Clinical trial NCT04597008: Topical Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: TOBRA
Official title: Topical Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: TOBRA - A Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Post Operative Surgical Site Infection
Keywords: Surgical site infection risk prevention
Bacterial species type and antibacterial sensitivities
Lead sponsor: Major Extremity Trauma Research Consortium
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2020-10-22
Enrollment: 1900
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The overall objective is to compare the effect of Vancomycin and Tobramycin powder combined (treatment) to Vancomycin powder (control) in the reduction of post-fixation infections of tibial plateau and tibial pilon fractures at high risk of infection (collectively considered the "study injuries").

Detailed description: Specific Aim 1: Compare the proportion of deep surgical site infections (SSI) of the study injury within 182 days of definitive fracture fixation surgery in patients allocated to receive a combination of local Vancomycin and Tobramycin powders compared to patients allocated to local Vancomycin powder.

Sensitivity Analyses: A series of sensitivity analyses will be conducted to look at alternative measures of deep SSI under Specific Aim 1. These sensitivity analyses will consider the following alternative end points of deep SSI: infection by gram-negative bacteria, infection by gram-positive bacteria, polymicrobial pathogenic infections, culture negative infections, and cellulitis/skin infections.

Specific Aim 2: To compare the safety of treatment with a combination of local Vancomycin and Tobramycin versus Vancomycin powder alone as measured by the proportion of antibiotic resistance in each arm.

Eligibility criteria: Inclusion Criteria:

1. Tibial plateau or tibial pilon fractures that is treated operatively with plate and screw fixation AND at least one of the following characteristics indicative of higher risk of infection:

   1. Initially treated with an external fixation and treated definitively more than 3 days later after swelling has resolved.
   2. Any open type I, II, or IIIA fracture, regardless of timing of definitive treatment.
   3. Tibia fracture is associated with ipsilateral leg compartment syndrome and fasciotomy wounds.
2. Patients ages 18 through 80 years.

Exclusion Criteria:

1. Study injury is already infected at time of study enrollment.
2. Definitive fixation of the study injury prior to enrollment in the study.
3. The patient never receives study fixation.
4. Massive myonecrosis from ipsilateral leg compartment syndrome.
5. Currently pregnant.
6. Severe problems with maintaining follow-up (e.g. patients who are homeless at the time of injury, those who are intellectually challenged without adequate family support, or are unwilling to provide phone and address contact information).
7. Patients with allergies, drug administration reactions, or other sensitivities to Vancomycin (such as a history of Redman's Syndrome).
8. Patients with allergies, drug administration reactions, or other sensitivities to Tobramycin or other aminoglycosides.

Primary outcomes:
measure: Deep Surgical Site Infection (SSI)
timeFrame: within 182 days of definitive fracture fixation surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Heersink School of Medicine
state: Alabama
city: Los Angeles
country: United States
facility: Keck School of Medicine of USC
state: California
city: Redwood City
country: United States
facility: Stanford University
state: California
city: San Francisco
country: United States
facility: _University of California, San Francisco
state: California
city: West Hollywood
country: United States
facility: Cedars Sinai
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: West Palm Beach
country: United States
facility: St Mary's University/Tenent Health
state: Florida
city: Chicago
country: United States
facility: Loyola University Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine - Methodist Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University/Eskenazi Health
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: LSU Health Sciences
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Shock Trauma Center
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland Shock Trauma/Capitol Regions
state: Maryland
city: Boston
country: United States
facility: Harvard/Mass General/Brigham Hospitals
state: Massachusetts
city: Grand Rapids
country: United States
facility: Core Well Health
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Lebanon
country: United States
facility: Dartmouth Hitchcock
state: New Hampshire
city: New York
country: United States
facility: New York Presbyterian/Hospital for Special Surgery
state: New York
city: Queens
country: United States
facility: Jamaica Hospital Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center/Atrium Health Musculoskeletal Health Institute
state: North Carolina
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist
state: North Carolina
city: Cleveland
country: United States
facility: METROHealth
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma College of Medicine
state: Oklahoma
city: Hershey
country: United States
facility: Penn State College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Perelman School of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital/Brown University
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina -
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: Baylor Scott & White Research Institute
state: Texas
city: Houston
country: United States
facility: UTHealth/McGovern Medical School
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax MEdical Campus
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Maryland, Department of Orthopaedic Trauma
name: Robert V O'Toole, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Renan C Castillo, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Anthony R Carlini, MS
role: STUDY_DIRECTOR
References: