Does Cefoxitin or Piperacillin-Tazobactam Prevent Postoperative Surgical Site Infections After Pancreatoduodenectomy?

A Phase III Multicenter, Open Label Randomized Controlled Trial of Cefoxitin Versus Piperacillin-Tazobactam as Surgical Antibiotic Prophylaxis in Patients Undergoing Pancreatoduodenectomy

The purpose of this study is to figure out which commonly used antibiotic, cefoxitin or piperacillin-tazobactam, is better at decreasing the rate of surgical site infections after pancreatoduodenectomy.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer; Pancreatic Diseases; Pancreas Cancer
• Intervention / Treatment: Drug: Cefoxitin; Drug: Piperacillin-tazobactam

• Study Type: Interventional
• Enrollment (Actual): 967
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada
      • Hamilton Health Sciences Center (Juravinski Hospital)
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medicine (Data Collection)
    • Evanston, Illinois, United States, 60201
      • NorthShore University Health System
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • St Louis, Missouri, United States, 63110
      • University of Washington School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68198-7680
      • University of Nebraska Medical Center
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge (Consent Only)
    • Hackensack, New Jersey, United States, 07601
      • Hackensack Meridian Health / Hackensack University Medical Center Cancer Center
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack (Consent Only)
    • Harrison, New York, United States, 10604
      • Memoral Sloan Kettering Westchester (Consent only)
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • New York, New York, United States, 10029
      • Mount Sinai West
    • The Bronx, New York, United States, 10467
      • Montefiore Health Systems (Montefiore Medical Center)
  • North Carolina
    • Durham, North Carolina, United States, 27713
      • Duke University
    • Greenville, North Carolina, United States, 27834
      • Brody school of Medicine at East Carolina University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Health & Services (Portland Med Ctr)
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Pennsylvania State Hershey
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Baptist Memorial Healthcare
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Scott & White Health
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Healthcare
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Foundation
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age >/= 18 years
• Patients undergoing elective pancreatoduodenectomy (PD) for any diagnosis/indication

Exclusion Criteria:

• Patients undergoing a minimally invasive PD, such as laparoscopic or robotic PD
• Patients with known and documented allergies to any of the penicillins, cephalosporins, or β-lactamase inhibitors
• Patients who are otherwise ineligible to receive the antibiotics in this study
• Patients highly unlikely to undergo PD according to the surgeon's judgment, such as conditions amenable to pancreas enucleation, ampullectomy, etc.
• Patients with long-term glucocorticosteroid use. The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular)
• Patients unable to provide informed consent
• Creatinine clearance (CrCl) </= 40 mL/min
• Patients receiving hemodialysis or peritoneal dialysis
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
• Patients with a known bacterial infection present at the time of surgery or who received antimicrobial therapy within 7 days prior to surgery

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: Cefoxitin	Drug: Cefoxitin; Participants will receive one dose of cefoxitin within 1 hour of incision time, redosed every 2-4 hours in the operating room until closure of the incision, and discontinued within 24 hours after anesthesia end time.
Experimental: Piperacillin-tazobactam	Drug: Piperacillin-tazobactam; Participants will receive one dose of piperacillin-tazobactam within 1 hour of incision time, redosed every 2-4 hours in the operating room until closure of the incision, and discontinued within 24 hours after anesthesia end time.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Evaluated for the Effectiveness of Cefoxitin as a Surgical Antibiotic Prophylaxis.	To compare the effectiveness of cefoxitin, a second generation cephalosporin (Cohort 1), with piperacillin-tazobactam, a broad-spectrum penicillin (Cohort 2), as surgical antibiotic prophylaxis in decreasing the overall rate of postoperative SSIs in patients undergoing PD. The primary endpoint, overall SSI rate, is defined as superficial incisional SSI, deep incisional SSI, or organ/space SSI within the first 30 days after the operation, as defined according to the ACS NSQIP data collection operations manual.	30 days

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Johns Hopkins University; Massachusetts General Hospital; Fox Chase Cancer Center; Washington University School of Medicine; Northwestern University; University of Chicago; University of Iowa; University of Wisconsin, Madison; The Cleveland Clinic; Emory University; Milton S. Hershey Medical Center; University of California, Davis; Ohio State University; University of Texas Southwestern Medical Center; Temple University; Rhode Island Hospital; University of Utah; Indiana University; Thomas Jefferson University; Baylor Scott and White Health; Providence Health & Services; Hackensack Meridian Health; Mount Sinai Hospital, New York; Albany Medical College; Intermountain Health Care, Inc.; Baptist Memorial Health Care Corporation; Advocate Illinois Masonic Medical Center; Gundersen Lutheran Medical Center; Hamilton Health Sciences Center; Jersey Shore Medical Center (Hackensack Meridian); Montefiore Medical Center/Albert Einstein College of Medicine; North Shore University HealthSystem; Stony Brook Medicine; Sunnybrook Health Sciences Centre, Canada; The Ottowa Hospital/University of Ottowa; Universtiy of Mississippi Medical Center; Brody School of Medicine at East Carolina University
• Investigators: Principal Investigator: Michael D'Angelica, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• Nevarez NM, Brajcich BC, Liu J, Ellis R, Ko CY, Pitt HA, D'Angelica MI, Yopp AC. Cefoxitin versus piperacillin-tazobactam as surgical antibiotic prophylaxis in patients undergoing pancreatoduodenectomy: protocol for a randomised controlled trial. BMJ Open. 2021 Mar 4;11(3):e048398. doi: 10.1136/bmjopen-2020-048398.
• D'Angelica MI, Ellis RJ, Liu JB, Brajcich BC, Gonen M, Thompson VM, Cohen ME, Seo SK, Zabor EC, Babicky ML, Bentrem DJ, Behrman SW, Bertens KA, Celinski SA, Chan CHF, Dillhoff M, Dixon MEB, Fernandez-Del Castillo C, Gholami S, House MG, Karanicolas PJ, Lavu H, Maithel SK, McAuliffe JC, Ott MJ, Reames BN, Sanford DE, Sarpel U, Scaife CL, Serrano PE, Smith T, Snyder RA, Talamonti MS, Weber SM, Yopp AC, Pitt HA, Ko CY. Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial. JAMA. 2023 May 9;329(18):1579-1588. doi: 10.1001/jama.2023.5728.

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2017
• Primary Completion (Actual): January 28, 2025
• Study Completion (Actual): January 28, 2025

Study Registration Dates

• First Submitted: August 30, 2017
• First Submitted That Met QC Criteria: August 30, 2017
• First Posted (Actual): September 1, 2017

Study Record Updates

• Last Update Posted (Estimated): October 21, 2025
• Last Update Submitted That Met QC Criteria: October 3, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: piperacillin-tazobactam; cefoxitin; pancreatoduodenectomy; 17-418
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Neoplasms; Pancreatic Diseases; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Amides; Drug Combinations; Penicillin G; beta-Lactams; Lactams; Cephalosporins; Thiazines; Sulfones; Tazobactam; Penicillanic Acid; Piperacillin; Ampicillin; Penicillins; Cephamycins; Piperacillin, Tazobactam Drug Combination; Cefoxitin
• Other Study ID Numbers: 17-418

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No