Evaluation of a New Strategy for Protocolized Antibiotic Care for Severe Open Fractures: SEXTANT 2 (SEXTANT 2)

July 20, 2026 updated by: Major Extremity Trauma Research Consortium

Evaluation of a New Strategy for Protocolized Antibiotic Care for Severe Open Fractures: SEXTANT 2 - A Continuation of the Multicenter Randomized Control Trial SEXTANT 1

The PRCT evaluates infection outcomes as well as fracture and antibiotic-related complications to include the emergence of resistant bacteria associated with two different antibiotic strategies in the treatment of Gustilo type IIIB tibia and hindfoot fractures (calcaneus and talus) and selected IIIA fractures of the tibia and trauma-related transtibial amputations that are performed in the "zone-of-injury". This study will be conducted in established METRC level 1 trauma centers.

The patients will be randomized as close to admission as possible to either 1) Standard of Care (SOC) prophylactic open fracture protocol, including the use of topical antibiotic as per the usual practice of the surgeon or 2) experimental protocol (SEXTANT). The SEXTANT protocol includes application of wound bioburden-targeted topical Vancomycin powder and Tobramycin powder antibiotic treatment at the time of final wound closure/coverage combined with 72 hours of systemic antibiotic coverage targeted to both gram-positive and gram-negative pathogens. The study will compare the results of the current SOC prophylactic coverage to the strategic wound bioburden treatment (SEXTANT) protocol.

Up until the time of definitive wound closure/coverage, all patients will be treated per the usual regimen of the surgeon / center and in accordance with current Trauma Quality Improvement Program (TQIP) and Surgical Quality Improvement Program (SQIP) recommendations for the care of open fractures.14,15,17 It includes the administration of systemic antibiotics as close to the time of injury as possible.

In the definitive wound closure/coverage procedure post-operative period, participants in the intervention arm will receive 72 hours of systemic antibiotic therapy targeted at the modern wound bioburden, and patients in the usual care arm will receive post-operative care per the usual practice of their surgeon. All other activities related to follow-up and related treatments will proceed per the usual practice of the surgeon.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Specific Aim 1: To determine if the SEXTANT treatment strategy designed to address the modern wound bioburden at the time of delayed wound closure/coverage is superior to the standard-of-care (SOC) antibiotic protocol. Our primary comparison will be the proportion of fracture-related infections (FRI) under the SEXTANT arm versus the FRI proportion for those under standard of care in the first 180 days following final wound closure/coverage. One-year rates of FRI will also be assessed.

Secondary Aims:

To compare rates of antibiotic-related complications (including aseptic nonunion) and serious adverse events (SAEs), including emergence of antibiotic-resistant pathogens, of the two treatment groups in the first 180 days following final wound closure/coverage. One-year rates will also be assessed.

To compare the terminal bioburden of the wounds at the time of delayed closure/coverage as sampled by standard tissue microbiology and assess the effectiveness of the antibiotic regimen.

(Exploratory) To employ emerging NextGen Sequencing rapid PCR platforms for wound pathogen identification in a sub-cohort of patients.

Study Type

Interventional

Enrollment (Estimated)

