Local Antibiotics for Breast Implants (BREAST-AB)

Prophylactic Treatment of Breast Implants With a Solution of Gentamicin, Vancomycin and Cefazolin Antibiotics for Women Undergoing Breast Reconstructive Surgery: a Randomized Controlled Trial (The BREAST-AB Trial)

The BREAST-AB Trial is a multi-center, randomized, double blind, placebo-controlled trial investigating the efficacy of local application of gentamicin, vancomycin and cefazolin in decreasing all-cause implant explantation after breast reconstruction.

Study Overview

• Status: Recruiting
• Conditions: Antibiotic Side Effect; Implant Complication; Implant Site Infection; Implant Infection; Implant Capsular Contracture; Implant Site Pocket Infection; Implant Expulsion
• Intervention / Treatment: Other: Placebo; Drug: Gentamicin, Cefazolin and Vancomycin

Detailed Description

The BREAST-AB Trial will include women undergoing breast reconstruction with implants. The objective is to determine the efficacy of local antibiotics in decreasing all-cause implant explantation. Participants will be randomized to local application of placebo or gentamicin, vancomycin and cefazolin in a saline solution onto the implant and the dissected breast pocket. All patients undergoing unilateral breast reconstruction will be randomized to the trial drug or placebo in a ratio of 1:1. All patients undergoing bilateral reconstruction will be randomized to the trial treatment on one of their breasts and placebo to the contralateral breast. A total number of 1274 of breasts undergoing breast reconstruction will be included in the trial.

• Study Type: Interventional
• Enrollment (Estimated): 1003
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Mikkel Herly, MD, Ph.D.; Phone Number: +45 27598919; Email: mikkel.herly@regionh.dk
• Study Contact Backup: Name: Mathilde Hemmingsen, MD; Phone Number: +45 28568205; Email: mathilde.nejrup.hemmingsen@regionh.dk

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Recruiting
    • Aalborg University Hospital
    • Contact: Lene Birk-Sørensen, MD; Phone Number: +45 97660624; Email: l.birksoerensen@rn.dk
  • Aarhus, Denmark, 8000
    • Recruiting
    • Aarhus University Hospital
    • Contact: Mikkel Rindom, MD; Phone Number: +45 24 60 93 21; Email: MIKKOC@rm.dk
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
    • Contact: Mikkel Herly, MD, Phd; Phone Number: +45 27598919; Email: mikkel.herly@regionh.dk
    • Contact: Mathilde N Hemmingsen, MD; Phone Number: +45 28568205; Email: mathilde.nejrup.hemmingsen@regionh.dk
  • Esbjerg, Denmark, 6700
    • Not yet recruiting
    • South-West Jutland Hospital
    • Contact: Lena F Carstensen, MD; Phone Number: +45 20 15 20 19; Email: Lena.Felicia.Carstensen@rsyd.dk
  • Herlev, Denmark, 2730
    • Recruiting
    • Herlev and Gentofte Hospital
    • Contact: Lisbet R Hölmich, MD, DMSc; Phone Number: +45 27 20 00 14; Email: lisbet.rosenkrantz.hoelmich@regionh.dk
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
    • Contact: Camilla Bille, Phd; Phone Number: +45 65 41 24 45; Email: Camilla.Bille@rsyd.dk
  • Roskilde, Denmark, 4000
    • Recruiting
    • Zealand University Hospital
    • Contact: Michael Rose, MD; Email: mrose@regionsjaelland.dk
  • Vejle, Denmark, 7100
    • Not yet recruiting
    • Vejle Hospital
    • Contact: Bekka Christensen, MD; Email: Bekka.Anina.Ozer.Christensen@rsyd.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age ≥ 18 years
• Biologically female
• Signed informed consent

• Scheduled for breast reconstruction with implants or expanders including:

  1. Immediate or delayed reconstructions
  2. Bilateral or unilateral reconstructions
  3. With or without simultaneous flap reconstruction

Exclusion Criteria:

