Less Infections for the Diabetic Foot

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Randomized Study Comparing Different Durations of Antibiotic Treatment for Diabetic Foot Infections

Conditions
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Diabetic Foot

Intervention / Treatment
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* Procedure: Surgical debridement (if needed)
* Diagnostic Test: Microbiological sampling
* Procedure: Revascularisation (if needed).
* Device: Off-loading
* Behavioral: Patient's education and instructions
* Procedure: Wound debridement
* Drug: Antibiotic duration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 Diabetes mellitus Diabetic Foot Infections Surgical intervention to remove all necrotic tissue or tenotomy. Osteomyelitis limited to bone contact or cortical lesions in X-ray. Exclusion Criteria: Implanted device. More than 96 hours of systemic antibiotic therapy prior to inclusion Amputation Destructive osteomyelitis Concomitant infections requiring more than 14 days of antibiotic therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two prospected-randomized protocols
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Short antibiotic arm<br>10 days for soft tissue infections 3 weeks for osteomyelitis | Procedure: Surgical debridement (if needed)<br>* Surgical debridement<br>Diagnostic Test: Microbiological sampling<br>* Microbiological sampling<br>Procedure: Revascularisation (if needed).<br>* Revascularisation (if needed).<br>Device: Off-loading<br>* Off-loading by Special shoes<br>Behavioral: Patient's education and instructions<br>* Patient's education and instructions by specialized nurses<br>Procedure: Wound debridement<br>* Regular wound debridement by specialized nurses<br>Drug: Antibiotic duration<br>* Systemic antibiotic duration according to the study arms<br>|
| Active Comparator: Standard antibiotic arm<br>20 days for soft tissue infections 6 weeks for osteomyelitis | Procedure: Surgical debridement (if needed)<br>* Surgical debridement<br>Diagnostic Test: Microbiological sampling<br>* Microbiological sampling<br>Procedure: Revascularisation (if needed).<br>* Revascularisation (if needed).<br>Device: Off-loading<br>* Off-loading by Special shoes<br>Behavioral: Patient's education and instructions<br>* Patient's education and instructions by specialized nurses<br>Procedure: Wound debridement<br>* Regular wound debridement by specialized nurses<br>Drug: Antibiotic duration<br>* Systemic antibiotic duration according to the study arms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Clinical Failure | Visual and dichotomous evaluation regarding the numbers of clinical recurrence/failure | 30-60 days | 

Secondary Outcome Measures

| Outcome Measure | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetic foot infections, antibiotic reduction, osteomyelitis, soft tissue infections