600

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Redwood City, California, United States, 94063
        • Recruiting
        • Stanford University
        • Contact:
      • San Francisco, California, United States, 94110
        • Recruiting
        • _University of California, San Francisco
        • Contact:
      • San Francisco, California, United States, 94110
        • Recruiting
        • University of California at San Francisco
        • Contact:
        • Principal Investigator:
          • Saam Morshed, MD
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Anschutz Medical Campus
        • Contact:
    • Florida
      • West Palm Beach, Florida, United States, 33407
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Recruiting
        • Emory University School of Medicine
        • Principal Investigator:
          • William Reisman, MD
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University School of Medicine - Methodist Hospital
        • Contact:
          • Maricella Diaz
          • Phone Number: 317.963.5034
          • Email: diaz4@iu.edu
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University/Eskenazi Health
        • Contact:
    • Kentucky
      • Lexington, Kentucky, United States, 40506
        • Recruiting
        • University of Kentucky
        • Contact:
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland , MD Department of Orthopaedics
        • Principal Investigator:
          • Robert O'Toole, MD
        • Contact:
      • Bethesda, Maryland, United States, 20889
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
    • Minnesota
      • Minneapolis, Minnesota, United States, 55415
        • Recruiting
        • Hennepin County Medical Center / Minneapolis
        • Principal Investigator:
          • Andrew Schmidt, MD
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • Recruiting
        • University of Mississippi Medical Center
        • Contact:
    • New Hampshire
    • New York
      • Jamaica, New York, United States, 11418
        • Recruiting
        • Jamaica Hospital Medical Center
        • Principal Investigator:
          • Sanjit Konda, MD
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
      • Charlotte, North Carolina, United States, 28203
        • Recruiting
        • Atrium Health Carolinas Medical Center
        • Contact:
          • Christine Churchill
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Atrium Health Wake Forest Baptist
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44109
      • Columbus, Ohio, United States, 43201
        • Recruiting
        • Ohio State University Wexner Medical Center
        • Contact:
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma College of Medicine
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • Recruiting
        • Brown University/Rhode Island Hospital
        • Principal Investigator:
          • Roman Hayda, MD
      • Providence, Rhode Island, United States, 02905
        • Recruiting
        • Rhode Island Hospital/Brown University
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University Medical Center
        • Contact:
        • Principal Investigator:
          • William T. Obremskey, MD
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas Health Science Center - Houston
        • Contact:
        • Principal Investigator:
          • Stephen Warner, MD
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • University of Virginia
        • Principal Investigator:
          • David Weiss, MD
        • Contact:
      • Falls Church, Virginia, United States, 22042
        • Recruiting
        • Inova Fairfax MEdical Campus
        • Contact:
      • Richmond, Virginia, United States, 23298

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 64 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Injury meeting at least one of the following criteria:

    a. Gustilo type III fractures of the tibia (OTA 41 plateau, OTA 42 shaft and OTA 43 pilon); ankle (OTA 44); calcaneus (OTA 82) and/or talus (OTA 81) with injury characteristics meeting at least one of the following criteria: i. All IIIB fractures ii. IIIA fractures that require a planned second debridement prior to definitive closure / coverage iii. IIIA fractures with extensive contamination or muscle damage precluding definitive internal fixation at the time of initial surgery iv. IIIA fractures with extensive degloving or wound greater than 10 cm after debridement (if indicated, primary wound closure is allowed. Primary wound closure refers to the definitive closure of the wound at the initial surgical event, without plans for re-entry for additional debridement and/or fracture fixation) v. IIIA fractures severe fracture comminution resulting from high energy trauma (if indicated, primary wound closure/coverage is allowed) vi. IIIA fractures with AO/OTA OFC contamination level of severe with material imbedded into bone or soft tissue or with a severe high risk environmental contamination from farm, fecal, dirty water inoculation or other equivalent (if indicated, primary wound closure/coverage is allowed) vii. IIIA Fractures where the skin could be closed after extensive muscle or bone removal (if indicated, primary wound closure/coverage is allowed) viii. IIIA fractures with bone loss resulting in a circumferential gap of 1 cm after debridement (if indicated, primary wound closure/coverage is allowed) ix. Fractures where fasciotomies were performed for impending or diagnosed compartment syndromes (regardless of the initial open or closed classification of the fracture x. Traumatic "zone-of-injury" trans-tibial amputations requiring DPC, and/or flap coverage

  2. Ages 18 - 64 years inclusive
  3. Patients may have risk factors for infection including diabetes, immunosuppression from steroids or other medications, HIV, or other infections.
  4. Patients may have a traumatic brain injury.
  5. Patients may have other fractures including spine, upper extremity fractures, contralateral lower extremity injuries, ipsilateral pelvis, hip, femur, or foot injuries.
  6. Patients may be treated initially at an outside institution prior to transferring to the study institution, as long as the definitive wound closure/coverage was not performed prior to entrance into the study.
  7. Patients with bilateral injuries that meet inclusion criteria may be included, but only the limb rated as "more severe" by the treating surgeon will be enrolled in the study.
  8. Patients may have co-existing non-tibial or hindfoot infections, with or without antibiotic treatment.
  9. Patients may be definitively stabilized using any method (nail, plate, ex fix, or cast).
  10. Patients may have fasciotomy.

