InfectionPhase 4VPSNCT07556107
The Vancomycin Piperacillin/Tazobactam (VPT) Patient Safety Trial (VPS)
A Phase 4 study testing Piperacillin + Tazobactam and meropenem in people with Infection and Acute Kidney Injury, run by Bassett Healthcare at 7 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infection, Acute Kidney Injury, Sepsis
- What is being tested?
- Piperacillin + Tazobactam and meropenem
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 852 participants
- Where
- 7 sitesUnited States
- Study dates
- 17 Aug 2026to 31 Dec 2028
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Show all 10Show fewer
- 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.
Who cannot join
None listed.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Aletha Sprague contact
7 sites in 1 country
United States7 sites, 7 recruiting
- Recruiting
Medical University of South Carolina - South Carolina Clinical & Translational Research Institute
Charleston, South Carolina, 29425
Della MacNicholas, 843-792-8385, macnichd@musc.edu
John McKinnon, MD
- Recruiting
Bassett Medical Center
Cooperstown, New York, 13326
Jennifer Victory, 6075476965, jennifer.victory@bassett.org
- Not yet recruiting
NY Presbyterian/Queens
Flushing, New York, 11355
Helen Varghese, 407-761-7115, uon9006@nyp.org
Matthew McCarthy, MD
- Recruiting
West Virginia University
Morgantown, West Virginia, 26506
Karen Hunter, (304) 293-7348, karen.hunter@hsc.wvu.edu
Daphne-Dominique Villanueva, MD
- Recruiting
University of Nebraska Medical Center
Omaha, Nebraska, 68198-1150
Brooklin Zimmerman, 402-559-5237, brooklin.zimmerman@unmc.edu
Aaron Barksdale, MD
- Recruiting
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Karen Ayala Baylon, (336) 716-5044, Karen.Ayalabaylon@Advocatehealth.org
Christine Rogers, (336) 716-3978, christine.rogers2@advocatehealth.org
- Not yet recruiting
University of Massachusetts Chan Medical School
Worcester, Massachusetts, 01655
Melissa Adams, 508-856-5012, Melissa.Adams@umassmed.edu
Jennifer Wang, MD
About this study
Official title: 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.
Read the 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.
- Conditions
- Infection, Acute Kidney Injury, Sepsis
- Being tested
- Piperacillin + Tazobactam, meropenem
- Keywords
- infection, hospitalized, AKI, cystatin c, vancomycin, piperacillin/tazobactam, meropenem, RCT
- Medical subject headings
- Infections, Acute Kidney Injury, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Piperacillin + TazobactamDrug
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
meropenemDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Piperacillin/tazobactam | Active comparator | Vancomycin plus piperacillin/tazobactam Receives: Drug: Piperacillin + Tazobactam |
| Meropenem | Active comparator | Vancomycin plus meropenem Receives: Drug: meropenem |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 7 days
Secondary outcomes (2)
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
Measured: 7 days
Infectious complications
MDR (MRSA, VRE, ESBL, CRE)/fungal/CDI rate
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2026
- Study start17 Aug 2026
- Primary completion30 Jun 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Comparative Effectiveness (safety) Research, mRCT, standard care treatment/control, parallel group, quadruple-blinded, pragmatic, adaptive (sample size reassessment), noninferiority, and individual level randomization.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 852 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bassett Healthcare
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University, Patient-Centered Outcomes Research Institute
- Responsible party
- Principal investigator, Daniel Freilich, MD, Bassett Healthcare
- Investigators
- Daniel Freilich, MD, Principal investigator, Bassett Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07556107
- Sponsor's protocol ID
- IRB00538615
- Other IDs
- BPS-2024C3-42018
- Acronym
- VPS
- Status last verified
- Oct 2026
- First submitted
- 3 Feb 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 35833959Rahman M, Shad F, Smith MC. Acute kidney injury: a guide to diagnosis and management. Am Fam Physician. 2012 Oct 1;86(7):631-9.
PubMed 23062091Mishra 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.
PubMed 15811456FDA. 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 Randomized Clinical Trial. JAMA. 2023 Oct 24;330(16):1557-1567. doi: 10.1001/jama.2023.20583.
PubMed 37837651Cote 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.
PubMed 37558318Blair 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.
PubMed 33735856Kimball 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.
PubMed 33983389Downes 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.
PubMed 29507935Goodman 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.
PubMed 32421195Chen 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.
PubMed 37040818Alosaimy 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.
PubMed 35982631Hammond 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.
PubMed 26952639Giuliano 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.
PubMed 27805728Hammond 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.
PubMed 27940946