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

April 22, 2026 updated by: Daniel Freilich, MD, Bassett Healthcare

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

  • 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.

Study Type

Interventional

Enrollment (Estimated)

852

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria

  1. Hospitalized or being hospitalized.
  2. Age >/=18 yr old.
  3. Serious or suspected serious infection for which VPT or VM considered a broad-spectrum combination antibiotic backbone standard of care by clinician.
  4. Enrollment can be completed before the first dose of abx (ideally) and no later than before the second dose (alternatively).
  5. Consenting/enrollment will not clinically significantly delay abx administration.
  6. Baseline and >/=1 prior Scr available (within 1 yr).
  7. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Piperacillin/tazobactam
Vancomycin plus piperacillin/tazobactam
Drug: 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
Active Comparator: Meropenem
Vancomycin plus meropenem
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum cystatin C (Scys)
Time Frame: 7 days
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute Kidney injury (AKI)/death
Time Frame: 7 days
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
Time Frame: 90 days
MDR (MRSA, VRE, ESBL, CRE)/fungal/CDI rate
90 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
serum creatinine (Scr)
Time Frame: 7 days
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
Time Frame: 90 days
NGAL, TIMP-2×IGFBP7, KIM-1, ACR
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bassett Healthcare

Collaborators

Patient-Centered Outcomes Research Institute
Johns Hopkins University

Investigators

  • Principal Investigator: Daniel Freilich, MD, Bassett Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • Miano TA, et al. 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;48(9):1144-1155.
  • Rahman M, et al. Acute kidney injury: a guide to diagnosis and management. Am Fam Physician. 2012;86(7):631-639.
  • Mishra J, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005;365(9466):1231-1238.
  • 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, et al. Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Randomized Clinical Trial. JAMA. 2023;330(16):1557-1567.
  • Côté JM, et al. Does Vancomycin-Piperacillin-Tazobactam Cause Pseudo-AKI, True Nephrotoxicity, or Both? Chest. 2023;164(2):273-274.
  • Blair M, et al. Nephrotoxicity from Vancomycin Combined with Piperacillin-Tazobactam: A Comprehensive Review. Am J Nephrol. 2021;52(2):85-97.
  • Kimball JM, et al. 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 Stewardshi. Clin Infect Dis. 2021;73(8):1397-1403.
  • Downes KJ, et al. The Cost of Vancomycin and Piperacillin/Tazobactam Treatment-Reply. JAMA Pediatr. 2018;172(5):494-495.
  • Goodman KE, et al. Significant Regional Differences in Antibiotic Use Across 576 US Hospitals and 11,701,326 Adult Admissions, 2016-2017. Clinical Infectious Diseases. 2021;73(2):213-222.
  • Chen AY, et al. A Large-Scale Multicenter Retrospective Study on Nephrotoxicity Associated With Empiric Broad-Spectrum Antibiotics in Critically Ill Patients. Chest. 2023;164(2):355-368.
  • Alosaimy S, et al. Nephrotoxicity of Vancomycin in Combination With Beta-Lactam Agents: Ceftolozane-Tazobactam vs Piperacillin-Tazobactam. Clin Infect Dis. 2023;76(3):e1444--e1455.
  • Hammond DA, et al. Comparative Incidence of Acute Kidney Injury in Critically Ill Patients Receiving Vancomycin with Concomitant Piperacillin-Tazobactam or Cefepime: A Retrospective Cohort Study. Pharmacotherapy. 2016;36(5):463-471.
  • Giuliano CA, et al. Is the Combination of Piperacillin-Tazobactam and Vancomycin Associated with Development of Acute Kidney Injury? A Meta-analysis. Pharmacotherapy. 2016;36(12):1217-1228.
  • Hammond DA, et al. Systematic Review and Meta-Analysis of Acute Kidney Injury Associated with Concomitant Vancomycin and Piperacillin/tazobactam. Clin Infect Dis. 2017;64(5):666-674.
  • Bellos I, et al. Acute kidney injury following the concurrent administration of antipseudomonal β-lactams and vancomycin: a network meta-analysis. Clin Microbiol Infect. 2020;26(6):696-705.
  • Magill SS, et al. Prevalence of antimicrobial use in US acute care hospitals, May-September 2011. JAMA. 2014;312(14):1438-1446.
  • 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;65(12):2137-2143.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

February 3, 2026

First Submitted That Met QC Criteria

April 22, 2026

First Posted (Actual)

April 29, 2026

Study Record Updates

Last Update Posted (Actual)

April 29, 2026

Last Update Submitted That Met QC Criteria

April 22, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00538615
  • BPS-2024C3-42018 (Other Grant/Funding Number: PCORI)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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