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CompletedNCT03269994Updated Oct 21, 2025Results posted

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

A Phase 3 interventional study of Cefoxitin and Piperacillin-tazobactam in Pancreatic Cancer, Pancreas Cancer and Pancreatic Diseases, sponsored by Memorial Sloan Kettering Cancer Center. Completed at 32 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-10-21.

Sponsored by Memorial Sloan Kettering Cancer Center · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
967
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • Pancreatic Cancer
  • Pancreas Cancer
  • Pancreatic Diseases

Keywords

  • pancreatoduodenectomy
  • 17-418
  • cefoxitin
  • piperacillin-tazobactam
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

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

Exclusion criteria

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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
967 participants (actual)

Study arms

  • Active comparator
    Cefoxitin

    Drug: Cefoxitin

  • Experimental
    Piperacillin-tazobactam

    Drug: Piperacillin-tazobactam

Interventions

  • DrugCefoxitin

    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.

  • DrugPiperacillin-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.

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 30 days

06

Results

Posted Oct 21, 2025

Participant flow

Participant flow — Overall Study
MilestoneCefoxitinPiperacillin-tazobactam
Started484483
Completed400378
Not completed84105
Withdrew: Withdrawal by subject45
Withdrew: Unresectable at surgery3958
Withdrew: Patient canceled surgery514
Withdrew: Preoperative progression149
Withdrew: Preoperative infection104
Withdrew: Kidney insufficiency10
Withdrew: Drug allergy02
Withdrew: Operation changed to different resection90
Withdrew: Preoperative steroid03
Withdrew: Accrual closed20
Withdrew: Operation changed to different resection010

Outcome measures

PrimaryNumber 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.

Time frame:
30 days
Reported as:
Count of participants · Participants
Number of Participants Evaluated for the Effectiveness of Cefoxitin as a Surgical Antibiotic Prophylaxis.
ParticipantsCefoxitinPiperacillin-tazobactam
Number of Participants Evaluated for the Effectiveness of Cefoxitin as a Surgical Antibiotic Prophylaxis.400378

Adverse events

Collected over 30 days. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cefoxitin10/400 (2.5%)10/400 (2.5%)0/400 (0%)
Piperacillin-tazobactam5/378 (1.3%)5/378 (1.3%)0/378 (0%)
Most frequent serious events
Most frequent serious events
EventCefoxitinPiperacillin-tazobactam
DeathGeneral disorders10/4005/378

Baseline characteristics

Age, Continuous
Age, Continuous(years)CefoxitinPiperacillin-tazobactamTotal
Median68.0 (59.8 to 73.9)66.8 (59.6 to 73.8)67.0 (59.6 to 73.9)
Sex: Female, Male
Sex: Female, Male(Participants)CefoxitinPiperacillin-tazobactamTotal
Female177145322
Male223233456
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)CefoxitinPiperacillin-tazobactamTotal
Hispanic or Latino6612
Not Hispanic or Latino307280587
Unknown or Not Reported8792179
Race (NIH/OMB)
Race (NIH/OMB)(Participants)CefoxitinPiperacillin-tazobactamTotal
American Indian or Alaska Native011
Asian4812
Native Hawaiian or Other Pacific Islander000
Black or African American271946
White276258534
More than one race000
Unknown or Not Reported9392185
Region of Enrollment
Region of Enrollment(Participants)CefoxitinPiperacillin-tazobactamTotal
United States400378778
07

