The Vancomycin Piperacillin/Tazobactam (VPT) Patient Safety Trial (VPS)

Purpose

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.

Conditions

  • Infection
  • Acute Kidney Injury
  • Sepsis

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Hospitalized or being hospitalized. 2. Age >/=18 yr old. 3. Serious or suspected serious infection for which VPT or VM considered a broad-spectrum combination antibiotic backbone standard of care by clinician. 4. Enrollment can be completed before the first dose of abx (ideally) and no later than before the second dose (alternatively). 5. Consenting/enrollment will not clinically significantly delay abx administration. 6. Baseline and >/=1 prior Scr available (within 1 yr). 7. Pt or LAR able to provide IC.

Exclusion Criteria

  1. AKI (>/=moderate) (KDIGO stage 2-3) (Scr increase >/=2-fold from chronic BL) (Scr based). 2. CKD (>/=moderately to severely decreased eGFR) (KDIGO stage G3b-G5) (by history or eGFR </=44 mL/min/1.73M2) (Scr based). 3. Beta lactam allergy. 4. Contraindication to VPT or VM. 5. Infection requiring VPT or VM specifically or another abx regimen. 6. Participation in another research study with interventions that may impact study endpoints.

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Comparative Effectiveness (safety) Research, mRCT, standard care treatment/control, parallel group, quadruple-blinded, pragmatic, adaptive (sample size reassessment), noninferiority, and individual level randomization.
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Piperacillin/tazobactam
Vancomycin plus piperacillin/tazobactam
  • Drug: Piperacillin + Tazobactam
    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
Active Comparator
Meropenem
Vancomycin plus meropenem
  • Drug: meropenem
    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.

Recruiting Locations

Bassett Medical Center
Cooperstown, New York 13326
Contact:
Jennifer Victory
6075476965
jennifer.victory@bassett.org

Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157
Contact:
Karen Ayala Baylon
(336) 716-5044
Karen.Ayalabaylon@Advocatehealth.org

West Virginia University
Morgantown, West Virginia 26506
Contact:
Karen Hunter
(304) 293-7348
karen.hunter@hsc.wvu.edu

More Details

Status
Recruiting
Sponsor
Bassett Healthcare

Study Contact

Jennifer Victory, RN, CCRC
607-547-6965
jennifer.victory@bassett.org

Detailed Description

- 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.