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

NCT04678154 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: H294252510976
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 31

Brief Summary

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.

Conditions

Post Operative Surgical Site Infection

Keywords

Surgical site infection risk prevention; Bacterial species type and antibacterial sensitivities

Outcome Measures

Primary Outcomes (1)

• Deep surgical site infection

  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

Study Arms (2)

Control

ACTIVE COMPARATOR

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

Treatment

EXPERIMENTAL

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

Interventions

Standard of care DRUG

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.

Control

Vancomycin and Tobramycin DRUG

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.

Treatment

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Ages 18 - 64 years inclusive
• Patients may have risk factors for infection including diabetes, immunosuppression from steroids or other medications, HIV, or other infections.
• Patients may have a traumatic brain injury.
• Patients may have other fractures including spine, upper extremity fractures, contralateral lower extremity injuries, ipsilateral pelvis, hip, femur, or foot injuries.
• 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.
• Patients may have co-existing non-tibial or hindfoot infections, with or without antibiotic treatment.
• Patients may be definitively stabilized using any method (nail, plate, ex fix, or cast).
• Patients may have fasciotomy.

You may not qualify if:

• Patient speaks neither English or Spanish
• Patient in current therapy for a wound, implant or fracture site infection related to the study site.
• Patient is pregnant, potentially pregnant, or lactating.
• Patient likely to have difficulty maintaining follow-up, including:
• Diagnosis of a severe psychiatric condition
• Intellectually challenged without adequate family support
• Resides outside of the hospital's catchment area, unless willing to follow-up by phone or telemedicine
• Planning to follow-up at another medical center, unless willing to follow-up by phone or telemedicine
• Being a prisoner
• Not having a means of contact (address, cell phone, home phone, e-mail)

Sponsors & Collaborators

• Major Extremity Trauma Research Consortium: lead
• United States Department of Defense: collaborator

Study Sites (31)

Stanford University

Redwood City, California, 94063, United States

RECRUITING

_University of California, San Francisco

San Francisco, California, 94110, United States

RECRUITING

University of California at San Francisco

San Francisco, California, 94110, United States

RECRUITING

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

St Mary's University/Tenent Health

West Palm Beach, Florida, 33407, United States

RECRUITING

Emory University School of Medicine

Atlanta, Georgia, 30303, United States

RECRUITING

Indiana University School of Medicine - Methodist Hospital

Indianapolis, Indiana, 46202, United States

RECRUITING

Indiana University/Eskenazi Health

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Kentucky

Lexington, Kentucky, 40506, United States

RECRUITING

LSU Health Sciences

New Orleans, Louisiana, 70112, United States

RECRUITING

University of Maryland , MD Department of Orthopaedics

Baltimore, Maryland, 21201, United States

RECRUITING

Walter Reed Military Medical Center

Bethesda, Maryland, 20889, United States

RECRUITING

Harvard/Mass General/Brigham Hospitals

Boston, Massachusetts, 02115, United States

RECRUITING

Hennepin County Medical Center / Minneapolis

Minneapolis, Minnesota, 55415, United States

RECRUITING

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

RECRUITING

Dartmouth Hitchcock

Lebanon, New Hampshire, 03766, United States

RECRUITING

Jamaica Hospital Medical Center

Jamaica, New York, 11418, United States

RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

RECRUITING

Atrium Health Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

RECRUITING

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, 27157, United States

RECRUITING

METROHealth

Cleveland, Ohio, 44109, United States

RECRUITING

Ohio State University Wexner Medical Center

Columbus, Ohio, 43201, United States

RECRUITING

University of Oklahoma College of Medicine

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Temple University

Philadelphia, Pennsylvania, 19140, United States

RECRUITING

Brown University/Rhode Island Hospital

Providence, Rhode Island, 02905, United States

RECRUITING

Rhode Island Hospital/Brown University

Providence, Rhode Island, 02905, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

University of Texas Health Science Center - Houston

Houston, Texas, 77030, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

Inova Fairfax MEdical Campus

Falls Church, Virginia, 22042, United States

RECRUITING

Virginia Commonwealth University Medical Center

Richmond, Virginia, 23298, United States

RECRUITING

MeSH Terms

Interventions

Standard of Care; Vancomycin; Tobramycin

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Nebramycin; Kanamycin; Aminoglycosides; Glycosides

Study Officials

• Micahel J Bosse, MD

  Carolinas Medical Center

  PRINCIPAL INVESTIGATOR

• Rachel Seymour, PhD

  Atrium Health Musculoskeletal Institute Research

  PRINCIPAL INVESTIGATOR

• Renan C Castillo, PhD

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

• Anthony R Carlini, MS

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Suna Chung, MPH

CONTACT

4105023357; schung60@jhu.edu

Susan C Collins, MSc

CONTACT

410-502-8966; scolli21@jhu.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2020
• First Posted: December 21, 2020
• Study Start: May 7, 2021
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: July 22, 2026

Record last verified: 2026-06

Locations

US (31)