Comparing kidney risk of vancomycin with piperacillin-tazobactam versus vancomycin with cefepime in hospitalized adults
Markers of Nephrotoxicity During Treatment With Antibiotic Combinations: A Pragmatic Clinical Trial
This study will test whether combining vancomycin with piperacillin-tazobactam causes about the same risk of acute kidney injury as combining vancomycin with cefepime in hospitalized adults with suspected or confirmed infection.
Quick facts
| Phase | Phase 4 |
|---|---|
| Study type | Interventional |
| Enrollment | 750 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of Pennsylvania Academic / other |
| Locations | 1 site (Philadelphia, Pennsylvania) |
| Trial ID | NCT06954129 on ClinicalTrials.gov |
What this trial studies
This is a pragmatic, open-label, non-inferiority trial conducted in hospitalized adults who are started on vancomycin plus either piperacillin-tazobactam or cefepime as part of routine care. The trial compares the two standard antibiotic combinations for their risk of causing acute kidney injury using more sensitive and specific biomarkers of drug-induced kidney injury rather than relying only on creatinine. Eligible patients are adults for whom the treating clinician considers either combination acceptable and who are expected to receive at least 48 hours of therapy; patients with baseline AKI, dialysis dependence, recent resistant organisms, or relevant allergies are excluded. The design aims to produce real-world evidence that can directly inform antibiotic choice in hospitals.
Who should consider this trial
Good fit: Hospitalized adults (age ≥18) with suspected or confirmed infection for whom the treating clinician considers either vancomycin+piperacillin-tazobactam or vancomycin+cefepime acceptable and who are expected to receive at least 48 hours of therapy.
Not a fit: Patients who are dialysis-dependent, have baseline acute kidney injury, have documented allergies to the study drugs, have recent antibiotic-resistant organisms, have suspected CNS infection, or are expected to die within 24 hours are excluded and would not receive benefit from participation.
Why it matters
Potential benefit: If successful, this could clarify which common antibiotic combination is safer for the kidneys and help clinicians choose regimens that reduce risk of acute kidney injury.
How similar studies have performed: Observational studies have suggested higher AKI risk with vancomycin plus piperacillin-tazobactam versus vancomycin plus cefepime, but randomized, biomarker-driven comparisons are limited and this approach is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Philadelphia, Pennsylvania
- University of Pennsylvania Health System — Philadelphia, Pennsylvania, United States (Recruiting)
Study contacts
- Study coordinator: Todd Miano, PharmD, PhD
- Email: todd.miano@pennmedicine.upenn.edu
- Phone: 215-573-5568
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.