Clinical trial NCT05157126: Gentamicin Open Tibia Study
Official title: A Masked, Randomized Controlled Trial Evaluating Locally-applied Gentamicin Versus Saline in Open Tibia Fractures
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Fracture Open Tibia
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Muhimbili Orthopaedic Institute
name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
name: Orthopedic Research and Education Foundation
First posted: 2021-12-14
Enrollment: 890
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single-center individually-randomized placebo-controlled superiority trial
Primary purpose: PREVENTION

Brief summary: Local application of antibiotics directly to the traumatic wound is a promising treatment for the prevention of infection after open tibia fractures, which are a significant source of disease burden globally, particularly in low-income countries. This study aims to measure the effect of locally applied gentamicin on risk of infection for open tibial fractures in Tanzania. If proven effective, local gentamicin would be a highly cost-effective strategy to reduce complications and disability from open tibial fractures that could impact care in both high- and low-income countries.

Detailed description: Tibial shaft (shinbone) fractures are the most common major fracture of the lower leg and are frequently associated with a break in the skin known as an open fracture. Because the bone is exposed by the open wound, open tibial fractures are often complicated by infection and failure of bone healing, which can lead to long-lasting disability and in some cases amputation. Intravenous antibiotics administered early after injury are a well-established measure to prevent fracture-related infection (FRI), but their effectiveness is limited by poor blood flow at the fracture site and inability to achieve high local concentrations with systemic administration. Gentamicin applied locally within the open fracture wound is a promising adjunctive measure to reduce the risk of FRI after these injuries, but there are no high-quality clinical trials evaluating its use.

This will be the first randomized trial evaluating locally administered gentamicin to reduce infection in a fracture population. If efficacious, local gentamicin is likely to be a highly cost-effective preventive strategy for FRI and may ultimately be cost saving. Although these findings will originate from a low-income country, results may be generalizable to populations in both high and low-income countries and could therefore significantly reduce the global burden of open fractures.

Eligibility criteria: Inclusion Criteria:

* Age\>18 years old
* Open tibial shaft fracture meeting the following criteria:

  1. Orthopaed Trauma Association (OTA) Type 42
  2. Primarily closable wound
  3. Gustilo-Anderson (GA) Type I, II, or IIIA

Exclusion Criteria:

* Time from injury to presentation \> 48 hours
* Time from injury to surgery \> 7 days
* Aminoglycoside allergy
* GA IIIB or IIIC open fractures
* Bilateral open tibial fractures
* Severe brain (GCS\<12) or spinal cord injury
* Severe vascular injury
* Severe burns (\>10% Total Body Surface Area (TBSA) or \>5% TBSA with full thickness or circumferential injury)
* Pathologic fracture
* History of active limb infection, ipsilaterally
* Unlikely to complete follow-up

Primary outcomes:
measure: Occurrence of fracture-related infection (FRI)
timeFrame: 12 months
Secondary outcomes:
measure: Occurrence of nonunion
timeFrame: 12 months
measure: Occurrence of unplanned fracture-related reoperation
timeFrame: 12 months
measure: Health-related quality-of-life (HRQOL) as measured by EQ-5D-3L (Swahili version)
timeFrame: 12 months
measure: Fracture healing by modified Radiographic Union Scale for Tibial fractures (mRUST score)
timeFrame: 12 months
measure: Clinical fracture healing by Function IndeX for Trauma (FIX-IT)
timeFrame: 12 months
measure: Occurence of FRI Suggestive Criteria
timeFrame: 12 months
Other outcomes:
measure: Adverse events
timeFrame: 12 months
measure: Fold-change in creatinine level
timeFrame: 2 days
Locations:
city: Dar es Salaam
country: Tanzania
facility: Muhimbili Orthopaedic Institute
Study officials:
affiliation: University of California, San Francisco
name: David W Shearer, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Muhimbili Orthopaedic Institute
name: Billy T Haonga, MD
role: PRINCIPAL_INVESTIGATOR
References: