Safety and Efficacy of Vancomycin Plus Beta-lactams (SEVPB)

• ClinicalTrials.gov Identifier: NCT03776409
• Recruitment Status: Completed
• First Posted: December 14, 2018
• Last Update Posted: June 23, 2020
• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Collaborator: Second Affiliated Hospital Xi'an Jiaotong University
• Information provided by (Responsible Party): First Affiliated Hospital Xi'an Jiaotong University

Study Description

Brief Summary:

The combination of vancomycin and piperacillin-tazobactam has been associated with an increased risk of acute kidney injury (AKI) in non-critically ill patient populations, but it is still unknown if this association exists in critically ill patients. The objective of this study is to compare AKI and efficacy of vancomycin plus piperacillin-tazobactam or beta-lactams.

Condition or disease	Intervention/treatment
Critical Illness	Drug: vancomycin plus piperacillin/tazobactam; Drug: vancomycin plus other beta-lactams

Detailed Description:

The combination of vancomycin and piperacillin-tazobactam has been associated with an increased risk of acute kidney injury (AKI) in non-critically ill patient populations, but limited data regarding this association exists in critically ill patients. The objective of this study is to compare AKI and efficacy of vancomycin plus piperacillin-tazobactam or beta-lactams.

This is a multicenter, retrospective cohort study. Patients from the retrospective cohort will be divided into 2 groups based on the combination regimen received . Patients who meet the inclusion and exclusion criteria will be included in our registry. As a non-intervention study, these information as below will be collected: basic demographics, diagnosis, concomitant nephrotoxic and other antibiotic medications, serum creatine levels, vancomycin concentrations, and indication for antibiotics.

Study Design

• Study Type: Observational
• Actual Enrollment: 700 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Comparison of the Nephrotoxicity of Vancomycin in Combination With Piperacillin/Tazobactam or Other Beta-lactams in Critically Ill Patients: A Retrospective, Multicenter Study in China
• Actual Study Start Date: December 12, 2018
• Actual Primary Completion Date: May 30, 2020
• Actual Study Completion Date: May 30, 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
vancomycin plus piperacillin/tazobactam; Critically ill patients who received the combination of VAN (vancomycin) and PTZ (piperacillin/tazobactam) for at least 48 hours during an ICU (intensive care unit) admission, had a baseline serum creatinine (Scr) concentration value within 24 hours of hospital admission.The dosage and frequency of VAN and PTZ were adjusted based on clinical practice and patient characteristics. This is an observational study without any intervention.	Drug: vancomycin plus piperacillin/tazobactam; Patients in intensive care unit who received the combination of VAN(vancomycin) and PTZ (piperacillin/tazobactam) for at least 48 hours, had a serum creatinine level measured in the 24-hour of hospital admission.The dosage and frequency of VAN and PTZ was adjusted based on clinical practice and patient characteristics.
vancomycin plus other beta-lactams; Critically ill patients who received the combination of VAN (vancomycin) and other beta-lactams (cefoperazone/sulbactam, meropenem, imipenem/siastatin, ceftriaxone, ceftazidime, et al) for at least 48 hours during an ICU (intensive care unit) admission, had a baseline serum creatinine (Scr) concentration value within 24 hours of hospital admission.The dosage and frequency of VAN and other beta-lactams were adjusted based on clinical practice and patient characteristics. This is an observational study without any intervention.	Drug: vancomycin plus other beta-lactams; Patients in intensive care unit who received the combination of VAN (vancomycin) and other beta-lactams (cefoperazone/sulbactam, meropenem, imipenem/siastatin, ceftriaxone, ceftazidime, et al) for at least 48 hours, had a baseline serum creatinine (Scr) concentration value within 24 hours of hospital admission.The dosage and frequency of VAN and other beta-lactams were adjusted based on clinical practice and patient characteristics.

Outcome Measures

Primary Outcome Measures :

1. AKI(acute kidney injury) [ Time Frame: from 24 hours after the start of the combination until discharge up to one month ]
   the incidence of acute kidney injury
2. clinical efficacy [ Time Frame: from 24 hours after the start of the combination until discharge up to one month ]
   microbial eradication

Secondary Outcome Measures :

1. the length of hospital stay [ Time Frame: from hospital admission to discharge up to one month ]
2. duration of AKI [ Time Frame: the time from AKI onset to resolution of AKI up to one month ]
3. onset of AKI [ Time Frame: the first occurence of AKI after starting concomitant antimicrobial use up to one month ]
4. whether renal function return to baseline or not [ Time Frame: from AKI onset to resolution of defined AKI up to one month ]
   whether defined AKI was resoluted or not
5. major acute kidney events at 30 days (MAKE30) [ Time Frame: MAKE30 is assessed 30 days following AKI diagnosis ]
   MAKE30 is assessed 30 days following AKI diagnosis, which is a composite outcome of death, new dialysis, and worsened renal function.
6. vancomycin trough value assessment [ Time Frame: from hospital admission to discharge up to one month ]
   assess the impact of vancomycin exposures on development of AKI

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

critically ill patients

Criteria

Inclusion Criteria:

• 18 years or older,
• admitted to intensive care unit
• received the combination of vancomycin and beta-lactams for at least 48 hours
• had a serum creatinine level measured within 24-hour hospital admission
• had at least one VAN level drawn while receiving a combination of study antibiotics

Exclusion Criteria:

• pregnancy or lactating patients
• admission to the intensive care unit during administration or within 72 hours of completing the antibiotics
• had end-stage renal disease
• died within 48 hours of combination antibiotic therapy initiation

Contacts and Locations

Locations

China, Shaanxi

First Affiliated Hospital of Xian Jiaotong University

Xi'an, Shaanxi, China, 710061

Sponsors and Collaborators

First Affiliated Hospital Xi'an Jiaotong University

Second Affiliated Hospital Xi'an Jiaotong University

Investigators

• Principal Investigator: Yalin Dong, Ph.D; First Affiliated Hospital of Xian Jiaotong University

More Information

• Responsible Party: First Affiliated Hospital Xi'an Jiaotong University
• ClinicalTrials.gov Identifier: NCT03776409
• Other Study ID Numbers: XJTU1AF2018LSK-169
• First Posted: December 14, 2018
• Last Update Posted: June 23, 2020
• Last Verified: December 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Vancomycin; Critical Illness; Disease Attributes; Pathologic Processes; Tazobactam; Piperacillin; Piperacillin, Tazobactam Drug Combination; Lactams; beta-Lactams; Anti-Bacterial Agents; Anti-Infective Agents; beta-Lactamase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action