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

Overview

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").

Full Title of Study: “Topical Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: TOBRA – A Multicenter Randomized Controlled Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: September 30, 2024

Detailed Description

Specific Aim 1: Compare the proportion of deep surgical site infections (SSI) of the study injury within 365 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.

Interventions

  • 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 immediately before wound closure.
  • 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 immediately before wound closure.

Arms, Groups and Cohorts

  • 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 immediately before wound closure.
  • 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 immediately before wound closure.

Clinical Trial Outcome Measures

Primary Measures

  • Deep Surgical Site Infection (SSI)
    • Time Frame: within 365 days of definitive fracture fixation surgery
    • Compare the proportion of deep SSIs of the study injury within 365 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.

Secondary Measures

  • Sensitivity analyses
    • Time Frame: within 365 days of definitive fracture fixation surgery
    • 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.
  • Antibiotic resistance
    • Time Frame: within 365 days of definitive fracture fixation surgery
    • 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.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Major Extremity Trauma Research Consortium
  • Collaborator
    • United States Department of Defense
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Robert V O’Toole, MD, MS, Principal Investigator, University of Maryland, Department of Orthopaedic Trauma
    • Renan C Castillo, PhD, Principal Investigator, Johns Hopkins Bloomberg School of Public Health
    • Anthony R Carlini, MS, Study Director, Johns Hopkins Bloomberg School of Public Health
  • Overall Contact(s)
    • Suna Chung, MPH, 410-502-3357, schung60@jhu.edu

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.