This is a Phase III clinical randomized control trial to investigate differences between patient with an infected nonunion treated by PO vs. IV antibiotics. The study population will be 250 patients, 18 years or older, being treated for infected nonunion after internal fixation of a fracture with a segmental defect less than one centimeter. Patients will be randomly assigned to either the treatment (group 1) PO antibiotics for 6 weeks or the control group (group 2) IV antibiotics for 6 weeks. The primary hypothesis is that the effectiveness of oral antibiotic therapy is equivalent to traditional intravenous antibiotic therapy for the treatment of infected nonunion after fracture internal fixation, when such therapy is combined with appropriate surgical management. Clinical effectiveness will be measured as the primary outcome as the number of secondary re-admissions related to injury and secondary outcomes of treatment failure (re-infection, nonunion, antibiotic complications) within the first one year of follow-up, as defined by specified criteria and determined by a blinded data assessment panel. In addition, treatment compliance, the cost of treatment, the number of surgeries required, the type and incidence of complications, and the duration of hospitalization will be measured.
1. Bone fracture (proximal to and including the tarsal/metatarsal joint (Lisfranc) or proximal to the carpal joints (includes distal radius fractures), excluding pelvis and spine) that has previously undergone fixation and has not healed and requires fixation to be retained or replaced at least until bone union. Fractures that have not healed and require revision fixation are also eligible.
Infection as determined by either
FRI criteria
CDC criteria (without the timeframe) This includes the possibility of culture negative, but determined to be infection by treating surgeon
Patients with a high risk of amputation based on the initial managing physician
Patients undergoing treatment of any other investigational therapy within the month preceding infection treatment or planned within the 12 months following infection treatment
Incarcerated or institutionalized patients
Patients who are unable to return for required follow-up visits and/or medical co-morbidities which preclude treatment with a general anesthetic
Parallel
Standard of Care PO (oral) antibiotics
DrugAn intervention in this study includes randomization of patients with an infected nonunion to PO (oral) antibiotics for up to 6 weeks post hospitalization. The exact type of oral antibiotic will be depended on the patient's infection diagnosis.
Standard of Care Intravenous (IV) antibiotics
DrugAn intervention in this study includes randomization of patients with an infected nonunion to intravenous (IV) antibiotics for up to 6 weeks post hospitalization. The exact type of IV antibiotic will be depended on the patient's infection diagnosis.
Number of patients with a hospital re-admission
Total number of re-admissions after revision fixation over the first 365 days post discharge from the hospitalization for initial surgical treatment of the infected nonunion. Re-admission can be for infection, nonunion, soft tissue revision, line complication, or antibiotic complication.
Number of patients with treatment failure
Treatment Failure will define as patients with the following complications: * Wound problems requiring surgery * Patients that have culture positive recurrence of infection * Progressive radiographic loosening of the implant * Joint erosion due to infection * Infection with a new organism * Adverse reactions to any of the antibiotics * Infection recurrence * Persistent Nonunion
Number of patients with a re-hospitalization for a complication
Re-hospitalization for Complication is defined as: 1. any re-admission to the hospital secondary to the treatment of the deep wound infection associated with the index fracture fixation for a defined set of complications. The list of complications includes: nonunion, amputation, infection, flap failure, , This definition has successfully been used by the core centers in previous published prospective studies and is consistent with the data used to generate the study power estimate. 2. any complication of IV access requiring rehospitalization including, but not limited to line sepsis, DVT in same extremity as IV access, pneumothorax, or line change due to malfunction.
Number of patients with an additional infection
Infection will be assessed either as systemic inflammation or surgical site infection.
Number of patients that experienced amputation
Amputation is defined as surgical procedure to remove part of an extremity due to persistent infection or nonunion on proximal to site on affected extremity.
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Major Extremity Trauma Research Consortium
Lead sponsor
United States Department of Defense
Collaborator
