NCT07556107

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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
852

participants targeted

Target at P75+ for phase_4

Timeline
31mo left

Started Jun 2026

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 3, 2026

Completed
3 months until next milestone

First Posted

Study publicly available on registry

April 29, 2026

Completed
1 month until next milestone

Study Start

First participant enrolled

June 1, 2026

Expected
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2028

6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2028

Last Updated

April 29, 2026

Status Verified

April 1, 2026

Enrollment Period

2.1 years

First QC Date

February 3, 2026

Last Update Submit

April 22, 2026

Conditions

InfectionAcute Kidney InjurySepsis

Keywords

infectionhospitalizedAKIcystatin cvancomycinpiperacillin/tazobactammeropenemRCT

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 + 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

Piperacillin/tazobactam
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.

Meropenem

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Bassett Medical Center

Cooperstown, New York, 13326, United States

Location

Related Publications (18)

  • 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.

    BACKGROUND

  • Rahman M, et al. Acute kidney injury: a guide to diagnosis and management. Am Fam Physician. 2012;86(7):631-639.

    BACKGROUND

  • 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.

    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, et al. Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Randomized Clinical Trial. JAMA. 2023;330(16):1557-1567.

    BACKGROUND

  • Côté JM, et al. Does Vancomycin-Piperacillin-Tazobactam Cause Pseudo-AKI, True Nephrotoxicity, or Both? Chest. 2023;164(2):273-274.

    BACKGROUND

  • Blair M, et al. Nephrotoxicity from Vancomycin Combined with Piperacillin-Tazobactam: A Comprehensive Review. Am J Nephrol. 2021;52(2):85-97.

    BACKGROUND

  • 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.

    BACKGROUND

  • Downes KJ, et al. The Cost of Vancomycin and Piperacillin/Tazobactam Treatment-Reply. JAMA Pediatr. 2018;172(5):494-495.

    BACKGROUND

  • 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.

    BACKGROUND

  • 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.

    BACKGROUND

  • 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.

    BACKGROUND

  • 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.

    BACKGROUND

  • 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.

    BACKGROUND

  • 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.

    BACKGROUND

  • 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.

    BACKGROUND

  • Magill SS, et al. Prevalence of antimicrobial use in US acute care hospitals, May-September 2011. JAMA. 2014;312(14):1438-1446.

    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;65(12):2137-2143.

    BACKGROUND

MeSH Terms

Conditions

InfectionsAcute Kidney InjurySepsis

Interventions

Piperacillin, Tazobactam Drug CombinationMeropenem

Condition Hierarchy (Ancestors)

Renal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

TazobactamPenicillanic AcidPenicillinsbeta-LactamsLactamsAmidesOrganic ChemicalsPiperacillinAmpicillinPenicillin GSulfur CompoundsSulfonesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsDrug CombinationsPharmaceutical PreparationsThienamycinsCarbapenems

Study Officials

  • Daniel Freilich, MD

    Bassett Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Amanda Hasuly

CONTACT

443-473-0986amanda.hasuly@bassett.org

Jennifer Victory

CONTACT

607-547-6965jennifer.victory@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
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.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Senior Attending Physician, Principal Investigator #1

Study Record Dates

First Submitted

February 3, 2026

First Posted

April 29, 2026

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

December 31, 2028

Last Updated

April 29, 2026

Record last verified: 2026-04

Locations

US(1)