Surgical Site Infections After Liver Transplantation Based on Perioperative Antibiotics

A Randomized, Prospective Study of Surgical Site Infections in Liver Transplant Patients Receiving Three Days of Peri-operative Antibiotic Prophylaxis Versus Intra-operative Antibiotics Only

This study will be to prospectively determine differences in Surgical Site Infection (SSI) if a prolonged course of post-operative antibiotics are used following liver transplantation.

Study Overview

• Status: Completed
• Conditions: Liver Transplantation; Surgical Site Infection
• Intervention / Treatment: Drug: standard; Other: liver transplant; Drug: extended

Detailed Description

This study will be to prospectively determine differences in SSI if a prolonged course of post-operative antibiotics are used following liver transplantation. All adult patients, admitted to the University of Virginia (UVA) Medical Center for first-time liver transplantation will be randomized to the standard of care of peri-operative antibiotics or extended course of three total days.

Patients will be evaluated primarily for the presence of post-operative surgical site infections but also for fever, elevated white blood counts, secondary infections (urinary tract, pneumonia, and blood stream), length of hospital stay, graft loss, and mortality for 30 days after liver transplant.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients ≥ 18 years of age.
• Eligible for liver transplantation by UVA standard protocol.
• First-time transplantation.
• No active infections - requiring antibiotics - excluding antifungals.

Exclusion Criteria:

• All patients < 18 years of age.
• Previous liver transplantation.
• Active infections - requiring antibiotics.
• Allergy to all standard peri-operative antibiotics (piperacillin/tazobactam or UVA standard alternatives for Penicillin allergic patients: ciprofloxacin and vancomycin).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: standard peri-operative antibiotics; The standard of care at the University of Virginia Medical Center for liver transplantation patients is a 3.375 gram dose of piperacillin / tazobactam (Zosyn®) at the time of induction of anesthesia, though this dose may be adjusted for renal insufficiency. This dose is repeated during the operation every six hours.	Drug: standard; peri-operative antibiotic regimen only; Other Names: Peri-operative only antibiotics; Other: liver transplant; orthotopic liver transplantation
Experimental: extended three-day course of antibiotics; For those patients randomized to the study group, antibiotics will be started as per the usual intra-operative dosing regimen, then continued to provide coverage for 72 hours. This is typically provided as additional doses of 3.375 grams of piperacillin / tazobactam (Zosyn®) every 8 hours for 3 total days (giving a total of 72 hours of antibiotic coverage), though this may be altered based on kidney function.	Other: liver transplant; orthotopic liver transplantation; Drug: extended; extended three-day course of antibiotics; Other Names: Extended, three-day antibiotics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Development of Surgical Site Infections	development of surgical site infection, including superficial and deep incisional and organ space surgical site infections	within 30 days from surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Post-operative Fever	fever above 38.5 degrees Celsius 24 hours after the end of the liver transplant	24 hours from surgery
Number of Subjects With Elevated White Blood Count (WBC)	above 15,000 within 24hours after the end of the liver transplant	24 hours from surgery
Number of Subjects With Nosocomial Infection	diagnosis of any new infection other than an SSI within 30 days from surgery	within 30 days from surgery
Length of Hospital Stay	days hospitalized after liver transplant	within 30 days from surgery
Number of Subjects With Graft Loss	complete loss of liver function in recipient	within 30 days from surgery
Number of Subjects With Mortality	death within 30 days of liver transplant	within 30 days from surgery

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Robert G Sawyer, MD, UVA

Publications and helpful links

General Publications

• Chan S, Ng S, Chan HP, Pascoe EM, Playford EG, Wong G, Chapman JR, Lim WH, Francis RS, Isbel NM, Campbell SB, Hawley CM, Johnson DW. Perioperative antibiotics for preventing post-surgical site infections in solid organ transplant recipients. Cochrane Database Syst Rev. 2020 Aug 4;8(8):CD013209. doi: 10.1002/14651858.CD013209.pub2.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: March 2, 2016
• First Submitted That Met QC Criteria: March 22, 2016
• First Posted (Estimate): March 23, 2016

Study Record Updates

• Last Update Posted (Actual): July 17, 2018
• Last Update Submitted That Met QC Criteria: June 18, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Disease Attributes; Wound Infection; Infections; Communicable Diseases; Surgical Wound Infection; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: IRB-HSR#14971; T32AI078875 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided