Tobramycin Injection to Prevent Infection in Open Fractures

Surgical Site Infection Clinical Trial

Official title:

Does Prophylactic Local Tobramycin Injection Lower Open Fracture Infection Rates?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04964947
• Other study ID #: 2023P003263
• Secondary ID: GRANT13200494
• Status: Recruiting
• Phase: Phase 3
• Start date: January 10, 2022
• Est. completion date: September 2025

Study information

• Verified date: May 2024
• Source: Massachusetts General Hospital
• Contact: Arun Aneja, MD, PhD
• Phone: 617-726-6546
• Email: aaneja[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Open fracture to arm, leg, or both

• Over the age of 18

Exclusion Criteria:

• Under the age of 18

• Allergy to tobramycin or any other antibiotic in the aminoglycoside family

• Previously treated with a resorbable antibiotic carrier

• Pregnancy

Related Conditions & MeSH terms

• Communicable Diseases
• Fractures, Bone
• Fractures, Open
• Infections
• Surgical Site Infection
• Surgical Wound Infection
• Wound Infection

Intervention

Drug:
• Tobramycin Injection
80 milligrams of tobramycin diluted in 40 milliliters of normal saline

Locations

Country	Name	City	State
United States	University of Kentucky	Lexington	Kentucky
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of infection	Rate of infection one year after open fracture fixation surgery.	1 year
Secondary	Tobramycin effects on non-union	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.	3 months after surgery
Secondary	Tobramycin effects on non-union	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.	6 months after surgery
Secondary	Tobramycin effects on non-union	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.	12 months after surgery
Secondary	Difference in bacterial specification between treatment and standard of care group.	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.	12 months
Secondary	Difference in antibiotic resistance between treatment and standard of care group.	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.	12 months

External Links

•   Pilot Study Results