Tobramycin Injection to Prevent Infection in Open Fractures

Phase 3

Recruiting

• Conditions: Fractures, Open; Surgical Site Infection; Wound Infection
• Interventions: Drug: Tobramycin Injection

• Registration Number: NCT04964947
• Lead Sponsor: Massachusetts General Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-06
• Study First Submitted QC: 2021-07-06
• Study First Posted: 2021-07-16
• Study Start: 2022-01-10
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-30
• Last Update Posted: 2025-05-02
• Primary Completion: 2026-08
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 600

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tobramycin Treatment Group	Tobramycin Injection	Participants in this group receive a local aqueous tobramycin injection (2mg/mL) plus standard of care treatment.

Primary Outcome Measures

Name	Time	Method
Rate of infection	1 year	Rate of infection one year after open fracture fixation surgery.

Secondary Outcome Measures

Name	Time	Method
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.
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.

Trial Locations

Locations (3)

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States