Markers of Nephrotoxicity During Treatment With Antibiotic Combinations: A Pragmatic Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 750
- 试验地点
- 1
- 主要终点
- Serum Cystatin C Concentration
研究概览
简要总结
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.
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
- •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
排除标准
- •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.
研究组 & 干预措施
Vancomycin with 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
干预措施: Vancomycin (Drug)
Vancomycin with 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
干预措施: Piperacillin-tazobactam (Drug)
Vancomycin with 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
干预措施: Vancomycin (Drug)
Vancomycin with 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
干预措施: Cefepime (Drug)
结局指标
主要结局
Serum Cystatin C Concentration
时间窗: 5 days post enrollment
Change in serum cystatin c concentration through Day 5 after antibiotic initiation.
次要结局
- Kidney injury molecule 1 (KIM1)(5 days post enrollment)
- Serum creatinine concentration(5 days post enrollment)
- Acute Kidney Injury(At 7 and 14 days)
- Major Adverse Kidney Events (MAKE)(30 and 60 days)
研究者
Todd Miano
Assistant Professor of Epidemiology
University of Pennsylvania