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

Diabetic Foot Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04714411
• Other study ID #: 014.PHA.2020.A
• Status: Recruiting
• Start date: November 5, 2020
• Est. completion date: August 18, 2024

Study information

• Verified date: July 2023
• Source: Methodist Health System
• Contact: Crystee Cooper, DHEd
• Phone: 214-947-1281
• Email: ClinicalResearch[@]mhd.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: August 18, 2024
• Est. primary completion date: August 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Diabetic Foot
• Diabetic Foot Infection
• Infections
• Osteomyelitis

Intervention

Drug:
• Omadacycline
Omadacycline monotgherapy

Locations

Country	Name	City	State
United States	Methodist Charlton Medical Center	Dallas	Texas
United States	Methodist Dallas Medical Center	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Methodist Health System

Country where clinical trial is conducted

United States, 

References & Publications (7)

Johnson MJ, Shumway N, Bivins M, Bessesen MT. Outcomes of Limb-Sparing Surgery for Osteomyelitis in the Diabetic Foot: Importance of the Histopathologic Margin. Open Forum Infect Dis. 2019 Sep 10;6(10):ofz382. doi: 10.1093/ofid/ofz382. eCollection 2019 Oct. — View Citation

Lazaro Martinez JL, Garcia Alvarez Y, Tardaguila-Garcia A, Garcia Morales E. Optimal management of diabetic foot osteomyelitis: challenges and solutions. Diabetes Metab Syndr Obes. 2019 Jun 21;12:947-959. doi: 10.2147/DMSO.S181198. eCollection 2019. — View Citation

National Center for Health Statistics (US). Health, United States, 2016: With Chartbook on Long-term Trends in Health. Hyattsville (MD): National Center for Health Statistics (US); 2017 May. Report No.: 2017-1232. Available from http://www.ncbi.nlm.nih.gov/books/NBK453378/ — View Citation

Prompers L, Huijberts M, Apelqvist J, Jude E, Piaggesi A, Bakker K, Edmonds M, Holstein P, Jirkovska A, Mauricio D, Tennvall GR, Reike H, Spraul M, Uccioli L, Urbancic V, Van Acker K, Van Baal J, Van Merode F, Schaper N. Optimal organization of health care in diabetic foot disease: introduction to the Eurodiale study. Int J Low Extrem Wounds. 2007 Mar;6(1):11-7. doi: 10.1177/1534734606297245. — View Citation

Rice JB, Desai U, Cummings AK, Birnbaum HG, Skornicki M, Parsons NB. Burden of diabetic foot ulcers for medicare and private insurers. Diabetes Care. 2014;37(3):651-8. doi: 10.2337/dc13-2176. Epub 2013 Nov 1. Erratum In: Diabetes Care. 2014 Sep;37(9):2660. — View Citation

Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005 Jan 12;293(2):217-28. doi: 10.1001/jama.293.2.217. — View Citation

Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004 May;27(5):1047-53. doi: 10.2337/diacare.27.5.1047. — View Citation

Outcome

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