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

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

The proposed study is a multi-center, prospective randomized controlled trial comparing current standard of care treatment to the SEXTANT treatment protocol in patients with Type III open fractures of the tibia and IIIB fractures of the ankle and hindfoot.

Study Overview

• Status: Recruiting
• Conditions: Post Operative Surgical Site Infection
• Intervention / Treatment: Drug: Standard of care; Drug: Vancomycin and Tobramycin

Detailed Description

Specific Aim 1: 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.

Specific Aim 2: To compare the terminal bioburden of the wounds at the time of definitive closure or coverage as sampled by standard tissue microbiology.

Specific Aim 3: To compare rates of antibiotic-related serious adverse events (SAEs) of the two treatment groups.

Exploratory Aim 4: To pilot the use of available and emerging rapid PCR platforms for wound pathogen identification in a sub-cohort of patients.

• Study Type: Interventional
• Enrollment (Estimated): 1200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Susan C Collins, MSc; Phone Number: 410-502-8966; Email: scolli21@jhu.edu
• Study Contact Backup: Name: Suna Chung, MPH; Phone Number: 4105023357; Email: schung60@jhu.edu

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Recruiting
      • Atrium Health Carolinas Medical Center
      • Contact: Christine Churchill

Participation Criteria

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:

   • Gustilo type III tibia (OTA 41 plateau, OTA 42 shaft and OTA 43 pilon) requiring a second procedure for final debridement and definitive coverage / closure following the index stabilization
   • Gustilo type IIIB ankle fractures (OTA 44)
   • Gustilo type IIIB calcaneus fractures (OTA 82)
   • Gustilo type IIIB talus fractures (OTA 81)
   • 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 transfer to the study institution, as long as the definitive wound closure or 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 infection, with or without antibiotic treatment.
9. Patients may be definitively stabilized using any method (nail, plate, ex fix or cast).
10. Patients may have a fasciotomy.

Exclusion Criteria:

1. Patient in current therapy for a wound, implant or fracture site infection related to the study site.

2. 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
   • Planning to follow-up at another medical center
   • Being a prisoner
   • Not having a means of contact (address, cell phone, home phone, e-mail)

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: Control; Participants in the control group will receive standard of care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection.	Drug: Standard of care; Participants in the control group will receive standard of care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection.
Experimental: Treatment; The patients in the SEXTANT cohort 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. The SEXTANT cohort will then receive at least 72 hours of systemic antibiotic therapy targeted to the modern wound bioburden.	Drug: Vancomycin and Tobramycin; The patients in the SEXTANT cohort 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. The SEXTANT cohort will then receive at least 72 hours of systemic antibiotic therapy targeted to the modern wound bioburden.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Deep surgical site infection	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.	182 days from injury

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Deep surgical site infection	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	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

• 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

Study Major Dates

• Study Start (Actual): May 7, 2021
• Primary Completion (Estimated): September 28, 2024
• Study Completion (Estimated): March 30, 2025

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): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Surgical site infection risk prevention; Bacterial species type and antibacterial sensitivities
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Postoperative Complications; Fractures, Bone; Wounds and Injuries; Wound Infection; Surgical Wound Infection; Fractures, Open; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Tobramycin
• Other Study ID Numbers: W81XWH-19-2-0062

Drug and device information, study documents

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