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| ID | Type | Description | Link |
|---|---|---|---|
| BPS-2024C3-42018 | Other Grant/Funding Number | PCORI |
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| Name | Class |
|---|---|
| Johns Hopkins University | OTHER |
| Patient-Centered Outcomes Research Institute | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Piperacillin/tazobactam | Active Comparator | Vancomycin plus piperacillin/tazobactam |
|
| Meropenem | Active Comparator | Vancomycin plus meropenem |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Piperacillin + Tazobactam | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Serum cystatin C (Scys) | Difference between highest Scys (mg/L) post-treatment over 7 days minus Scys pre-treatment, expressed as ratio of pre-treatment level | 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| Acute Kidney injury (AKI)/death | AKI/death KDIGO ADQI stages 0-4 (expanded with injury biomarkers) (Scr-Scys, Scys, Scr based) (transient <72 vs. persistent >72 hr) rate | 7 days |
| Infectious complications |
| Measure | Description | Time Frame |
|---|---|---|
| serum creatinine (Scr) | Difference between highest Scr (mg/L) post-treatment over 7 D minus Scr pre-treatment, expressed as ratio of pre-treatment level | 7 days |
| Kidney Injury biomarkers | NGAL, TIMP-2×IGFBP7, KIM-1, ACR |
Inclusion 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 \
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Amanda Hasuly | Contact | 443-473-0986 | amanda.hasuly@bassett.org | |
| Jennifer Victory | Contact | 607-547-6965 | jennifer.victory@bassett.org |
| Name | Affiliation | Role |
|---|---|---|
| Daniel Freilich, MD | Bassett Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bassett Medical Center | Cooperstown | New York | 13326 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35833959 | Background | 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):1144-1155. doi: 10.1007/s00134-022-06811-0. Epub 2022 Jul 14. | |
| 23062091 |
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| ID | Term |
|---|---|
| D007239 | Infections |
| D058186 | Acute Kidney Injury |
| D018805 | Sepsis |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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Not provided
| ID | Term |
|---|---|
| D000077725 | Piperacillin, Tazobactam Drug Combination |
| D000077731 | Meropenem |
| ID | Term |
|---|---|
| D000078142 | Tazobactam |
| D010397 | Penicillanic Acid |
| D010406 | Penicillins |
| D047090 | beta-Lactams |
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Comparative Effectiveness (safety) Research, mRCT, standard care treatment/control, parallel group, quadruple-blinded, pragmatic, adaptive (sample size reassessment), noninferiority, and individual level randomization.
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| meropenem | Drug | 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. |
|
MDR (MRSA, VRE, ESBL, CRE)/fungal/CDI rate
| 90 days |
| 90 days |
| Background |
| 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. |
| 15811456 | Background | 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. |
| Background | 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 |
| 37837651 | Background | 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 Randomized Clinical Trial. JAMA. 2023 Oct 24;330(16):1557-1567. doi: 10.1001/jama.2023.20583. |
| 37558318 | Background | 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. |
| 33735856 | Background | 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. |
| 33983389 | Background | 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. |
| 29507935 | Background | Downes KJ, Laskin BL, Fisher BT. The Cost of Vancomycin and Piperacillin/Tazobactam Treatment-Reply. JAMA Pediatr. 2018 May 1;172(5):494-495. doi: 10.1001/jamapediatrics.2018.0038. No abstract available. |
| 32421195 | Background | Goodman KE, Cosgrove SE, Pineles L, Magder LS, Anderson DJ, Dodds Ashley E, Polk RE, Quan H, Trick WE, Woeltje KF, Leekha S, Harris AD. Significant Regional Differences in Antibiotic Use Across 576 US Hospitals and 11 701 326 Adult Admissions, 2016-2017. Clin Infect Dis. 2021 Jul 15;73(2):213-222. doi: 10.1093/cid/ciaa570. |
| 37040818 | Background | Chen AY, Deng CY, Calvachi-Prieto P, Armengol de la Hoz MA, Khazi-Syed A, Chen C, Scurlock C, Becker CD, Johnson AEW, Celi LA, Dagan A. A Large-Scale Multicenter Retrospective Study on Nephrotoxicity Associated With Empiric Broad-Spectrum Antibiotics in Critically Ill Patients. Chest. 2023 Aug;164(2):355-368. doi: 10.1016/j.chest.2023.03.046. Epub 2023 Apr 9. |
| 35982631 | Background | Alosaimy S, Lagnf AM, Hobbs ALV, Mubarez M, Kufel WD, Morrisette T, Polisetty RS, Li D, Veve MP, Simon SP, Truong J, Finch N, Venugopalan V, Rico M, Amaya L, Yost C, Cubillos A, Chandler E, Patch M, Smith IMK, Biagi M, Wrin J, Moore WJ, Molina KC, Rebold N, Holger D, Kunz Coyne AJ, Jorgensen SCJ, Witucki P, Tran NN, Davis SL, Sakoulas G, Rybak MJ. Nephrotoxicity of Vancomycin in Combination With Beta-Lactam Agents: Ceftolozane-Tazobactam vs Piperacillin-Tazobactam. Clin Infect Dis. 2023 Feb 8;76(3):e1444-e1455. doi: 10.1093/cid/ciac670. |
| 26952639 | Background | Hammond DA, Smith MN, Painter JT, Meena NK, Lusardi K. Comparative Incidence of Acute Kidney Injury in Critically Ill Patients Receiving Vancomycin with Concomitant Piperacillin-Tazobactam or Cefepime: A Retrospective Cohort Study. Pharmacotherapy. 2016 May;36(5):463-71. doi: 10.1002/phar.1738. Epub 2016 Apr 1. |
| 27805728 | Background | Giuliano CA, Patel CR, Kale-Pradhan PB. Is the Combination of Piperacillin-Tazobactam and Vancomycin Associated with Development of Acute Kidney Injury? A Meta-analysis. Pharmacotherapy. 2016 Dec;36(12):1217-1228. doi: 10.1002/phar.1851. Epub 2016 Nov 28. |
| 27940946 | Background | Hammond DA, Smith MN, Li C, Hayes SM, Lusardi K, Bookstaver PB. Systematic Review and Meta-Analysis of Acute Kidney Injury Associated with Concomitant Vancomycin and Piperacillin/tazobactam. Clin Infect Dis. 2017 Mar 1;64(5):666-674. doi: 10.1093/cid/ciw811. Epub 2016 Dec 10. |
| 32222460 | Background | 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. |
| 25291579 | Background | Magill SS, Edwards JR, Beldavs ZG, Dumyati G, Janelle SJ, Kainer MA, Lynfield R, Nadle J, Neuhauser MM, Ray SM, Richards K, Rodriguez R, Thompson DL, Fridkin SK; Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team. Prevalence of antimicrobial use in US acute care hospitals, May-September 2011. JAMA. 2014 Oct 8;312(14):1438-46. doi: 10.1001/jama.2014.12923. |
| 29020249 | Background | Watkins RR, Deresinski S. Increasing Evidence of the Nephrotoxicity of Piperacillin/Tazobactam and Vancomycin Combination Therapy-What Is the Clinician to Do? Clin Infect Dis. 2017 Nov 29;65(12):2137-2143. doi: 10.1093/cid/cix675. |
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007769 |
| Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D010878 | Piperacillin |
| D000667 | Ampicillin |
| D010400 | Penicillin G |
| D013457 | Sulfur Compounds |
| D013450 | Sulfones |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D013845 | Thienamycins |
| D015780 | Carbapenems |