Continuous vs. Intermittent Infusion Vancomycin

Vancomycin Clinical Trial

Official title:

A Randomized Clinical Trial of Continuous vs. Intermittent Infusion Vancomycin: Effects on Measured GFR and Kidney Injury Biomarkers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05823116
• Other study ID #: 83412
• Secondary ID: R21AI176298
• Status: Recruiting
• Phase: Phase 4
• Start date: May 22, 2023
• Est. completion date: December 2024

Study information

• Verified date: May 2023
• Source: University of Kentucky
• Contact: Alexander H Flannery, PharmD, PhD
• Phone: 859-562-2766
• Email: alex.flannery[@]uky.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• = 18 years of age

• Hospitalized at University of Kentucky on a medical service (internal medicine or medical intensive care)

• Prescribed = 2 doses of vancomycin per treating physician

• Be able to provide written, informed consent, or have a legally authorized representative (LAR) responsible for their care able to provide written, informed consent.

Exclusion Criteria:

• Chronic kidney disease (documented or prior to admission estimated GFR (eGFR) <60 ml/min/1.73m2 using non-race-based creatinine GFR equation)

• End stage kidney disease

• Stage 1 or higher AKI per Kidney Disease: Improving Global Outcomes (KDIGO) classification (serum creatinine increase = 0.3 mg/dl or 1.5-1.9 times baseline; urine output < 0.5 ml/kg/hr for 6-12 hours)

• Receipt of vancomycin within the last 72 hours (not considering the loading dose)

• Allergy to iohexol

• Uroepithelial tumors

• Pregnancy

• Prisoner

Related Conditions & MeSH terms

• Vancomycin

Intervention

Drug:
• Vancomycin Continuous Infusion
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.
• Vancomycin Intermittent Infusion
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.

Locations

Country	Name	City	State
United States	University of Kentucky	Lexington	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Alexander Flannery	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in measured glomerular filtration rate (GFR)	measured via the administration of a small dose of iohexol followed by the collection of blood samples	Baseline (Day 0) and Day 3
Primary	Change in urinary Kidney Injury Molecule 1 (KIM-1)	Measured by urine ELISA test as the change score	Baseline (Day 0) and Day 3
Secondary	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.	Baseline up to 5 days
Secondary	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.	Baseline up to 5 days
Secondary	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.	Baseline up to 5 days
Secondary	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.	Baseline up to 5 days
Secondary	Change in Urine Kidney Injury Molecule-1 (KIM-1)	Measured as the change score, only in the only in subset of patients prescribed 5 or more days of vancomycin	Baseline (Day 0) and Day 5
Secondary	Vancomycin Area-Under-the-Curve (AUC) target attainment	Defined as range 400-600 mg*hr/L. AUC assessed using one concentration Bayesian estimates.	Day 1
Secondary	Acute Kidney Injury (AKI) over time	Using serum creatinine and urine output components of Kidney Disease: Improving Global Outcome (KIDGO) classification	Daily up to 10 days
Secondary	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.	Daily up to 7 days
Secondary	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.	Daily up to 7 days
Secondary	Acute Kidney Disease	measured per Acute Disease Quality Initiative (ADQI) criteria in a subset of participants where AKI does not resolve by 7 days	Until hospital discharge, up to 17 days
Secondary	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.	Until hospital discharge, up to 17 days
Secondary	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	Baseline (Day 0) and Day 5