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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Post Operative Surgical Site Infection

Intervention / Treatment
-----------------
* Drug: Standard of care
* Drug: Vancomycin and Tobramycin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 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 transfer to the study institution, as long as the definitive wound closure or coverage was not performed prior to entrance into the study. 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. Patients may have co-existing non-tibial or hindfoot infection, with or without antibiotic treatment. Patients may be definitively stabilized using any method (nail, plate, ex fix or cast). Patients may have a fasciotomy. Exclusion Criteria: Patient in current therapy for a wound, implant or fracture site infection related to the study site. 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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>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<br>* 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.<br>|
| Experimental: Treatment<br>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<br>* 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.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Surgical site infection risk prevention, Bacterial species type and antibacterial sensitivities