The Vancomycin Piperacillin/Tazobactam (VPT) Patient Safety Trial (VPS)

Официальное название

A Randomized Controlled Trial Comparing Renal Effects of Vancomycin Combined With Either Piperacillin/Tazobactam or Meropenem: VPT Patient Safety (VPS) Study

Обзор

The VPT Safety Trial (VPS) compares two common antibiotic combinations to see how they affect the kidneys of patients in the hospital with serious infections. Both combinations are approved by the Food and Drug Administration (FDA). The goal is to help doctors know which combination is safer so they can make better choices for their patients.

Подробное описание

* What is the study's main question? Does the antibiotic combination vancomycin and piperacillin/tazobactam (VPT) cause kidney problems (acute kidney injury or AKI)? * What is the Background to the Research Question? VPT is the most common antibiotic combination used for patients in the hospital with serious infections. Some studies using a standard kidney blood test (creatinine) show more kidney problems (AKI) with VPT than with other antibiotic combinations, but these studies are not always very accurate. Because of this, some doctors use other combinations like vancomycin and cefepime (VC) or vancomycin and meropenem (VM). However, these other combinations may have their own risks, like infections that are hard to treat, serious diarrhea, higher cost, or problems with the brain. One study used a better kidney blood test (cystatin C) and did not find more kidney problems with VPT. Another more accurate type of study (randomized clinical trial) also did not find more kidney problems with VPT, but some people did not agree with how that study was done. So, doctors are still not sure if VPT causes more kidney problems, or if they should use VPT or another antibiotic combination for patients in the hospital with serious infections. * Why is AKI important? AKI is important because people who get it may have more heart and kidney problems, might need dialysis, stay in the hospital longer, have more hospital visits, higher costs, and a higher chance of death. Avoiding AKI can help prevent these problems. * How will this study help answer the question? VPS is a randomized study, which is usually more accurate, and uses a better kidney function blood test (cystatin C). The results will help doctors make better guidelines, improve care, and keep patients safer. * What are the goals of VPS? The main goal is to find out if VPT really causes kidney problems, so doctors can choose the best antibiotics for patients with serious infections. The study will look at differences in a special kidney blood test (cystatin C) between patients getting VPT and those getting VM. Other goals are to compare things like kidney problems, infections, how long patients stay in the hospital, repeat hospital visits, if patients need a breathing machine or medicine for low blood pressure, quality of life, and death rates.

Вмешательства

• Препарат Piperacillin + Tazobactam
  PT Dosing (concealed): PT dosing is standard irrespective of infection severity. 4.5 gm IV loading dose over 30 min, then 4.5 g IV over 4 hr (extended infusion) 6 hrs after the loading dose, and then q 8 hr
• Препарат meropenem
  M dosing (concealed): M dosing depends on infection severity. 1 gm loading IV dose over 30 min, then 1 gm IV over 4 hr (extended infusion) q 8 hr (default dosing). Clinician has option to increase to 2 gm IV q 8 hr for severe infections and to decrease back to default dosing if previously chosen higher dosing is no longer deemed indicated.

Первичные конечные точки

• Serum cystatin C (Scys) [Срок оценки: 7 days]

Вторичные конечные точки (2)

• Acute Kidney injury (AKI)/death [Срок оценки: 7 days]
• Infectious complications [Срок оценки: 90 days]

Критерии участия

Критерии включения

• Hospitalized or being hospitalized.
• Age >/=18 yr old.
• Serious or suspected serious infection for which VPT or VM considered a broad-spectrum combination antibiotic backbone standard of care by clinician.
• Enrollment can be completed before the first dose of abx (ideally) and no later than before the second dose (alternatively).
• Consenting/enrollment will not clinically significantly delay abx administration.
• Baseline and >/=1 prior Scr available (within 1 yr).
• Pt or LAR able to provide IC. Exclusion criteria

1\. AKI (>/=moderate) (KDIGO stage 2-3) (Scr increase >/=2-fold from chronic BL) (Scr based).

2\. CKD (>/=moderately to severely decreased eGFR) (KDIGO stage G3b-G5) (by history or eGFR </=44 mL/min/1.73M2) (Scr based).

3\. Beta lactam allergy. 4. Contraindication to VPT or VM. 5. Infection requiring VPT or VM specifically or another abx regimen. 6. Participation in another research study with interventions that may impact study endpoints.

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

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Bassett Medical Center — Cooperstown

Публикации

• 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
• Rahman M, Shad F, Smith MC. Acute kidney injury: a guide to diagnosis and management. Am Fam Physician. 2012 Oct 1;86(7):631-9. PMID 23062091
• Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005 Apr 2-8;365(9466):1231-8. doi: 10.1016/S0140-6736(05)74811-X. PMID 15811456
• FDA. Pfizer Injectables. ZOSYN (piperacillin and tazobactam) for injection. 2017. Accessed November 12, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/050684s88s89s90_050750s37s38s39lbl.pdf
• 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
• Cote JM, Desjardins M, Murray PT. Does Vancomycin-Piperacillin-Tazobactam Cause Pseudo-AKI, True Nephrotoxicity, or Both? Chest. 2023 Aug;164(2):273-274. doi: 10.1016/j.chest.2023.05.009. No abstract available. PMID 37558318
• Blair M, Cote JM, Cotter A, Lynch B, Redahan L, Murray PT. Nephrotoxicity from Vancomycin Combined with Piperacillin-Tazobactam: A Comprehensive Review. Am J Nephrol. 2021;52(2):85-97. doi: 10.1159/000513742. Epub 2021 Mar 18. PMID 33735856
• Kimball JM, Deri CR, Nesbitt WJ, Nelson GE, Staub MB. Development of the Three Antimicrobial Stewardship E's (TASE) Framework and Association Between Stewardship Interventions and Intended Results Analysis to Identify Key Facility-Specific Interventions and Strategies for Successful Antimicrobial Stewardship. Clin Infect Dis. 2021 Oct 20;73(8):1397-1403. doi: 10.1093/cid/ciab430. PMID 33983389

Идентификаторы

NCT: NCT07556107 · IRB00538615 · BPS-2024C3-42018

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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