Tobramycin Injection to Prevent Infection in Open Fractures

Sponsor

Arun Aneja (Other)

Overall Status

Recruiting

CT.gov ID

NCT04964947

Collaborator

United States Department of Defense (U.S. Fed)

300

Enrollment

Location

Arms

43.7

Anticipated Duration (Months)

6.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of open extremity fracture (OEF) treatment is to promote fracture healing and restore function while preventing the development of infection. This is achieved through systematic and timely wound debridement and irrigation, fracture stabilization, tetanus prophylaxis, systemic and local antimicrobial therapy, and judicious timing of wound closure based on cleanliness. Early prophylactic systemic antibiotics lower infection rates in open fractures but have limitations of achieving adequate concentration at the hypoperfused wound area. OEF wounds are frequently poor in vasculature secondary to the soft tissue injury, hence adequate concentration of antibiotic cannot permeate to the tissue at risk. If systemic antibiotic concentrations are increased to achieve minimum inhibitory concentration (MIC) for pathogens at the wound, there is heightened concern for systemic drug toxicity. In sharp contrast, locally administered antibiotics achieve high drug concentration directly within the wound cavity with minimal systemic side effects. Local antibiotic therapy has shown to reduce rates of open fracture wound infection. With the serious implications of postoperative infections in OEF, it is imperative that all measures including further use of prophylactic local antibiotics be considered to prevent fracture-related infection (FRI). The overarching hypothesis for this project is that a novel synergistic combination of local aqueous tobramycin plus perioperative weight-based IV cephalosporin antibiotic prophylaxis will reduce the rate of FRI one year after OEF surgery. This in turn will improve OEF patient outcomes, decreasing morbidity and return to the operating room (OR) without any adverse effect on fracture healing. Regardless of the treatment group, bacterial speciation will be determined for patients that do develop FRI to help guide future treatment. The goal is to improve the clinical outcome and recovery of the population that sustains an OEF by decreasing the rate of FRI and fracture nonunions while concurrently educating on bacterial speciation and resistance.

Condition or Disease	Intervention/Treatment	Phase
Wound Infection Fractures, Open Surgical Site Infection	Drug: Tobramycin Injection	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Does Prophylactic Local Tobramycin Injection Lower Open Fracture Infection Rates?

Actual Study Start Date :

Jan 10, 2022

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tobramycin Treatment Group Participants in this group receive a local aqueous tobramycin injection (2mg/mL) plus standard of care treatment.	Drug: Tobramycin Injection 80 milligrams of tobramycin diluted in 40 milliliters of normal saline
No Intervention: Standard of Care Treatment Group Participants in this group receive standard of care treatment.

Arm

Intervention/Treatment

Experimental: Tobramycin Treatment Group

Participants in this group receive a local aqueous tobramycin injection (2mg/mL) plus standard of care treatment.

Drug: Tobramycin Injection

80 milligrams of tobramycin diluted in 40 milliliters of normal saline

No Intervention: Standard of Care Treatment Group

Participants in this group receive standard of care treatment.

Outcome Measures

Primary Outcome Measures

Rate of infection [1 year]
Rate of infection one year after open fracture fixation surgery.

Secondary Outcome Measures

Tobramycin effects on non-union [3 months after surgery]
Modified radiographic union score for tibial fracture (mRUST) scores combined with clinical observation of functional weight bearing at 3 months will be assessed. If union status remains unclear, nonunion will be further defined as a need for secondary bone grafting or surgical intervention.
Tobramycin effects on non-union [6 months after surgery]
Modified radiographic union score for tibial fracture (mRUST) scores combined with clinical observation of functional weight bearing at 6 months will be assessed. If union status remains unclear, nonunion will be further defined as a need for secondary bone grafting or surgical intervention.
Tobramycin effects on non-union [12 months after surgery]
Modified radiographic union score for tibial fracture (mRUST) scores combined with clinical observation of functional weight bearing at 12 months will be assessed. If union status remains unclear, nonunion will be further defined as a need for secondary bone grafting or surgical intervention.
Difference in bacterial specification between treatment and standard of care group. [12 months]
Upon identification of a fracture-related infection within the first 12 months following surgical fixation, sterile intraoperative cultures will be obtained and grown over 21 days to determine bacterial speciation.
Difference in antibiotic resistance between treatment and standard of care group. [12 months]
Upon identification of a fracture-related infection within the first 12 months following surgical fixation, sterile intraoperative cultures will be obtained and grown over 21 days to determine antimicrobial resistance.