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This is a randomized, unblinded, single-centre study. After eventual surgical debridement (not amputation), patients will be randomized to receive 1 of 2 targeted antibiotic regimens, in the ratio 1:1.
For diabetic toe osteomyelitis, the patients will be randomized between a 3 and a 6 week's arm, for soft tissue infections between 10 and 20 days. The final assessments used in the primary efficacy analysis will be obtained at the test-of-cure (TOC) visit approximately 60 days after treatment is stopped.
Diabetic foot infections (DFI) are frequent and are associated with a high burden of morbidity, costs, recurrence risk or new episodes of infections. About two-third of recurrent DFI may reveal other microorganisms than in the previous period, suggesting new episodes of infection due to the underlying problem, and/or selection by prior antimicrobial therapy. Osteomyelitis in the diabetic toe is almost always established by contiguous spread of infection from a chronic ulcer. It occurs in up to 15% of patients with a diabetic foot ulcer and about 20% of all DFI (and over half of severe infections) involve bone at presentation. The severity of a diabetic foot infection is based on the local and systemic signs and symptoms of infection and has been categorically defined in the Infectious Disease Society of America guidelines for the "Diagnosis and Treatment of Diabetic Foot Infections" (IDSA guidelines).
Knowing the potential for poor outcomes, many clinicians have tended to treat DFIs with a long duration of antibiotic therapy, with many side effects, development and spreading of antibiotic resistance, and associated costs. Data from recent comparative trials has shown that 1-2 weeks is sufficient for most soft tissue infections, and 4 to 6 weeks appears adequate in those with (unresected) infected bone. Retrospective reviews over the past two decades have demonstrated that about two-thirds of selected patients with diabetic foot osteomyelitis can achieve remission with antibiotic therapy alone (i.e., without bone resection). One recent randomized trial found that treatment with only antibiotic therapy (given for 90 days) gave similar clinical outcomes to treatment with conservative surgery (removal only of the infected bone) along with just a short course of antibiotic therapy. Another randomized trial compared a 6-week against 12-week course of antibiotic therapy, without concomitant surgery, for diabetic foot osteomyelitis and also found similar outcomes.
Likewise, the optimal antibiotic duration for any skin and soft tissue infection is unknown. According to some databases of University of Geneva Hospitals, among 378 skin and soft tissue infections in 346, overall cure was achieved in 330 episodes (87%) after a median antibiotic administration of 15 days. In multivariate Cox regression analysis, duration of antibiotic therapy (HR 1.0, 95%CI 0.96-1.02) did not influence treatment failure among patients with positive MRSA carriage.
Our study intends to optimize the duration of antibiotic therapy in DFI; for skin and soft tissue infections as well as for diabetic toe osteomyelitis that is not amputated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Short antibiotic arm | Experimental | 10 days for soft tissue infections 3 weeks for osteomyelitis |
|
| Standard antibiotic arm | Active Comparator | 20 days for soft tissue infections 6 weeks for osteomyelitis |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Surgical debridement (if needed) | Procedure | Surgical debridement |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Experiencing Clinical Failure | Visual and dichotomous evaluation regarding the numbers of clinical recurrence/failure | 30-60 days |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Experiencing Adverse Events Related to the Antibiotic Therapy | Adverse events related to the antibiotic therapy. | 30-60 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ilker Uçkay, MD | University Hospital, Geneva | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Geneva University Hospitals | Geneva | 1211 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25805867 | Result | Tone A, Nguyen S, Devemy F, Topolinski H, Valette M, Cazaubiel M, Fayard A, Beltrand E, Lemaire C, Senneville E. Six-week versus twelve-week antibiotic therapy for nonsurgically treated diabetic foot osteomyelitis: a multicenter open-label controlled randomized study. Diabetes Care 2015;38:302-307. Diabetes Care. 2015 Apr;38(4):735. doi: 10.2337/dc15-er04b. No abstract available. | |
| 35623048 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Short Antibiotic Arm | 10 days for soft tissue infections 3 weeks for osteomyelitis Surgical debridement (if needed): Surgical debridement Microbiological sampling: Microbiological sampling Revascularisation (if needed).: Revascularisation (if needed). Off-loading: Off-loading by Special shoes Patient's education and instructions: Patient's education and instructions by specialized nurses Wound debridement: Regular wound debridement by specialized nurses Antibiotic duration: Systemic antibiotic duration according to the study arms |
| FG001 | Standard Antibiotic Arm | 20 days for soft tissue infections 6 weeks for osteomyelitis Surgical debridement (if needed): Surgical debridement Microbiological sampling: Microbiological sampling Revascularisation (if needed).: Revascularisation (if needed). Off-loading: Off-loading by Special shoes Patient's education and instructions: Patient's education and instructions by specialized nurses Wound debridement: Regular wound debridement by specialized nurses Antibiotic duration: Systemic antibiotic duration according to the study arms |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Diabetic foot infections requiring tretement
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| ID | Title | Description |
|---|---|---|
| BG000 | Short Antibiotic Arm | 10 days for soft tissue infections 3 weeks for osteomyelitis Surgical debridement (if needed): Surgical debridement Microbiological sampling: Microbiological sampling Revascularisation (if needed).: Revascularisation (if needed). Off-loading: Off-loading by Special shoes Patient's education and instructions: Patient's education and instructions by specialized nurses Wound debridement: Regular wound debridement by specialized nurses Antibiotic duration: Systemic antibiotic duration according to the study arms |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Experiencing Clinical Failure | Visual and dichotomous evaluation regarding the numbers of clinical recurrence/failure | Posted | Number | Participants | 30-60 days |
|
|
The adverse events were collected during the first two months of therapy.
