Pilot RCT Local Gentamicin for Open Tibial Fractures in Tanzania

The number of participants enrolled in the clinical trial per month will be measured to assess feasibility of the definitive clinical trial.

The percentage of patients completing 1 year follow up relative to the total number of participants

The primary outcome for the definitive trial is occurrence of fracture-related infection (FRI), a binary variable. Any of the four following diagnostic criteria are confirmatory for FRI:

• fistula, sinus or wound breakdown
• purulent drainage from the wound or presence of pus during surgery
• phenotypically indistinguishable pathogens identified by culture from at least two separate deep tissue/implant specimens
• presence of microorganisms in deep tissue taken during an operative intervention, as seen on histopathological examination.

All primary events will be reviewed by a masked adjudication committee comprised of 3 non-treating fellowship-trained orthopaedic trauma surgeons.

EuroQol-5 Dimensions (EQ-5D) measures general health status in five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The raw score will be translated to a utility score ranging from 0 (death or no health) to 1 (perfect health) on a continuous scale using health-state valuations from Zimbabwe.

Radiographic healing as measured by the modified Radiographic Union Scale for Tibial fractures (mRUST). mRUST scores each cortex on an AP and lateral radiograph from a score of 1 (no callus) to 4 (remodeled, fracture not visible). Thus, mRUST ranges from 4 (worst healing score) to 16 (best healing score).

Clinical healing of the fracture will be assessed using the Function index for trauma (FIX-IT) score, which evaluates weight bearing and pain in patients with lower extremity fractures. The FIX-IT score is a clinical outcomes assessment measure ranging from 0 to 12 points in two domains: the ability to bear weight (maximum 6 points) and pain at the fracture site (maximum 6 points). The maximum score of 12 indicates the highest level of function.

Nonunion is a binary variable defined by the following criteria:

• any unplanned reoperation for promotion of bone healing; OR
• mRUST<=10 AND either: FIX-IT score <=11 at 12-month follow-up OR recommendation by treating surgeon for nonunion repair surgery

This binary variable includes reoperation for infection, wound healing, or fracture union, and excludes the removal of implants for prominence/irritation.

Direct medical costs of treatment (continuous), including medications, personnel, and supplies will be measured for both the intervention and control groups.

Indirect (time) costs, such as lost productivity, will be measured using the Work Productivity and Activity Impairment questionaire (WPAI)

C-Reactive protein (CRP) is a known inflammatory marker which may show signs of early infection. The value will be measured in all patients and reported at 6 weeks post-surgery.

For cases undergoing reoperation for which deep tissue cultures are taken, the frequency of each bacterial species will be reported as a percentage of total FRI for both treatment groups.