Tobramycin Injection to Prevent Infection in Open Fractures

NCT04964947 | Active Not Recruiting Phase 3 FDA Drug

• 2 other identifiers: 2023P003263GRANT13200494
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 3

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.

Conditions

Wound Infection; Fractures, Open; Surgical Site Infection

Keywords

Local antibiotic; Non-union; Aminoglycoside; Tobramycin; Open extremity fracture; fracture related infection

Outcome Measures

Primary Outcomes (1)

• Rate of infection

  Rate of infection one year after open fracture fixation surgery.

  1 year

Secondary Outcomes (5)

• Tobramycin effects on non-union

  3 months after surgery

• Tobramycin effects on non-union

  6 months after surgery

• Tobramycin effects on non-union

  12 months after surgery

• Difference in bacterial specification between treatment and standard of care group.

  12 months

• Difference in antibiotic resistance between treatment and standard of care group.

  12 months

Study Arms (2)

Tobramycin Treatment Group

EXPERIMENTAL

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

Drug: Tobramycin Injection

Standard of Care Treatment Group

NO INTERVENTION

Participants in this group receive standard of care treatment.

Interventions

Tobramycin Injection DRUG

80 milligrams of tobramycin diluted in 40 milliliters of normal saline

Tobramycin Treatment Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Open fracture to arm, leg, or both
• Over the age of 18

You may not qualify if:

• Under the age of 18
• Allergy to tobramycin or any other antibiotic in the aminoglycoside family
• Previously treated with a resorbable antibiotic carrier
• Pregnancy

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• United States Department of Defense: collaborator

Study Sites (3)

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Links

• Pilot Study Results

MeSH Terms

Conditions

Wound Infection; Fractures, Open; Surgical Wound Infection

Interventions

Tobramycin

Condition Hierarchy (Ancestors)

Infections; Fractures, Bone; Wounds and Injuries; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nebramycin; Kanamycin; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Arun Aneja, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Orthopaedic Trauma Surgeon

Study Record Dates

• First Submitted: July 6, 2021
• First Posted: July 16, 2021
• Study Start: January 10, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)