Adverse Events Definition: Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Short Antibiotic Arm | 10 days antibiotic for soft tissue infections 3 weeks antibiotic for osteomyelitis |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Progressive ischemia leading to necrosis and amputation | General disorders | Systematic Assessment | Progressive ischemia leading to necrosis and amputation |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cutaneous rash | General disorders | Systematic Assessment | Cutaneous rash |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Ilker UCKAY | Balgrist University Hospital | +41 44 386 37 05 | ilker.uckay@balgrist.ch |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 2, 2016 | May 15, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D017719 | Diabetic Foot |
| D010019 | Osteomyelitis |
| D018461 | Soft Tissue Infections |
| ID | Term |
|---|---|
| D003925 | Diabetic Angiopathies |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D016523 | Foot Ulcer |
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Two prospected-randomized protocols
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| Microbiological sampling | Diagnostic Test | Microbiological sampling |
|
| Revascularisation (if needed). | Procedure | Revascularisation (if needed). |
|
| Off-loading | Device | Off-loading by Special shoes |
|
| Patient's education and instructions | Behavioral | Patient's education and instructions by specialized nurses |
|
| Wound debridement | Procedure | Regular wound debridement by specialized nurses |
|
| Antibiotic duration | Drug | Systemic antibiotic duration according to the study arms |
|
| Derived |
| Pham TT, Gariani K, Richard JC, Kressmann B, Jornayvaz FR, Philippe J, Lipsky BA, Uckay I. Moderate to Severe Soft Tissue Diabetic Foot Infections: A Randomized, Controlled, Pilot Trial of Post-debridement Antibiotic Treatment for 10 versus 20 days. Ann Surg. 2022 Aug 1;276(2):233-238. doi: 10.1097/SLA.0000000000005205. Epub 2021 Sep 15. |
| 33242083 | Derived | Gariani K, Pham TT, Kressmann B, Jornayvaz FR, Gastaldi G, Stafylakis D, Philippe J, Lipsky BA, Uckay L. Three Weeks Versus Six Weeks of Antibiotic Therapy for Diabetic Foot Osteomyelitis: A Prospective, Randomized, Noninferiority Pilot Trial. Clin Infect Dis. 2021 Oct 5;73(7):e1539-e1545. doi: 10.1093/cid/ciaa1758. |
| BG001 | Standard Antibiotic Arm | 20 days for soft tissue infections 6 weeks for osteomyelitis Surgical debridement (if needed): Surgical debridement Microbiological sampling: Microbiological sampling Revascularisation (if needed).: Revascularisation (if needed). Off-loading: Off-loading by Special shoes Patient's education and instructions: Patient's education and instructions by specialized nurses Wound debridement: Regular wound debridement by specialized nurses Antibiotic duration: Systemic antibiotic duration according to the study arms |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Participants |
|
|
| Secondary | Number of Participants Experiencing Adverse Events Related to the Antibiotic Therapy | Adverse events related to the antibiotic therapy. | Posted | Number | Participants | 30-60 days |
|
|
|
| 0 |
| 79 |
| 5 |
| 79 |
| 5 |
| 79 |
| EG001 | Long Antibiotic Arm | 20 days antibiotic for soft tissue infections 6 weeks antibiotic for osteomyelitis | 0 | 80 | 6 | 80 | 6 | 80 |
|
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| D007871 |
| Leg Ulcer |
| D012883 | Skin Ulcer |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D048909 | Diabetes Complications |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| D003929 | Diabetic Neuropathies |
| D001850 | Bone Diseases, Infectious |
| D007239 | Infections |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |