The study design is a randomized, open-label, clinical trial of omadacycline vs Standard of Care (SOC) antibiotics for bone and join infection (BJI) treatment. Study participants will have their BJI regimen chosen by their treating physicians, (typically Infectious Diseases for hardware and prosthetic joint infections, or multidisciplinary Limb Salvage team for diabetic foot infections) prior to enrollment. Then participants will be randomized to an omadacycline-containing regimen versus the a priori chosen SOC regimen. Participants must require between 4 and 12 weeks of therapy for their BJI. The exact duration of therapy will be decided by the participants' treating physician. At 12 weeks, if the treating physician wishes to extend therapy, participants receiving omadacycline will be transitioned to other SOC antibiotics.~The primary endpoint is treatment efficacy 2-weeks after therapy completion. Investigators hypothesize that omadacycline will be non-inferior to SOC antibiotics for BJI treatment. For our primary analysis, investigators will dichotomize outcomes to treatment success and treatment failure. Treatment success will be defined as the lack of definite treatment failure. Treatment failure will be defined using the definition utilized in the OVIVA trial. Specifically, failure will be defined as the presence of at least one clinical criterion (draining sinus tract arising from bone or prosthesis or the presence of frank pus adjacent to bone or prosthesis), microbiologic criterion (phenotypically indistinguishable bacteria isolated from two or more deep-tissue samples or a pathogenic organism from a single closed aspirate or biopsy), or histologic criterion (presence of characteristic inflammatory infiltrate or microorganisms).~For descriptive purposes, failure will be subdivided into definite failure, probable failure, and possible failure. Using definitions from the OVIVA trial, definite evidence of treatment failure will be defined by one or more of the following: a) isolating bacteria from 2 or more samples of bone/peri-prosthetic tissue, where the bacteria isolated from these samples were indistinguishable according to routine laboratory tests, including the antibiogram; b) a pathogenic organism (e.g. Staphylococcus aureus but not Staphylococcus epidermidis) on a single, closed, biopsy of native bone or periprosthetic tissue; c) diagnostic histology on bone/peri-prosthetic tissue; d) a draining sinus tract arising from bone/prosthesis; or e) frank pus adjacent to bone/ prosthesis. If any of these criteria are met, then the category definitive infection will be applied. Where these criteria are not met, the following criteria will be used to determine probable or possible infection: Infection will be categorized as probable, where microbiological sampling had not been undertaken, AND none of the other criteria for definite infection had been fulfilled AND any one of the following are met: a) Radiological or operative findings of periosteal changes suggesting chronic osteomyelitis OR b) Radiological findings suggesting vertebral infection OR c) The development of a discharging wound after an orthopaedic procedure where prosthetic material had been implanted OR d) The presence of deep pus close to but not adjacent to bone/prosthetic joint/orthopedic device OR e) The presence of peri-prosthetic necrotic bone OR f) Rapid loosening of a joint prosthesis/orthopedic device (i.e. leading to localized pain in less than 3 months since implantation) in the absence of a mechanical explanation for rapid loosening. Infection will be categorized as possible where microbiological sampling had been undertaken with negative results (according to criteria described above for definite infection) AND other criteria for definite infection were not fulfilled AND in addition one or more of the criteria listed a) to f) above is met.~Secondary endpoints include long-term efficacy, safety, tolerability, medication adherence, early discontinuation of the randomly assigned treatment strategy, and probable or possible treatment failure. Investigators will measure long-term efficacy by performing a phone survey 3 months after antibiotic completion. Definition of treatment efficacy will be same as primary endpoint, which is specified above. Unplanned surgical procedures prompted by inadequate infection control will be categorized as treatment failure. Recurrence of signs or symptoms of BJIs after resolution will be considered a long-term treatment failure.~Once enrolled, participants will be followed via in-person clinic visits at the following intervals: weeks 0, 2, 4, 8, and 12. A final in-person visit will occur 2 weeks post-treatment completion. A phone survey will occur 3 months post-treatment completion. Participants in the SOC group will follow the same schedule.~Oral once-daily dosing options for S. aureus and Coagulase negative Staphylococcus are essentially non-existent. Thus, omadacycline possesses a novel and advantageous option for BJI treatment. Its convenient dosing regimen will almost certainly be associated with improved adherence, and higher adherence may, in turn, improve clinical outcome. Investigators hypothesize that omadacycline will be a well-tolerated and efficacious oral antibiotic for BJIs and will be associated with improved adherence compared with standard of care oral antibiotics. Investigators believe omadacycline addresses the unmet need for an oral antibiotic that is well-tolerated and efficacious for use as a prolonged therapy for BJIs. To this aim, investigators will perform a randomized, open-label clinical trial of omadacycline to SOC antibiotics for BJIs.
The study design is a randomized, open-label, clinical trial of omadacycline vs Standard of Care (SOC) antibiotics for bone and join infection (BJI) treatment. Study participants will have their BJI regimen chosen by their treating physicians, (typically Infectious Diseases for hardware and prosthetic joint infections, or multidisciplinary Limb Salvage team for diabetic foot infections) prior to enrollment. Then participants will be randomized to an omadacycline-containing regimen versus the a priori chosen SOC regimen. Participants must require between 4 and 12 weeks of therapy for their BJI. The exact duration of therapy will be decided by the participants' treating physician. At 12 weeks, if the treating physician wishes to extend therapy, participants receiving omadacycline will be transitioned to other SOC antibiotics.~Once enrolled, participants will be followed via in-person clinic visits at the following intervals: weeks 0, 2, 4, 8, and 12. A final in-person visit will occur 2 weeks post-treatment completion. A phone survey will occur 3 months post-treatment completion. Participants in the SOC group will follow the same schedule.~Oral once-daily dosing options for S. aureus and Coagulase negative Staphylococcus are essentially non-existent. Thus, omadacycline possesses a novel and advantageous option for BJI treatment. Its convenient dosing regimen will almost certainly be associated with improved adherence, and higher adherence may, in turn, improve clinical outcome. Investigators hypothesize that omadacycline will be a well-tolerated and efficacious oral antibiotic for BJIs and will be associated with improved adherence compared with standard of care oral antibiotics. Investigators believe omadacycline addresses the unmet need for an oral antibiotic that is well-tolerated and efficacious for use as a prolonged therapy for BJIs. To this aim, investigators will perform a randomized, open-label clinical trial of omadacycline to SOC antibiotics for BJIs.