Surgical Site Infection and Antibiotic Use Study (ASSERT)

Antibiotics and Surgical Site Infection in Expander Based Breast Reconstruction Trial (ASSERT) A Multi-institutional Randomized Controlled Trial to Determine the Optimal Antibiotic Prophylaxis for Tissue Expander-based Breast Reconstruction

This study is a prospective, multi-institutional, noninferiority, randomized control trial that will compare the efficacy of two antibiotic treatments in preventing SSI in patients receiving immediate breast reconstruction with tissue expanders (TE-BR). The patients will be randomly assigned to one of the two treatment groups. One group will receive a single dose of antibiotics just before surgery and if necessary, more doses during the surgery. The other group will receive the same treatment as the first group, along with an additional week of antibiotics after surgery. The study will assess the rates of SSI from the two groups. It will also assess the type, duration and method (oral vs. intravenous) of subsequent antibiotic use for patients who develop SSIs in each group.

Study Overview

• Status: Completed
• Conditions: Surgical Site Infection; Breast Reconstruction; Antibiotic Use
• Intervention / Treatment: Drug: Single pre-operative dose of intravenous antibiotics with intraoperative redosing; Drug: One week of post-operative antibiotics

Detailed Description

Among plastic surgeons, the clinical practice of prescribing postoperative prophylactic antibiotics following postmastectomy breast reconstruction with tissue expanders ranges widely from no postoperative antibiotics, to 5-7 days post-op, to antibiotics until the drains are removed. The Centers for Disease Control and Prevention (CDC) recommends a single preoperative antibiotic dose for clean and clean-contaminated procedures, even in the presence of a drain. With the CDC creating a national action plan to reduce unnecessary prophylactic antibiotics for clean non-contaminated cases by advocating use of only a single pre-operative dose of antibiotics (see: https://www.cdc.gov/drugresistance/pdf/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf ) there is mounting pressure on the plastic surgery community to adopt this regimen of SSI prophylaxis. Because there are no definitive studies that provide sufficient or conclusive evidence to affect antibiotic practice patterns among plastic surgeons on a large-scale, plastic surgeons use a wide variety of protocols for their SSI prophylaxis, especially in implant-based breast reconstruction. Plastic surgeons have generally not adopted CDC guidelines because these recommendations were not based on studies in plastic surgery patients, and the use of foreign body implants underneath devitalized soft tissue can be associated with higher infection risks. Based on the literature and from self-reporting from ASPS membership, there is a wide range of prophylactic antibiotic use to prevent SSI from as little as one preoperative dose to many weeks of therapy; one week of post-operative antibiotics is the most common form. However, the Centers for Disease Control (CDC) recommends a single preoperative dose of antibiotics for clean cases, even in the presence of a drain. Prolonged antibiotic courses can lead to antibiotic complications and development of resistance.

Definitive studies to determine an optimal therapeutic strategy to prevent SSI in implant-based plastic surgical procedures are lacking. This study will address a dilemma in common plastic surgical operation: the use of post-operative antibiotics in prosthesis-based breast reconstruction.

The central hypothesis for this multi-institutional, prospective randomized control trial (RCT) is that a single pre-operative dose of intravenous antibiotics with intraoperative redosing (SPD) is no worse (noninferiority design) at preventing SSI in tissue expander-based breast reconstruction (TE-BR) than an additional week of post-operative antibiotic prophylaxis (WPO).

This trial will evaluate the efficacy of single preoperative dose versus one-week antibiotic regimens in preventing surgical site infection after tissue expander breast reconstruction. The investigators will assess the rates of SSI from the SPD vs. the WPO groups. They will assess the type, duration and method (oral vs. intravenous) of subsequent antibiotic use for patients who develop SSIs in each group. The study will also compare the readmission and premature expander removal rates due to SSI and the adverse antibiotic side effects in the two groups.

• Study Type: Interventional
• Enrollment (Actual): 235
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Women 18 years or older, undergoing unilateral or bilateral mastectomy (including breast cancer, any stage, or prophylactic) and immediate tissue expander reconstruction (including submuscular, submuscular and ADM, or pre-pectoral placement).

