease
measured per Acute Disease Quality Initiative (ADQI) criteria in a subset of participants where AKI does not resolve by 7 days
Time frame: Until hospital discharge, up to 17 days
Number of Participants with Major Adverse Kidney Events
Composite of death, requirement for kidney replacement therapy, or reduction of 25% from baseline estimated glomerular filtration rate.
Time frame: Until hospital discharge, up to 17 days
Change in measured glomerular filtration rate (GFR)
measured via the administration of a small dose of iohexol followed by the collection of blood samples, only in the subset of patients receiving vancomycin for 5 days
Time frame: Baseline (Day 0) and Day 5