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

Major Extremity Trauma Research Consortium

Status and phase: Active, not recruiting; Phase 3

Conditions: Post Operative Surgical Site Infection

Treatments: Drug: Treatment group; Drug: Control group

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT04597008

W81XWH-19-1-0848

Details and patient eligibility

About

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 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.

Enrollment: 1,550 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,550 participants in 2 patient groups

Control

Active Comparator group

Description:

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.

Treatment:

Drug: Control group

Treatment

Experimental group

Description:

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.

Treatment:

Drug: Treatment group