Exclusion Criteria:

• Breast cancer patients not undergoing mastectomy

  • Patients undergoing direct-to-implant reconstruction
  • Patients undergoing delayed reconstruction
  • Patients having autologous reconstruction
  • History of radiation to the breast or chest
  • History of previous breast reconstruction on the side of expander placement
  • Patients with serious existing systemic infection, defined as 2 or more of the following: Peripheral body temperature >38 degrees Celsius CRP >5g/L Leukocytes > 12,000/microliter at the time of enrollment.

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: SPD (Arm A); Single pre-operative dose of intravenous antibiotics with intraoperative redosing (SPD): Intravenous cefazolin, a cephalosporin antibiotic, will be prescribed to all patients before surgery. All patients will receive one dose of antibiotic within 60 minutes prior to incision, and any intraoperative doses of antibiotics according to current recommendations based on the antibiotic's dosing and on operative time.	Drug: Single pre-operative dose of intravenous antibiotics with intraoperative redosing; Intravenous cefazolin, a cephalosporin antibiotic, will be prescribed to all patients before surgery. In case of allergy to cefazolin, intravenous clindamycin will be prescribed. For allergy to both antibiotics, an appropriate antibiotic should be chosen by the surgeon and documented. All patients will receive one dose of antibiotic within 60 minutes prior to incision, and any intraoperative doses of antibiotics according to current recommendations based on the antibiotic's dosing and on operative time.
Experimental: WPO (Arm B); The patients assigned to this arm will receive same pre-op and intraoperative antibiotics similar to SPD (Arm A). In addition, patients in this group will receive one week of post-operative antibiotics (WPO). The post-operative antibiotic will be a first generation Cephalosporin of their surgeon's choice.	Drug: Single pre-operative dose of intravenous antibiotics with intraoperative redosing; Intravenous cefazolin, a cephalosporin antibiotic, will be prescribed to all patients before surgery. In case of allergy to cefazolin, intravenous clindamycin will be prescribed. For allergy to both antibiotics, an appropriate antibiotic should be chosen by the surgeon and documented. All patients will receive one dose of antibiotic within 60 minutes prior to incision, and any intraoperative doses of antibiotics according to current recommendations based on the antibiotic's dosing and on operative time.; Drug: One week of post-operative antibiotics; The patients will be prescribed one week of Cephalosporin Antibiotic (Keflex/Duricef/Other) of their surgeon's choice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants in each group who develop surgical site infection (SSI) within 30 days of index procedure.	Surgical site infection as defined by CDC criteria within 30 days after the index procedure	Up to 30 days after the index procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants in each group with antibiotic-related adverse events and the type of adverse events reported.	Antibiotic-related adverse events, e.g. colitis, yeast infections, anaphylaxis, etc.	Up to 30 days after the index procedure
Number of participants in each group who develop an SSI or other complications after 30 days of index procedure.	SSI beyond 30 days after the index procedure up to the time of tissue expander exchange (for an implant or flap)	Up to two years
Number of participants in each group who undergo premature tissue expander or implant removal.	Tissue expander or implant removal, per breast and per patient events will be calculated	From index procedure until expander removal
Type, duration and route of antibiotic administration (Oral or Intravenous) in participants in each group who develop SSI/deep infections.	Antibiotic sensitivities in SSI/deep infections,	Up to two Years
Comparison of any secondary infections, including resistant bacterial strains and yeast infections, in participants from the two groups who develop SSI.	Speciation of any cultures from wound or tissue samples derived from participants in each group who develop SSI will be performed	Up to two Years
ER visit and hospital readmission rates among participants in both groups.	Length of hospitalization, need for surgery, extent of surgery (e.g. wound revision, loss of implant) will be assessed. ER visit and hospitalization rates will be recorded for comparison between the two groups	Up to two Years

Collaborators and Investigators

• Sponsor: The Plastic Surgery Foundation
• Investigators: Principal Investigator: Christine Rohde, MD, MPH, Columbia University; Principal Investigator: Brian Gastman, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2021
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): May 20, 2024

Study Registration Dates

• First Submitted: November 10, 2020
• First Submitted That Met QC Criteria: November 10, 2020
• First Posted (Actual): November 17, 2020

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 24, 2024
• Last Verified: May 1, 2024

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: PSF 19-03-SSI Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The study sites will keep patient details under a study ID number, and not under the patient's name. Aggregate data shared between investigators will be coded and de-identified (except dates).

Drug and device information, study documents

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