Hospitalized patients with suspected or confirmed infection are commonly treated with vancomycin (VN) in combination with either piperacillin-tazobactam (PT) or cefepime (CP). Although these regimens have similar effectiveness, recent observational evidence suggests they may differ in terms of the risk for acute kidney injury (AKI). Interpretation of existing evidence is complicated by the limitations of creatinine, the standard biomarker used to monitor kidney function, which has poor sensitivity and specificity for drug induced AKI. To address this important knowledge gap, the investigators propose to conduct a pragmatic, open-label, non-inferiority trial that will examine the comparative risk of AKI between these standard-of-care antibiotic combinations using sensitive and specific markers of drug-induced AKI. We hypothesize that the regimen of VN in combination with PT (VN+PT) is noninferior to the regimen of VN in combination with CP (VN+CP) in terms of AKI risk.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
750
Vancomycin is a glycopeptide antibiotic used to treat infections caused by Gram-positive bacteria, including those due to methicillin-resistant Staphylococcus aureus. Dosing of vancomycin will follow standard of care procedures, including the use of individualized dosing regimens developed in consultation with clinical pharmacists, based on participant body weight and renal function, and dosage titration guided by therapeutic drug monitoring. Vancomycin is administered via intermittent intravenous infusions of 60-90 minutes.
Piperacillin-tazobactam is an anti-pseudomonal penicillin with a dose range of 2.25 g or 4.5 g and frequency of every 6 or 8 hours based on a participant's body weight, renal function, and clinician discretion. Piperacillin-tazobactam is administered via extended-duration (4 hours) intravenous infusions
Cefepime is an anti-pseudomonal cephalosporin with a dose range of 500 mg, 1,000 mg, or 2,000 mg, and frequency every 8, 12, or 24 hours based on a participant's body weight, renal function, and clinician discretion. Cefepime is administered via extended-duration (4 hours) intravenous infusions
University of Pennsylvania Health System
Philadelphia, Pennsylvania, United States
RECRUITINGSerum Cystatin C Concentration
Change in serum cystatin c concentration through Day 5 after antibiotic initiation.
Time frame: 5 days post enrollment
Kidney injury molecule 1 (KIM1)
Changes in urinary KIM1 concentration through Day 5 after antibiotic initiation.
Time frame: 5 days post enrollment
Serum creatinine concentration
Change in serum creatinine concentration through Day 5 after antibiotic initiation.
Time frame: 5 days post enrollment
Acute Kidney Injury
Acute kidney injury as defined by Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria: Stage 1 AKI (Creatinine increase by 1.5-1.9 times baseline OR increase by \>= 0.3 mg/dL) Stage 2 AKI (Creatinine increase by 2.0-2.9 times baseline) Stage 3 AKI (Creatinine increase by \>= 3.0 times baseline OR increase to \>= 4.0 mg/dL OR New renal replacement therapy (RRT))
Time frame: At 7 and 14 days
Major Adverse Kidney Events (MAKE)
MAKE consists of death, need for RRT, or persistent kidney dysfunction (decrease in estimated glomerular filtration rate (GFR) to \<75% of baseline)
Time frame: 30 and 60 days
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