Clinical trial NCT04964947: Tobramycin Injection to Prevent Infection in Open Fractures
Official title: Does Prophylactic Local Tobramycin Injection Lower Open Fracture Infection Rates?
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Wound Infection
Fractures, Open
Surgical Site Infection
Keywords: Local antibiotic
Non-union
Aminoglycoside
Tobramycin
Open extremity fracture
fracture related infection
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2021-07-16
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Rate of infection
timeFrame: 1 year
Secondary outcomes:
measure: Tobramycin effects on non-union
timeFrame: 3 months after surgery
measure: Tobramycin effects on non-union
timeFrame: 6 months after surgery
measure: Tobramycin effects on non-union
timeFrame: 12 months after surgery
measure: Difference in bacterial specification between treatment and standard of care group.
timeFrame: 12 months
measure: Difference in antibiotic resistance between treatment and standard of care group.
timeFrame: 12 months
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Massachusetts General Hospital
name: Arun Aneja, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: