Recruiting

VN & PT, VN & CP

Sponsor:

University of Pennsylvania

Code:

NCT06954129

Conditions

Acute Kidney Injury

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Vancomycin

Piperacillin-tazobactam

Cefepime

Study Details

Brief 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 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.

Conditions

Acute Kidney Injury

Study ID

NCT06954129

Start date

Jan 28, 2026

Status verified date

Feb, 2026

Completion date

Jul, 2029

Anticipated

Primary completion date

May, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

750 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

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

Interventions

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.

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

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

Primary outcome measure

  • Serum Cystatin C Concentration [ Time Frame: 5 days post enrollment ]

Central Contacts and Locations

Central contacts

Locations

University of Pennsylvania Health System

Recruiting

Philadelphia, Pennsylvania, United States, 19104

More Information

Sponsor

University of Pennsylvania

Last update posted

Feb 13, 2026

Last verified

Feb, 2026

Keywords

  • vancomycin
  • piperacillin-tazobactam
  • cefepime
  • acute kidney injury
  • nephrotoxicity
  • cystatin c
  • kidney injury molecule 1 (KIM1)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by University of Pennsylvania on 2026-02-13.