Topical Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: TOBRA (TOBRA)

Topical Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: TOBRA - A Multicenter Randomized Controlled Trial

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").

Study Overview

• Status: Completed
• Conditions: Post Operative Surgical Site Infection
• Intervention / Treatment: Drug: Control group; Drug: Treatment group

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 only gram-negative bacteria, infection by any gram-positive bacteria (with or without other organisms of any type), 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.

• Study Type: Interventional
• Enrollment (Actual): 1550
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • University of Alabama Heersink School of Medicine
  • California
    • Los Angeles, California, United States, 90033
      • Keck School of Medicine of USC
    • Redwood City, California, United States, 94063
      • Stanford University
    • San Francisco, California, United States, 94110
      • _University of California, San Francisco
    • West Hollywood, California, United States, 90069
      • Cedars Sinai
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus
  • Florida
    • West Palm Beach, Florida, United States, 33407
      • St Mary's University/Tenent Health
  • Illinois
    • Chicago, Illinois, United States, 60153
      • Loyola University Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine - Methodist Hospital
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Eskenazi Health
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • University of Kentucky
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • LSU Health Sciences
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Shock Trauma Center
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Shock Trauma/Capitol Regions
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Harvard/Mass General/Brigham Hospitals
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Core Well Health
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth Hitchcock
  • New York
    • New York, New York, United States, 10021
      • New York Presbyterian/Hospital for Special Surgery
    • Queens, New York, United States, 11418
      • Jamaica Hospital Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina at Chapel Hill
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center/Atrium Health Musculoskeletal Health Institute
    • Winston-Salem, North Carolina, United States, 27157
      • Atrium Health Wake Forest Baptist
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth
    • Columbus, Ohio, United States, 43201
      • Ohio State University Wexner Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma College of Medicine
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State College of Medicine
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
    • Philadelphia, Pennsylvania, United States, 19106
      • University of Pennsylvania Perelman School of Medicine
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Rhode Island Hospital/Brown University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina -
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Scott & White Research Institute
    • Houston, Texas, United States, 77030
      • UTHealth/McGovern Medical School
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Medical Campus
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.
• Patients ages 18 through 80 years.

Exclusion Criteria:

• Study injury is already infected at time of study enrollment.
• Definitive fixation of the study injury prior to enrollment in the study.
• The patient never receives study fixation.
• Massive myonecrosis from ipsilateral leg compartment syndrome.
• Currently pregnant.
• 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).
• Patients with allergies, drug administration reactions, or other sensitivities to Vancomycin (such as a history of Redman's Syndrome).
• Patients with allergies, drug administration reactions, or other sensitivities to Tobramycin or other aminoglycosides.

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; Standard of Care + Local Vancomycin: Participants in the control group will receive a dose of 1000mg of Vancomycin powder in their wound bed, which is placed right before wound closure at the final stage of definitive fracture fixation.	Drug: Control group; Standard of Care + Local Vancomycin: Participants in the control group will receive a dose of 1000mg of Vancomycin powder in their wound bed, which is placed right before wound closure at the final stage of definitive fracture fixation.; Other Names: Control
Experimental: Treatment; Standard of Care + Local Vancomycin + Local Tobramycin: Participants in the treatment group will receive a dose of 1000mg of Vancomycin powder AND a dose of 1200mg of Tobramycin powder in their wound bed, which is placed right before wound closure at the final stafe of definitive fracture fixation.	Drug: Treatment group; Standard of Care + Local Vancomycin + Local Tobramycin: Participants in the treatment group will receive a dose of 1000mg of Vancomycin powder AND a dose of 1200mg of Tobramycin powder in their wound bed, which is placed right before wound closure at the final stafe of definitive fracture fixation.; Other Names: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Deep Surgical Site Infection (SSI)	Compare the proportion of deep SSIs of the study injury within 182 days of definitive fracture fixation surgery in patients treated with local Vancomycin powder compared to those treated with a combination of local Vancomycin and Tobramycin powders. For this study a "deep SSI" is a SSI that is treated with operative debridement. In the current CDC terminology this would include all deep organ space, deep incisional, and superficial infections that are treated with surgery.	within 182 days of definitive fracture fixation surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity analyses	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.	within 365 days of definitive fracture fixation surgery
Antibiotic resistance	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.	within 365 days of definitive fracture fixation surgery

Collaborators and Investigators

• Sponsor: Major Extremity Trauma Research Consortium
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Robert V O'Toole, MD, MS, University of Maryland, Department of Orthopaedic Trauma; Study Director: Anthony R Carlini, MS, Johns Hopkins Bloomberg School of Public Health; Principal Investigator: Renan C Castillo, PhD, Johns Hopkins Bloomberg School of Public Health

Publications and helpful links

General Publications

• Schrank GM, O'Hara NN, Lee S, Degani Y, Chung S, Carlini AR, Castillo RC, O'Toole RV. Safety of topical tobramycin powder during operative treatment of fractures. J Antimicrob Chemother. 2025 Sep 3;80(9):2417-2420. doi: 10.1093/jac/dkaf230.

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2021
• Primary Completion (Actual): July 30, 2025
• Study Completion (Actual): July 30, 2025

Study Registration Dates

• First Submitted: October 15, 2020
• First Submitted That Met QC Criteria: October 15, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Surgical site infection risk prevention; Bacterial species type and antibacterial sensitivities
• Additional Relevant MeSH Terms: Postoperative Complications; Pathologic Processes; Disease Attributes; Wound Infection; Infections; Communicable Diseases; Surgical Wound Infection; Investigative Techniques; Epidemiologic Research Design; Epidemiologic Methods; Research Design; Methods; Control Groups; Therapeutics
• Other Study ID Numbers: W81XWH-19-1-0848

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