A Randomized Clinical Trial of Continuous vs. Intermittent Infusion Vancomycin: Effects on Measured GFR and Kidney Injury Biomarkers
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Change in measured glomerular filtration rate (GFR)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 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.
排除标准
- •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
研究组 & 干预措施
Vancomycin continuous infusion
Continuous infusion of Vancomycin
干预措施: Vancomycin Continuous Infusion (Drug)
Vancomycin intermittent infusion
Intermittent infusion of vancomycin
干预措施: Vancomycin Intermittent Infusion (Drug)
结局指标
主要结局
Change in measured glomerular filtration rate (GFR)
时间窗: Baseline (Day 0) and Day 3
measured via the administration of a small dose of iohexol followed by the collection of blood samples
Change in urinary Kidney Injury Molecule 1 (KIM-1)
时间窗: Baseline (Day 0) and Day 3
Measured by urine ELISA test as the change score
次要结局
- Acute Kidney Disease(Until hospital discharge, up to 17 days)
- Plasma cystatin C over time(Baseline up to 5 days)
- Phlebitis over time(Daily up to 7 days)
- Infiltration over time(Daily up to 7 days)
- Urine Clusterin over time(Baseline up to 5 days)
- Urine Osteopontin over time(Baseline up to 5 days)
- Vancomycin Area-Under-the-Curve (AUC) target attainment(Day 1)
- Acute Kidney Injury (AKI) over time(Daily up to 10 days)
- Number of Participants with Major Adverse Kidney Events(Until hospital discharge, up to 17 days)
- Change in Urine Kidney Injury Molecule-1 (KIM-1)(Baseline (Day 0) and Day 5)
- Urine Kidney Injury Molecule-1 (KIM-1) over time(Baseline up to 5 days)
- Change in measured glomerular filtration rate (GFR)(Baseline (Day 0) and Day 5)
研究者
Aaron Cook
Associate Professor
University of Kentucky