Pilot RCT Local Gentamicin for Open Tibial Fractures in Tanzania

A Pilot Masked, Randomized Controlled Trial Evaluating Locally-applied Gentamicin Versus Saline in Open Tibia Fractures

Local application of antibiotics directly to the traumatic wound is a promising strategy for the prevention of infection after open tibia fractures, which are a significant source of disease burden globally, particularly in low-income countries. This pilot study aims to assess feasibility of a randomized controlled trial 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.

This pilot study is being conducted in Dar es Salaam, Tanzania to assess the feasibility of a masked, placebo-controlled, randomized trial to compare local gentamicin injection to saline injection in open tibial shaft fractures. The study will enroll patients within 1 week of injury. The active or placebo agent will be administered during the initial surgical debridement based on a web-based randomization tool. Patients will be followed for 1 year after surgery to assess for the occurrence of fracture-related infection (FRI), a consensus definition of infection after open fracture or insertion of internal fixation to treat fracture. Additional clinical and economic endpoints will also be measured.

Depending on the outcome of the feasibility study, we may undertake a definitive trial to test the effectiveness of local gentamicin to prevent FRI. If proven effective, local gentamicin would impact the clinical care of open fracture patients both in Tanzania and likely in high-income settings as well. These data will also deepen the understanding of the clinical and economic impact of FRI in open fracture populations.

Inclusion Criteria:

1. Male or female patients age 18 or older

2. Diagnosis of an acute open tibial shaft fracture meeting the following criteria:

   1. AO/OTA Type 42
   2. Primarily closable wound
   3. Type I, II, or IIIA Gustilo- Anderson (GA) Classification

Exclusion Criteria:

1. Time from injury to presentation > 48 hours
2. Time from injury to surgery >7 days
3. History of Aminoglycoside allergy
4. GA IIIB or IIIC open fractures
5. Bilateral open tibial fractures
6. Severe brain (GCS<12) or spinal cord injury
7. Severe vascular injury
8. Sustained severe burns (>10% total body surface area (TBSA) or >5% TBSA with full thickness or circumferential injury)
9. Pathologic fracture
10. History of active limb infection, ipsilaterally