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

Post Operative Surgical Site Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04597008
• Other study ID #: W81XWH-19-1-0848
• Status: Recruiting
• Phase: Phase 3
• Start date: May 11, 2021
• Est. completion date: March 31, 2026

Study information

• Verified date: December 2023
• Source: Major Extremity Trauma Research Consortium
• Contact: Suna Chung, MPH
• Phone: 410-502-3357
• Email: schung60[@]jhu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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").

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1900
• Est. completion date: March 31, 2026
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Post Operative Surgical Site Infection
• Surgical Wound Infection

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	University of Maryland Shock Trauma Center	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Major Extremity Trauma Research Consortium	United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Deep Surgical Site Infection (SSI)	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.	within 365 days of definitive fracture fixation surgery
Secondary	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
Secondary	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