A Pragmatic Clinical Trial Comparing the Risk of Acute Kidney Injury During Treatment With Vancomycin and Piperacillin-Tazobactam vs. Vancomycin and Cefepime in Hospitalized Patients (MONACO)

February 10, 2026 updated by: Todd Miano, University of Pennsylvania

Markers of Nephrotoxicity During Treatment With Antibiotic Combinations: A Pragmatic Clinical Trial

Hospitalized patients with suspected or confirmed infection are commonly treated with vancomycin (VN) in combination with either piperacillin-tazobactam (PT) or cefepime (CP). Although these regimens have similar effectiveness, recent observational evidence suggests they may differ in terms of the risk for acute kidney injury (AKI). Interpretation of existing evidence is complicated by the limitations of creatinine, the standard biomarker used to monitor kidney function, which has poor sensitivity and specificity for drug induced AKI. To address this important knowledge gap, the investigators propose to conduct a pragmatic, open-label, non-inferiority trial that will examine the comparative risk of AKI between these standard-of-care antibiotic combinations using sensitive and specific markers of drug-induced AKI. We hypothesize that the regimen of VN in combination with PT (VN+PT) is noninferior to the regimen of VN in combination with CP (VN+CP) in terms of AKI risk.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

750

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 Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania Health System

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. Age of at least 18 years
  2. Suspected or confirmed infection based on clinical criteria, for which vancomycin with piperacillin-tazobactam or vancomycin with cefepime was prescribed by the treating clinician, as evidenced by orders being placed in the electronic health record
  3. The treating clinician considers both vancomycin with piperacillin- tazobactam or vancomycin with cefepime as acceptable treatment
  4. The treating clinician anticipates at least 48 hours of antibiotic treatment

Exclusion Criteria:

  1. Dialysis dependence or documented end stage kidney disease
  2. AKI at baseline
  3. Expected survival <24 hours and/or presence of do not resuscitate orders
  4. History of antibiotic-resistant organisms (microbiological culture results showing bacterial isolates with resistant or intermediate susceptibility to any study drug within the prior 90 days)
  5. Documented allergy to vancomycin, cephalosporins, or penicillin
  6. Suspected central nervous system infection
  7. Inability to provide informed consent or lack of proxy for consent
  8. Prisoners/incarcerated individuals
  9. Known pregnancy or breastfeeding
  10. Previous enrollment in this study
  11. Receipt of vancomycin, piperacillin-tazobactam, or cefepime for >24 hours within the preceding 7 days. At the time of screening, one-time doses of vancomycin, with or without piperacillin-tazobactam, or cefepime, will be allowed prior to randomization to avoid treatment delays; such patients must be enrolled within twelve hours of antibiotic administration.

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Vancomycin with Piperacillin-Tazobactam
Participants in the Vancomycin with Piperacillin-Tazobactam arm will be randomized to initial treatment with Vancomycin with Piperacillin-Tazobactam. Subsequent management of antimicrobial treatment will be at the discretion of treating clinicians
Drug: Vancomycin
Vancomycin is a glycopeptide antibiotic used to treat infections caused by Gram-positive bacteria, including those due to methicillin-resistant Staphylococcus aureus. Dosing of vancomycin will follow standard of care procedures, including the use of individualized dosing regimens developed in consultation with clinical pharmacists, based on participant body weight and renal function, and dosage titration guided by therapeutic drug monitoring. Vancomycin is administered via intermittent intravenous infusions of 60-90 minutes.
Drug: Piperacillin-tazobactam
Piperacillin-tazobactam is an anti-pseudomonal penicillin with a dose range of 2.25 g or 4.5 g and frequency of every 6 or 8 hours based on a participant's body weight, renal function, and clinician discretion. Piperacillin-tazobactam is administered via extended-duration (4 hours) intravenous infusions
Active Comparator: Vancomycin with Cefepime
Participants in the Vancomycin with Cefepime arm will be randomized to initial treatment with Vancomycin with Cefepime. Subsequent management of antimicrobial treatment will be at the discretion of treating clinicians
Drug: Vancomycin
Vancomycin is a glycopeptide antibiotic used to treat infections caused by Gram-positive bacteria, including those due to methicillin-resistant Staphylococcus aureus. Dosing of vancomycin will follow standard of care procedures, including the use of individualized dosing regimens developed in consultation with clinical pharmacists, based on participant body weight and renal function, and dosage titration guided by therapeutic drug monitoring. Vancomycin is administered via intermittent intravenous infusions of 60-90 minutes.
Drug: Cefepime
Cefepime is an anti-pseudomonal cephalosporin with a dose range of 500 mg, 1,000 mg, or 2,000 mg, and frequency every 8, 12, or 24 hours based on a participant's body weight, renal function, and clinician discretion. Cefepime is administered via extended-duration (4 hours) intravenous infusions

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum Cystatin C Concentration
Time Frame: 5 days post enrollment
Change in serum cystatin c concentration through Day 5 after antibiotic initiation.
5 days post enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Kidney injury molecule 1 (KIM1)
Time Frame: 5 days post enrollment
Changes in urinary KIM1 concentration through Day 5 after antibiotic initiation.
5 days post enrollment
Serum creatinine concentration
Time Frame: 5 days post enrollment
Change in serum creatinine concentration through Day 5 after antibiotic initiation.
5 days post enrollment
Acute Kidney Injury
Time Frame: At 7 and 14 days

Acute kidney injury as defined by Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria:

Stage 1 AKI (Creatinine increase by 1.5-1.9 times baseline OR increase by >= 0.3 mg/dL) Stage 2 AKI (Creatinine increase by 2.0-2.9 times baseline) Stage 3 AKI (Creatinine increase by >= 3.0 times baseline OR increase to >= 4.0 mg/dL OR New renal replacement therapy (RRT))
At 7 and 14 days
Major Adverse Kidney Events (MAKE)
Time Frame: 30 and 60 days
MAKE consists of death, need for RRT, or persistent kidney dysfunction (decrease in estimated glomerular filtration rate (GFR) to <75% of baseline)
30 and 60 days

Collaborators and Investigators

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

Sponsor

University of Pennsylvania

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

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 (Actual)

January 28, 2026

Primary Completion (Estimated)

May 1, 2029

Study Completion (Estimated)

July 1, 2029

Study Registration Dates

First Submitted

April 23, 2025

First Submitted That Met QC Criteria

April 23, 2025

First Posted (Actual)

May 1, 2025

Study Record Updates

Last Update Posted (Actual)

February 13, 2026

Last Update Submitted That Met QC Criteria

February 10, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 858301

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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