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

NCT07556107 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: IRB00538615BPS-2024C3-42018
• Study Type: interventional
• Target: 852
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Infection; Acute Kidney Injury; Sepsis

Keywords

infection; hospitalized; AKI; cystatin c; vancomycin; piperacillin/tazobactam; meropenem; RCT

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Acute Kidney injury (AKI)/death

  7 days

• Infectious complications

  90 days

Other Outcomes (2)

• serum creatinine (Scr)

  7 days

• Kidney Injury biomarkers

  90 days

Study Arms (2)

Piperacillin/tazobactam

ACTIVE COMPARATOR

Vancomycin plus piperacillin/tazobactam

Drug: Piperacillin + Tazobactam

Meropenem

ACTIVE COMPARATOR

Vancomycin plus meropenem

Drug: meropenem

Interventions

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

Piperacillin/tazobactam

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.

Meropenem

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• \. AKI (\>/=moderate) (KDIGO stage 2-3) (Scr increase \>/=2-fold from chronic BL) (Scr based).
• \. CKD (\>/=moderately to severely decreased eGFR) (KDIGO stage G3b-G5) (by history or eGFR \</=44 mL/min/1.73M2) (Scr based).
• \. 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.

Sponsors & Collaborators

• Bassett Healthcare: lead
• Johns Hopkins University: collaborator
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (3)

Bassett Medical Center

Cooperstown, New York, 13326, United States

RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

RECRUITING

West Virginia University

Morgantown, West Virginia, 26506, United States

RECRUITING

Related Publications (18)

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  PMID: 35833959 BACKGROUND

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  PMID: 23062091 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.

  PMID: 15811456 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

  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.

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• 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.

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• 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.

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• 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 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.

  PMID: 29507935 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.

  PMID: 32421195 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.

  PMID: 37040818 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.

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• 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.

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• 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.

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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 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.

  PMID: 25291579 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.

  PMID: 29020249 BACKGROUND

MeSH Terms

Conditions

Infections; Acute Kidney Injury; Sepsis

Interventions

Piperacillin, Tazobactam Drug Combination; Meropenem

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tazobactam; Penicillanic Acid; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Piperacillin; Ampicillin; Penicillin G; Sulfur Compounds; Sulfones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Thienamycins; Carbapenems

Study Officials

• Daniel Freilich, MD

  Bassett Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Victory, RN, CCRC

CONTACT

607-547-6965; jennifer.victory@bassett.org

Aletha Sprague

CONTACT

aletha.sprague@bassett.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Attending Physician, Principal Investigator #1

Model Details: Comparative Effectiveness (safety) Research, mRCT, standard care treatment/control, parallel group, quadruple-blinded, pragmatic, adaptive (sample size reassessment), noninferiority, and individual level randomization.

Study Record Dates

• First Submitted: February 3, 2026
• First Posted: April 29, 2026
• Study Start: August 17, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: August 18, 2026

Record last verified: 2026-08

Locations

US (3)