Topical antibiotic therapy to reduce infection after operative treatment of fractures at high risk of infection: TOBRA-a multicenter randomized controlled trial protocol

Abstract

Introduction: Complex articular fractures of the proximal (plateau) and distal (pilon) tibia carry a substantial risk of deep surgical site infections (SSIs), often resulting in serious complications and hospital readmissions. The TOBRA study is a multicenter, randomized controlled trial designed to determine if the combination of vancomycin plus tobramycin powder is more effective than vancomycin alone in decreasing the risk of deep SSIs after definitive fixation of these high-risk fractures. Methods and analysis: Adults aged 18-80 years with at least one risk factor for infection (eg, open fracture, fasciotomy) are randomized 1:1 to receive either 1 gram of vancomycin alone or 1 gram of vancomycin plus 1.2 grams of tobramycin applied directly into the wound at the time of closure. The primary outcome is a deep SSI requiring surgery within 182 days of fixation, adjudicated by an expert panel blinded to treatment allocation. Secondary outcomes include infection subtypes (gram-negative, culture-negative), wound complications, and adverse drug reactions. The study uses Bayesian Cox regression to evaluate the primary end point, with superiority defined as a posterior probability greater than 0.95. The trial will enroll 1550 participants across sites in the Major Extremity Trauma Research Consortium (METRC). Findings will help guide antibiotic prophylaxis strategies in orthopaedic trauma patients at high risk of infection. Ethics and dissemination: Ethical approval has been granted by the Pearl Institutional Review Board, the Department of Defense Human Research Protections Office, and the local Institutional Review Board at each participating site. Alongside journal publications, dissemination activities include sharing results with participating trial sites and patients and data sharing (upon reasonable request) with researchers.