Skip to main content
OpenTrials
Recruiting

NCT Number: NCT06954129

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Acute Kidney Injury Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Male Urogenital Diseases Renal Insufficiency Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location status: Recruiting

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age of at least 18 years
  • 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
  • The treating clinician considers both vancomycin with piperacillin- tazobactam or vancomycin with cefepime as acceptable treatment
  • The treating clinician anticipates at least 48 hours of antibiotic treatment

Exclusion criteria

  • Dialysis dependence or documented end stage kidney disease
  • AKI at baseline
  • Expected survival <24 hours and/or presence of do not resuscitate orders
  • 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)
  • Documented allergy to vancomycin, cephalosporins, or penicillin
  • Suspected central nervous system infection
  • Inability to provide informed consent or lack of proxy for consent
  • Prisoners/incarcerated individuals
  • Known pregnancy or breastfeeding
  • Previous enrollment in this study
  • 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.

Treatment and study plan

Vancomycin

Drug

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.

Piperacillin-tazobactam

Drug

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

Cefepime

Drug

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

Primary outcomes

  1. Serum Cystatin C Concentration

    Time frame: 5 days post enrollment

    Change in serum cystatin c concentration through Day 5 after antibiotic initiation.

Secondary outcomes

  1. Kidney injury molecule 1 (KIM1)

    Time frame: 5 days post enrollment

    Changes in urinary KIM1 concentration through Day 5 after antibiotic initiation.

  2. Serum creatinine concentration

    Time frame: 5 days post enrollment

    Change in serum creatinine concentration through Day 5 after antibiotic initiation.

  3. 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))

  4. 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)

Study contacts

Contact information is provided by the study sponsor or research team.

Todd Miano, PharmD, PhD

CONTACT

[email protected]

215-573-5568

Sponsors and collaborators

Lead sponsor

University of Pennsylvania

Other

Registry information

Official study title

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

Acronym: MONACO

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
May 1, 2025
Registry last updated
Feb 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.