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

Официальное название

Markers of Nephrotoxicity During Treatment With Antibiotic Combinations: A Pragmatic Clinical Trial

Обзор

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.

Вмешательства

• Препарат Vancomycin
  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 intraveno
• Препарат Piperacillin-tazobactam
  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
• Препарат Cefepime
  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

Первичные конечные точки

• Serum Cystatin C Concentration [Срок оценки: 5 days post enrollment]

Вторичные конечные точки (4)

• Kidney injury molecule 1 (KIM1) [Срок оценки: 5 days post enrollment]
• Serum creatinine concentration [Срок оценки: 5 days post enrollment]
• Acute Kidney Injury [Срок оценки: At 7 and 14 days]
• Major Adverse Kidney Events (MAKE) [Срок оценки: 30 and 60 days]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Pennsylvania Health System — Philadelphia

Публикации

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• Bellos I, Karageorgiou V, Pergialiotis V, Perrea DN. Acute kidney injury following the concurrent administration of antipseudomonal beta-lactams and vancomycin: a network meta-analysis. Clin Microbiol Infect. 2020 Jun;26(6):696-705. doi: 10.1016/j.cmi.2020.03.019. Epub 2020 Mar 25. PMID 32222460
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• Avedissian SN, Pais GM, Liu J, Rhodes NJ, Scheetz MH. Piperacillin-Tazobactam Added to Vancomycin Increases Risk for Acute Kidney Injury: Fact or Fiction? Clin Infect Dis. 2020 Jul 11;71(2):426-432. doi: 10.1093/cid/ciz1189. PMID 31833540
• Qian ET, Casey JD, Wright A, Wang L, Shotwell MS, Siemann JK, Dear ML, Stollings JL, Lloyd BD, Marvi TK, Seitz KP, Nelson GE, Wright PW, Siew ED, Dennis BM, Wrenn JO, Andereck JW, Han JH, Self WH, Semler MW, Rice TW; Vanderbilt Center for Learning Healthcare and the Pragmatic Critical Care Research Group. Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Ra PMID 37837651
• Miano TA, Hennessy S, Yang W, Dunn TG, Weisman AR, Oniyide O, Agyekum RS, Turner AP, Ittner CAG, Anderson BJ, Wilson FP, Townsend R, Reilly JP, Giannini HM, Cosgriff CV, Jones TK, Meyer NJ, Shashaty MGS. Association of vancomycin plus piperacillin-tazobactam with early changes in creatinine versus cystatin C in critically ill adults: a prospective cohort study. Intensive Care Med. 2022 Sep;48(9):1 PMID 35833959

Идентификаторы

NCT: NCT06954129 · 858301

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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