Exclusion Criteria:

  1. Patient speaks neither English or Spanish
  2. Patient in current therapy for a wound, implant or fracture site infection related to the study site.
  3. Patient is pregnant, potentially pregnant, or lactating.

  4. Patient likely to have difficulty maintaining follow-up, including:

    1. Diagnosis of a severe psychiatric condition
    2. Intellectually challenged without adequate family support
    3. Resides outside of the hospital's catchment area, unless willing to follow-up by phone or telemedicine
    4. Planning to follow-up at another medical center, unless willing to follow-up by phone or telemedicine
    5. Being a prisoner
    6. Not having a means of contact (address, cell phone, home phone, e-mail)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Control
Participants in the control group will receive standard care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection. Topical antibiotics are allowed, if SOC for the institution, but are not mandated.
Drug: Standard of care
Participants in the control group will receive standard care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection. Topical antibiotics are allowed, if SOC for the institution, but are not mandated.
Experimental: Treatment
The patients in the SEXTANT cohort will receive 72 hours of targeted systemic antibiotic therapy (Table 2) and will have 1000 mg of Vancomycin and 1200 mg of Tobramycin administered to the wound surface, fracture site, and exposed hardware (if any) just prior to suture closure of the wound or flap.
Drug: Vancomycin and Tobramycin

The patients in the SEXTANT cohort will receive 72 hours of targeted systemic antibiotic therapy (Table 2) and will have 1000 mg of Vancomycin and 1200 mg of Tobramycin administered to the wound surface, fracture site, and exposed hardware (if any) just prior to suture closure of the wound or flap.

72-hour of systemic gram-positive and gram-negative antibiotic coverage to target the terminal wound bioburden. The antibiotics coverage proposed as the primary choice includes PO Ciprofloxacin + PO linezolid or IV Ciprofloxacin and IV Vancomycin.

The preferred antibiotic regimen will be decided by study's ID team, in cooperation with the ID and Antibiotic Stewardship teams at each site. Antibiotic recommendations will be adjusted, if needed, to account for a Site's bacteria susceptibility / resistance profile, or the specific needs of an individual patient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Deep surgical site infection
Time Frame: 180 days from final wound closure/cloverage
To determine if the SEXTANT treatment strategy designed to address the modern wound bioburden at the time of delayed wound closure/coverage is superior to the standard-of-care (SOC) antibiotic protocol. Our primary comparison will be the proportion of fracture-related infections (FRI) under the SEXTANT arm versus the FRI proportion for those under standard of care in the first 180 days following final wound closure/coverage. One-year rates of FRI will also be assessed.
180 days from final wound closure/cloverage

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Deep surgical site infection
Time Frame: 365 days from injury
To compare the surgical site infection (SSI) rates of the current severe open fracture antibiotic strategy to a revised SEXTANT treatment strategy designed to address the modern wound bioburden at the time of wound closure or coverage.
365 days from injury
Fracture revision rates
Time Frame: 365 days from injury
Fracture revision rates for non-union, flap failure, amputation, the development of resistant bacteria discovered at revision surgery and antibiotic-related complications (C. difficile, nephrotoxicity, ototoxicity).
365 days from injury

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Major Extremity Trauma Research Consortium

Collaborators

United States Department of Defense

Investigators

  • Principal Investigator: Micahel J Bosse, MD, Carolinas Medical Center
  • Principal Investigator: Rachel Seymour, PhD, Atrium Health Musculoskeletal Institute Research
  • Principal Investigator: Anthony R Carlini, MS, Johns Hopkins Bloomberg School of Public Health
  • Principal Investigator: Renan C Castillo, PhD, Johns Hopkins Bloomberg School of Public Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 7, 2021

Primary Completion (Estimated)

September 30, 2028

Study Completion (Estimated)

March 31, 2029

Study Registration Dates

First Submitted

December 11, 2020

First Submitted That Met QC Criteria

December 18, 2020

First Posted (Actual)

December 21, 2020

Study Record Updates

Last Update Posted (Actual)

July 22, 2026

Last Update Submitted That Met QC Criteria

July 20, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H294252510976

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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