Clinical trial NCT05823116: Continuous vs. Intermittent Infusion Vancomycin
Official title: A Randomized Clinical Trial of Continuous vs. Intermittent Infusion Vancomycin: Effects on Measured GFR and Kidney Injury Biomarkers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Vancomycin
Keywords: Infusion
Adverse Effect
Acute Kidney Injury
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2023-04-21
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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)
* Greater than 2 doses of vancomycin within the last 72 hours
* Allergy to iohexol
* Uroepithelial tumors
* Pregnancy
* Prisoner

Primary outcomes:
measure: Change in measured glomerular filtration rate (GFR)
timeFrame: Baseline (Day 0) and Day 3
measure: Change in urinary Kidney Injury Molecule 1 (KIM-1)
timeFrame: Baseline (Day 0) and Day 3
Secondary outcomes:
measure: Plasma cystatin C over time
timeFrame: Baseline up to 5 days
measure: Urine Clusterin over time
timeFrame: Baseline up to 5 days
measure: Urine Osteopontin over time
timeFrame: Baseline up to 5 days
measure: Urine Kidney Injury Molecule-1 (KIM-1) over time
timeFrame: Baseline up to 5 days
measure: Change in Urine Kidney Injury Molecule-1 (KIM-1)
timeFrame: Baseline (Day 0) and Day 5
measure: Vancomycin Area-Under-the-Curve (AUC) target attainment
timeFrame: Day 1
measure: Acute Kidney Injury (AKI) over time
timeFrame: Daily up to 10 days
measure: Phlebitis over time
timeFrame: Daily up to 7 days
measure: Infiltration over time
timeFrame: Daily up to 7 days
measure: Acute Kidney Disease
timeFrame: Until hospital discharge, up to 17 days
measure: Number of Participants with Major Adverse Kidney Events
timeFrame: Until hospital discharge, up to 17 days
measure: Change in measured glomerular filtration rate (GFR)
timeFrame: Baseline (Day 0) and Day 5
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Aaron M Cook, PharmD
role: PRINCIPAL_INVESTIGATOR
References: