The VPT Safety Trial (VPS) compares two common antibiotic combinations to see how they affect the kidneys of patients in the hospital with serious infections. Both combinations are approved by the Food and Drug Administration (FDA). The goal is to help doctors know which combination is safer so they can make better choices for their patients.
* What is the study's main question? Does the antibiotic combination vancomycin and piperacillin/tazobactam (VPT) cause kidney problems (acute kidney injury or AKI)? * What is the Background to the Research Question? VPT is the most common antibiotic combination used for patients in the hospital with serious infections. Some studies using a standard kidney blood test (creatinine) show more kidney problems (AKI) with VPT than with other antibiotic combinations, but these studies are not always very accurate. Because of this, some doctors use other combinations like vancomycin and cefepime (VC) or vancomycin and meropenem (VM). However, these other combinations may have their own risks, like infections that are hard to treat, serious diarrhea, higher cost, or problems with the brain. One study used a better kidney blood test (cystatin C) and did not find more kidney problems with VPT. Another more accurate type of study (randomized clinical trial) also did not find more kidney problems with VPT, but some people did not agree with how that study was done. So, doctors are still not sure if VPT causes more kidney problems, or if they should use VPT or another antibiotic combination for patients in the hospital with serious infections. * Why is AKI important? AKI is important because people who get it may have more heart and kidney problems, might need dialysis, stay in the hospital longer, have more hospital visits, higher costs, and a higher chance of death. Avoiding AKI can help prevent these problems. * How will this study help answer the question? VPS is a randomized study, which is usually more accurate, and uses a better kidney function blood test (cystatin C). The results will help doctors make better guidelines, improve care, and keep patients safer. * What are the goals of VPS? The main goal is to find out if VPT really causes kidney problems, so doctors can choose the best antibiotics for patients with serious infections. The study will look at differences in a special kidney blood test (cystatin C) between patients getting VPT and those getting VM. Other goals are to compare things like kidney problems, infections, how long patients stay in the hospital, repeat hospital visits, if patients need a breathing machine or medicine for low blood pressure, quality of life, and death rates.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
852
PT Dosing (concealed): PT dosing is standard irrespective of infection severity. 4.5 gm IV loading dose over 30 min, then 4.5 g IV over 4 hr (extended infusion) 6 hrs after the loading dose, and then q 8 hr
M dosing (concealed): M dosing depends on infection severity. 1 gm loading IV dose over 30 min, then 1 gm IV over 4 hr (extended infusion) q 8 hr (default dosing). Clinician has option to increase to 2 gm IV q 8 hr for severe infections and to decrease back to default dosing if previously chosen higher dosing is no longer deemed indicated.
Bassett Medical Center
Cooperstown, New York, United States
RECRUITINGWake Forest University Health Sciences
Winston-Salem, North Carolina, United States
RECRUITINGWest Virginia University
Morgantown, West Virginia, United States
RECRUITINGSerum cystatin C (Scys)
Difference between highest Scys (mg/L) post-treatment over 7 days minus Scys pre-treatment, expressed as ratio of pre-treatment level
Time frame: 7 days
Acute Kidney injury (AKI)/death
AKI/death KDIGO ADQI stages 0-4 (expanded with injury biomarkers) (Scr-Scys, Scys, Scr based) (transient \<72 vs. persistent \>72 hr) rate
Time frame: 7 days
Infectious complications
MDR (MRSA, VRE, ESBL, CRE)/fungal/CDI rate
Time frame: 90 days
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