Study locations

32 sites
  • UC Davis Comprehensive Cancer Center
    Sacramento, California 95817, United States
  • Emory University School of Medicine
    Atlanta, Georgia 30322, United States
  • Northwestern Medicine (Data Collection)
    Chicago, Illinois 60611, United States
  • NorthShore University Health System
    Evanston, Illinois 60201, United States
  • Indiana University
    Indianapolis, Indiana 46202, United States
  • University of Iowa
    Iowa City, Iowa 52242, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • University of Washington School of Medicine
    St Louis, Missouri 63110, United States
  • University of Nebraska Medical Center
    Omaha, Nebraska 68198-7680, United States
  • Memorial Sloan Kettering Basking Ridge (Consent only)
    Basking Ridge, New Jersey 07920, United States
  • Hackensack Meridian Health / Hackensack University Medical Center Cancer Center
    Hackensack, New Jersey 07601, United States
  • Memorial Sloan Kettering Commack (Consent only)
    Commack, New York 11725, United States
  • Memoral Sloan Kettering Westchester (Consent only)
    Harrison, New York 10604, United States
  • Mount Sinai Hospital
    New York, New York 10029, United States
  • Mount Sinai West
    New York, New York 10029, United States
  • Memorial Sloan Kettering Cancer Center
    New York, New York 10065, United States
  • Montefiore Health Systems (Montefiore Medical Center)
    The Bronx, New York 10467, United States
  • Duke University
    Durham, North Carolina 27713, United States
  • Brody School of Medicine at East Carolina University
    Greenville, North Carolina 27834, United States
  • Ohio State University
    Columbus, Ohio 43210, United States
  • Providence Health & Services (Portland Med Ctr)
    Portland, Oregon 97213, United States
  • Pennsylvania State Hershey
    Hershey, Pennsylvania 17033, United States
  • Thomas Jefferson University Hospital
    Philadelphia, Pennsylvania 19107, United States
  • Baptist Memorial Healthcare
    Memphis, Tennessee 38120, United States
  • Baylor Scott & White Health
    Dallas, Texas 75246, United States
  • Intermountain Healthcare
    Murray, Utah 84107, United States
  • University of Utah
    Salt Lake City, Utah 84112, United States
  • Gundersen Lutheran Medical Foundation
    La Crosse, Wisconsin 54601, United States
  • University of Wisconsin
    Madison, Wisconsin 53792, United States
  • Hamilton Health Sciences Center (Juravinski Hospital)
    Hamilton, Ontario, Canada
  • Ottawa Hospital
    Ottawa, Ontario K1H 8L6, Canada
  • Sunnybrook Health Sciences Centre
    Toronto, Ontario M4N 3M5, Canada
08

References and documents

Publications

  • 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. PubMed 37078771 ↗
  • 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. PubMed 33664081 ↗

Study documents

  • Protocol and statistical analysis plan · Dec 20, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

09

Registry details

Key details

Study ID
NCT03269994
Lead sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Indiana University, Massachusetts General Hospital, Thomas Jefferson University, Washington University School of Medicine, Advocate Illinois Masonic Medical Center, Baptist Memorial Health Care Corporation, Baylor Scott and White Health, The Cleveland Clinic, Emory University, Fox Chase Cancer Center, Gundersen Lutheran Medical Center, Hackensack Meridian Health, Hamilton Health Sciences Center, Intermountain Health Care, Inc., Jersey Shore Medical Center (Hackensack Meridian), Johns Hopkins University, Montefiore Medical Center/Albert Einstein College of Medicine, North Shore University HealthSystem, Milton S. Hershey Medical Center, Rhode Island Hospital, Stony Brook Medicine, Sunnybrook Health Sciences Centre, Temple University, Ohio State University, The Ottowa Hospital/University of Ottowa, University of California, Davis, University of Chicago, University of Iowa, University of Texas Southwestern Medical Center, University of Utah, University of Wisconsin, Madison, Providence Health & Services, Albany Medical College, Northwestern University, Universtiy of Mississippi Medical Center, Mount Sinai Hospital, New York, Brody School of Medicine at East Carolina University
Responsible party
Sponsor
First posted
Sep 1, 2017
Start date
Nov 21, 2017
Primary completion
Jan 28, 2025
Completion
Jan 28, 2025
Results posted
Oct 21, 2025
Last update
Oct 21, 2025

Study contacts

Michael D'Angelica, MD
principal investigator · Memorial Sloan Kettering Cancer Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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