Tobramycin Injection to Prevent Infection in Open Fractures

Mass General Brigham

Status and phase: Enrolling; Phase 3

Conditions: Fractures, Open; Surgical Site Infection; Wound Infection

Treatments: Drug: Tobramycin Injection

Study type: Interventional

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

Identifiers

NCT04964947

2023P003263

GRANT13200494 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Enrollment: 600 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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600 participants in 2 patient groups

Tobramycin Treatment Group

Experimental group

Description:

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

Treatment:

Drug: Tobramycin Injection

Standard of Care Treatment Group

No Intervention group

Description:

Participants in this group receive standard of care treatment.