• Pregnancy
• Breast feeding
• Known allergy towards Vancomycin, Gentamicin and Cefazolin
• Known anaphylactic reaction towards other beta-lactam antibiotics or aminoglycosides
• Known allergy towards neomycin
• Known impaired renal function with GFR < 60 mL/min
• Participation in investigational drug trials and projects concerning disinfecting agents in the breast implant cavity
• Myasthenia Gravis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Irrigation of implants with sterile isotonic saline; The placebo solution will consist of 500 mL of sterile isotonic (9%) saline contained in a infusion bag.	Other: Placebo; 500 mL of sterile isotonic (9%) saline. The solution will be used to wash the dissected implant pocket and the implant prior to insertion in the implant pocket.; Other Names: Natriumklorid Fresenius Kabi 9 mg-ml
Experimental: Irrigation of implants with a triple antibiotic solution; The antibiotic solution will contain 1000 mg vancomycin, 80 mg gentamicin and 1000 mg cefazolin in 500 mL sterile isotonic (9%) saline	Drug: Gentamicin, Cefazolin and Vancomycin; The antibiotic solution will contain 1000 mg vancomycin, 80 mg gentamicin and 1000 mg cefazolin in a 500 mL isotonic saline solution. The solution will be used to wash the dissected implant pocket and the implant prior to insertion in the implant pocket.; Other Names: Hexamycin, Cefazolin "MIP" and Bactocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause explantation of the breast implant after the breast reconstruction surgery	All-cause explantation will be defined as explantation and discarding of the implant. Replacement of an expander with a permanent implant and replacement of a permanent breast implant with a new permanent breast implant due to cosmetic revisions such as asymmetry, implant malposition, change of size or implant rotation will not be counted as an explantation.	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to explantation (days)	Time to explantation will be defined as the amount of days between the breast reconstruction and the implant explantation surgery.	180 days
Revision surgery with incision of the fibrous capsule after the breast reconstruction surgery (Y/N)	The breast reconstruction surgery will be defined as the surgery where they received the allocated treatment	180 days
Exchange of permanent implant to expander implant after the breast reconstruction surgery (Y/N)	The breast reconstruction surgery will be defined as the surgery where they received the allocated treatment	180 days
Surgical site infection that leads to antibiotic treatment after the breast reconstruction surgery	Surgical site infection will be defined according to the CDC classification of surgical site infetion leading to antibiotic treatment with oral or intravenous antibiotics administered after the surgery.	180 days
All-cause explantation of the breast implant within 1 year after the breast reconstruction surgery	All-cause explantation will be defined as explantation and discarding of the implant. Replacement of an expander with a permanent implant and replacement of a permanent breast implant with a new permanent breast implant due to cosmetic revisions such as asymmetry, implant malposition, change of size or implant rotation will not be counted as an explantation.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from the breast reconstruction surgery to discharge (days)	Time to discharge will be defined as the amount of days between the breast reconstruction and the day of discharge.	180 days
Re-admission after the breast reconstruction surgery (Y/N)	The breast reconstruction surgery will be defined as the surgery where the patient received the allocated treatment.	180 days
Long term follow-up after 5, 10 and 15 years	Capsular contracture and the Baker classification grade will be obtained from the National Patient Registry and the patients' medical journals after 5, 10 and 15 years. The BREAST-Q questionnaire will be used to assess patient-reported outcomes. The patients will be contacted and asked to fill out the questionnaire with 5 year-intervals after the surgery.	15 years

Collaborators and Investigators

• Sponsor: Mikkel Herly
• Collaborators: Odense University Hospital; Zealand University Hospital; Aarhus University Hospital; University of Copenhagen; Vejle Hospital; Aalborg University Hospital; Herlev and Gentofte Hospital; Hospital of South West Jutland
• Investigators: Principal Investigator: Mikkel Herly, MD, Ph.D., Department of Plastic Surgery and Burns Treatment

Publications and helpful links

General Publications

• Hemmingsen MN, Larsen A, Weltz TK, Orholt M, Wiberg S, Bennedsen AK, Bille C, Carstensen LF, Jensen LT, Bredgaard R, Koudahl V, Schmidt VJ, Vester-Glowinski P, Holmich LR, Sorensen SJ, Bjarnsholt T, Damsgaard T, Herly M. Prophylactic treatment of breast implants with a solution of gentamicin, vancomycin and cefazolin antibiotics for women undergoing breast reconstructive surgery: protocol for a randomised, double-blind, placebo-controlled trial (The BREAST-AB trial). BMJ Open. 2022 Sep 17;12(9):e058697. doi: 10.1136/bmjopen-2021-058697.

Helpful Links

• Study protocol published in BMJ Open

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2021
• Primary Completion (Estimated): July 27, 2025
• Study Completion (Estimated): January 27, 2026

Study Registration Dates

• First Submitted: January 26, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): January 29, 2021

Study Record Updates

• Last Update Posted (Estimated): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Postoperative Complications; Disease Attributes; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Foreign-Body Reaction; Prosthesis Failure; Infections; Communicable Diseases; Contracture; Implant Capsular Contracture; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Vancomycin; Gentamicins; Cefazolin
• Other Study ID Numbers: BREAST-AB-01; 2020-002459-40 (EudraCT Number); 0058322 (Other Grant/Funding Number: Novo Nordisk Foundation); R-189- A4127 (Other Grant/Funding Number: Medicine Fund of the Danish Regions)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The protocol including the statistical analysis plan is published in BMJ Open (doi:10.1136/bmjopen-2021-058697) prior to unblinding. The main article will include the primary and secondary outcomes. The tertiary and long-term outcomes will be included in subsequent articles. The manuscripts will be submitted to peer-reviewed international journals and both positive, negative and inconclusive results will be published. The findings of the trial will be shared with participating sites and presented at national and international conferences. The results will be disseminated to the public but will not be shared directly with participating patients.
• IPD Sharing Time Frame: After the end of the trial, the data will become available (Anticipated july 2025)
• IPD Sharing Access Criteria: Researchers and other relevant parties can be granted access to selected anonymized data after publication upon request to the principal-sponsor investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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