Real-World Efficacy and Safety Analysis of Omadacycline for the Treatment of Diabetic Foot Infections and Acute Osteomyelitis

Study Overview
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Brief Summary
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This will be a prospective, open-label, two-center study to assess the safety of omadacycline use in the treatment of hospitalized subjects with moderate to severe DFI with or without Acute osteomyelitis (AOM) who are at a high risk for development of CDI, AKI, and/or resistant pathogens compared to retrospective controls. Prospective enrollment will be continued until the sample size is achieved up to one year from start date (October 2020). Secondary to slower than anticipated enrollment due to the COVID-19 pandemic and initial exclusion of AOM, following protocol amendment, patient enrollment will be continued until the sample size is achieved up to 18 months from amendment approval (anticipate April 2022 - October 2023). A historical matched case cohort (standard of care) at the two hospitals based on ICD10 codes associated with DFI [E11.(621, 622), E10.(621, 622); L97.(509, 521, 522, 523, 524, 529)], including subjects with AOM [M86.(08-09, 10, 16-19, 8X0, 8X7-8X9, 9) will be utilized for comparison.

Detailed Description
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This is a year-long study with planned enrollment of 57 patients (in addition to 114 historical control patients) evaluating the use of omadacycline for treatment of diabetic foot infections (DFI). Omadacycline (Nuzyra®) is a FDA approved antibiotic for skin and skin structure infection and community-acquired pneumonia. This study is considered to be investigational because data is being collected on the use of Omadacycline for the treatment of DFI with or without AOM.

Official Title
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Real-World Efficacy and Safety Analysis of Omadacycline for the Treatment of Diabetic Foot Infections and Acute Osteomyelitis

Conditions
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Diabetic Foot Infection

Intervention / Treatment
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* Drug: Omadacycline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female and male subjects will be eligible for inclusion if hospitalized, 18 years or older, diagnosed with type 1 or 2 diabetes, and have DFI with the additional clinical criteria as specified below: Acute infection or worsening without systemic antimicrobials within the previous 14 days At least one full or partial thickness-infected ulcer at or below the ankle AND Purulent drainage OR Two of the following: Erythema Local edema Fluctuance Induration Increased local warmth Fever No systemic antimicrobials with current hospital admission for more than 48 hours prior to enrollment Inclusion will be based on Empiric coverage based on organisms suspected to be caused by susceptible bacteria, if no culture identifies a specific organism; or Confirmed susceptibility to omadacycline against any organism identified. Any subject in which a pathogen resistant to omadacycline is identified will be excluded from the study and antibiotics will be changed based on physician discretion. First episodes of AOM at qualifying site of infection will be eligible for inclusion with any of the following criteria confirming the diagnosis: Imaging (X-ray or MRI) confirmation of acute osteomyelitis Pathology (bone biopsy/culture) Not currently enrolled in any other clinical trial Provides informed consent Likely to be compliant with all study-related procedures and visits Exclusion Criteria: Age less than 18 years Pregnant women Chronic osteomyelitis Osteomyelitis of the same site previously treated with antibiotics Documented presence of osteomyelitis more than 2 weeks prior to index admission Necrotic or dead bone identified by pathology Unclear chronicity of infection (if unable to determine acute osteomyelitis) Has any gangrenous ulcers or necrotizing fasciitis Has a pathogen known to be resistant to omadacycline Administration of additional systemic antibiotics in combination with omadacycline, not including topical routes or oral vancomycin/fidaxomicin given their local activity within the GI tract Contraindication or hypersensitivity to omadacycline/tetracyclines Unwilling or unable to participate in study-related procedures or visits

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Retrospective Cohort<br>A historical matched case cohort | |
| Prospective Cohort<br>Subjects will be screened daily via review of the EMR reports of inpatient admissions. Those receiving antibiotics with a notated source of skin/soft tissue infection or OM will be further reviewed to determine if the source of infection is a DFI with or without suspected or confirmed Acute osteomyelitis. | Drug: Omadacycline<br>* Omadacycline monotgherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AKI based on RIFLE criteria | Risk, injury, failure, loss and ESRD | Sept 2020 - Aug 2021 | 
| Clostridioides difficile Infection | Frequency of Clostridioides difficile Infections while taking Omadacycline compared to other antibiotics | Sept 2020 - Aug 2021 |