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Acute Kidney InjuryPhase 4MONACONCT06954129

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

A Phase 4 study testing Vancomycin, Piperacillin-tazobactam and Cefepime in people with Acute Kidney Injury, run by University of Pennsylvania at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Kidney Injury
What is being tested?
Vancomycin, Piperacillin-tazobactam and Cefepime
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
750 participants
Where
1 siteUnited States
Study dates
28 Jan 2026to Jul 2029
Phase
Phase 4
Are there results?
Not yet: the study is under way

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

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Todd Miano, PharmD, PhD contact

215-573-5568

todd.miano@pennmedicine.upenn.edu

United States1 site, 1 recruiting
  • University of Pennsylvania Health System

    Philadelphia, Pennsylvania, 19104

    Recruiting

Other trials in United States

About this study

Official title: 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.

Being tested
Vancomycin, Piperacillin-tazobactam, Cefepime
Keywords
vancomycin, piperacillin-tazobactam, cefepime, acute kidney injury, nephrotoxicity, cystatin c, kidney injury molecule 1 (KIM1)
Medical subject headings
Acute Kidney Injury

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VancomycinDrug

    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-tazobactamDrug

    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

  • CefepimeDrug

    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

Study groups in NCT06954129
Study groupRoleWhat they receive
Vancomycin with Piperacillin-TazobactamActive comparatorParticipants 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
Receives: Drug: Vancomycin; Drug: Piperacillin-tazobactam
Vancomycin with CefepimeActive comparatorParticipants 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
Receives: Drug: Vancomycin; Drug: Cefepime

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Serum Cystatin C Concentration

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

    Measured: 5 days post enrollment

Secondary outcomes (4)
  1. Kidney injury molecule 1 (KIM1)

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

    Measured: 5 days post enrollment

  2. Serum creatinine concentration

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

    Measured: 5 days post enrollment

  3. Acute Kidney Injury

    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))

    Measured: At 7 and 14 days

  4. Major Adverse Kidney Events (MAKE)

    MAKE consists of death, need for RRT, or persistent kidney dysfunction (decrease in estimated glomerular filtration rate (GFR) to <75% of baseline)

    Measured: 30 and 60 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 May 2025
  2. Study start28 Jan 2026
  3. Primary completionMay 2029 (estimated)
  4. Study completionJul 2029 (estimated)

Resources

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
Masking
None (open label)
Enrolment
750 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06954129
Sponsor's protocol ID
858301
Acronym
MONACO
Status last verified
Feb 2026
First submitted
23 Apr 2025
Last updated
13 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Vaidya VS, Ozer JS, Dieterle F, Collings FB, Ramirez V, Troth S, Muniappa N, Thudium D, Gerhold D, Holder DJ, Bobadilla NA, Marrer E, Perentes E, Cordier A, Vonderscher J, Maurer G, Goering PL, Sistare FD, Bonventre JV. Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol. 2010 May;28(5):478-85. doi: 10.1038/nbt.1623.

    PubMed 20458318
  • Herget-Rosenthal S, Marggraf G, Husing J, Goring F, Pietruck F, Janssen O, Philipp T, Kribben A. Early detection of acute renal failure by serum cystatin C. Kidney Int. 2004 Sep;66(3):1115-22. doi: 10.1111/j.1523-1755.2004.00861.x.

    PubMed 15327406
  • Nejat M, Pickering JW, Walker RJ, Endre ZH. Rapid detection of acute kidney injury by plasma cystatin C in the intensive care unit. Nephrol Dial Transplant. 2010 Oct;25(10):3283-9. doi: 10.1093/ndt/gfq176. Epub 2010 Mar 28.

    PubMed 20350927
  • Bellos I, Karageorgiou V, Pergialiotis V, Perrea DN. Acute kidney injury following the concurrent administration of antipseudomonal beta-lactams and vancomycin: a network meta-analysis. Clin Microbiol Infect. 2020 Jun;26(6):696-705. doi: 10.1016/j.cmi.2020.03.019. Epub 2020 Mar 25.

    PubMed 32222460
  • Pais GM, Liu J, Avedissian SN, Hiner D, Xanthos T, Chalkias A, d'Aloja E, Locci E, Gilchrist A, Prozialeck WC, Rhodes NJ, Lodise TP, Fitzgerald JC, Downes KJ, Zuppa AF, Scheetz MH. Lack of synergistic nephrotoxicity between vancomycin and piperacillin/tazobactam in a rat model and a confirmatory cellular model. J Antimicrob Chemother. 2020 May 1;75(5):1228-1236. doi: 10.1093/jac/dkz563.

    PubMed 32011685
  • Avedissian SN, Pais GM, Liu J, Rhodes NJ, Scheetz MH. Piperacillin-Tazobactam Added to Vancomycin Increases Risk for Acute Kidney Injury: Fact or Fiction? Clin Infect Dis. 2020 Jul 11;71(2):426-432. doi: 10.1093/cid/ciz1189.

    PubMed 31833540
  • 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 37837651
  • 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 35833959
  • Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.

    PubMed 28101605
  • Cecconi M, Evans L, Levy M, Rhodes A. Sepsis and septic shock. Lancet. 2018 Jul 7;392(10141):75-87. doi: 10.1016/S0140-6736(18)30696-2. Epub 2018 Jun 21.

    PubMed 29937192

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Vancomycin, Piperacillin-tazobactam and Cefepime in people with Acute Kidney Injury, run by University of Pennsylvania at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 13 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Todd Miano, PharmD, PhD (215-573-5568, todd.miano@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Serum Cystatin C Concentration (time frame: 5 days post enrollment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06954129, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2026.

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