A Pragmatic Clinical Trial Comparing the Risk of Acute Kidney Injury During Treatment With Vancomycin and Piperacillin-Tazobactam vs. Vancomycin and Cefepime in Hospitalized Patients
- Conditions
- Acute Kidney Injury
- Interventions
- Registration Number
- NCT06954129
- Lead Sponsor
- University of Pennsylvania
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 750
- Age of at least 18 years
- Suspected or confirmed infection based on clinical criteria, for which vancomycin with piperacillin-tazobactam or vancomycin with cefepime was prescribed by the treating clinician, as evidenced by orders being placed in the electronic health record
- The treating clinician considers both vancomycin with piperacillin- tazobactam or vancomycin with cefepime as acceptable treatment
- The treating clinician anticipates at least 48 hours of antibiotic treatment
- Dialysis dependence or documented end stage kidney disease
- AKI at baseline
- Expected survival <24 hours and/or presence of do not resuscitate orders
- History of antibiotic-resistant organisms (microbiological culture results showing bacterial isolates with resistant or intermediate susceptibility to any study drug within the prior 90 days)
- Documented allergy to vancomycin, cephalosporins, or penicillin
- Suspected central nervous system infection
- Inability to provide informed consent or lack of proxy for consent
- Prisoners/incarcerated individuals
- Known pregnancy or breastfeeding
- Previous enrollment in this study
- Receipt of vancomycin, piperacillin-tazobactam, or cefepime for >24 hours within the preceding 7 days. At the time of screening, one-time doses of vancomycin, with or without piperacillin-tazobactam, or cefepime, will be allowed prior to randomization to avoid treatment delays; such patients must be enrolled within twelve hours of antibiotic administration.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vancomycin with Cefepime Vancomycin Participants in the Vancomycin with Cefepime arm will be randomized to initial treatment with Vancomycin with Cefepime. Subsequent management of antimicrobial treatment will be at the discretion of treating clinicians Vancomycin with Cefepime Cefepime Participants in the Vancomycin with Cefepime arm will be randomized to initial treatment with Vancomycin with Cefepime. Subsequent management of antimicrobial treatment will be at the discretion of treating clinicians Vancomycin with Piperacillin-Tazobactam Vancomycin Participants in the Vancomycin with Piperacillin-Tazobactam arm will be randomized to initial treatment with Vancomycin with Piperacillin-Tazobactam. Subsequent management of antimicrobial treatment will be at the discretion of treating clinicians Vancomycin with Piperacillin-Tazobactam Piperacillin-tazobactam Participants in the Vancomycin with Piperacillin-Tazobactam arm will be randomized to initial treatment with Vancomycin with Piperacillin-Tazobactam. Subsequent management of antimicrobial treatment will be at the discretion of treating clinicians
- Primary Outcome Measures
Name Time Method Serum Cystatin C Concentration 5 days post enrollment Change in serum cystatin c concentration through Day 5 after antibiotic initiation.
- Secondary Outcome Measures
Name Time Method Kidney injury molecule 1 (KIM1) 5 days post enrollment Changes in urinary KIM1 concentration through Day 5 after antibiotic initiation.
Serum creatinine concentration 5 days post enrollment Change in serum creatinine concentration through Day 5 after antibiotic initiation.
Acute Kidney Injury At 7 and 14 days 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))Major Adverse Kidney Events (MAKE) 30 and 60 days MAKE consists of death, need for RRT, or persistent kidney dysfunction (decrease in estimated glomerular filtration rate (GFR) to \<75% of baseline)