Less Infections for the Diabetic Foot

• ClinicalTrials.gov Identifier: NCT03615807
• Recruitment Status: Completed
• First Posted: August 6, 2018
• Results First Posted: June 1, 2020
• Last Update Posted: June 9, 2020
• Sponsor: University Hospital, Geneva
• Information provided by (Responsible Party): Ilker Uckay, University Hospital, Geneva

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Diabetic Foot	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	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 182 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Two prospected-randomized protocols
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Study Comparing Different Durations of Antibiotic Treatment for Diabetic Foot Infections
• Actual Study Start Date: February 16, 2017
• Actual Primary Completion Date: February 29, 2020
• Actual Study Completion Date: March 31, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Experiencing Clinical Failure [ Time Frame: 30-60 days ]
   Visual and dichotomous evaluation regarding the numbers of clinical recurrence/failure

Secondary Outcome Measures :

1. Number of Participants Experiencing Adverse Events Related to the Antibiotic Therapy [ Time Frame: 30-60 days ]
   Adverse events related to the antibiotic therapy.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥ 18
2. Diabetes mellitus
3. Diabetic Foot Infections
4. Surgical intervention to remove all necrotic tissue or tenotomy.
5. Osteomyelitis limited to bone contact or cortical lesions in X-ray.

Exclusion Criteria:

1. Implanted device.
2. More than 96 hours of systemic antibiotic therapy prior to inclusion
3. Amputation
4. Destructive osteomyelitis
5. Concomitant infections requiring more than 14 days of antibiotic therapy.

Contacts and Locations

Locations

Switzerland

Geneva University Hospitals

Geneva, Switzerland, 1211

Sponsors and Collaborators

University Hospital, Geneva

Investigators

• Principal Investigator: Ilker Uçkay, MD; University Hospital, Geneva

  Study Documents (Full-Text)

Documents provided by Ilker Uckay, University Hospital, Geneva:

Study Protocol and Statistical Analysis Plan  [PDF] July 2, 2016

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Ilker Uckay, Prof. Dr. med Ilker Uçkay, University Hospital, Geneva
• ClinicalTrials.gov Identifier: NCT03615807
• Other Study ID Numbers: n° 2016-01008
• First Posted: August 6, 2018
• Results First Posted: June 1, 2020
• Last Update Posted: June 9, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ilker Uckay, University Hospital, Geneva:

diabetic foot infections; antibiotic reduction; osteomyelitis; soft tissue infections

Additional relevant MeSH terms:

Infections; Diabetic Foot; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies; Anti-Bacterial Agents; Anti-Infective Agents