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

Tracking Information

• First Submitted Date: January 16, 2017
• First Posted Date: August 6, 2018
• Results First Submitted Date: April 8, 2020
• Results First Posted Date: June 1, 2020
• Last Update Posted Date: June 9, 2020
• Actual Study Start Date: February 16, 2017
• Actual Primary Completion Date: February 29, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 2, 2020)

Number of Participants Experiencing Clinical Failure [ Time Frame: 30-60 days ]

Visual and dichotomous evaluation regarding the numbers of clinical recurrence/failure

Original Primary Outcome Measures (submitted: July 30, 2018)

• Clinical evaluation [ Time Frame: 30-60 days ]
  Visual and dichotomous evaluation regarding the presence or absence of pus
• Standard x-rays [ Time Frame: 30-60 days ]
  If clinically needed, standard X- rax to see if new radiological bone lesions
• Wound Score [ Time Frame: 30-60 days ]
  A self-made wound score (scale 4-30 points). The scale measures wound depth, undermining of the wound bords, wound contamination on visual Basis and wound redness on visual basis. Each positive item has a point. The Score is the sum of the individual points.

Current Secondary Outcome Measures (submitted: June 2, 2020)

Number of Participants Experiencing Adverse Events Related to the Antibiotic Therapy [ Time Frame: 30-60 days ]

Adverse events related to the antibiotic therapy.

Original Secondary Outcome Measures (submitted: July 30, 2018)

• Adverse Events of prescribed antibiotics [ Time Frame: 30-60 days ]
  Clinical and anamnestic adverse events related to the antibiotic therapy.
• Presence of persistent pain [ Time Frame: 30-60 days ]
  Questionnaire (Likert scale 0-10 points) regarding the presence or absence of pain
• Presence of calor [ Time Frame: 30-60 days ]
  Visual and dichotomous evaluation regarding the presence of heat upon touching the formerly infected diabetic foot

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Less Infections for the Diabetic Foot
• Official Title: Randomized Study Comparing Different Durations of Antibiotic Treatment for Diabetic Foot Infections

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.

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 Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Two prospected-randomized protocols

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Diabetic Foot

Intervention

• 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

Study Arms

• Experimental: Short antibiotic arm
  10 days for soft tissue infections 3 weeks for osteomyelitis
  Interventions:

  • 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
• Active Comparator: Standard antibiotic arm
  20 days for soft tissue infections 6 weeks for osteomyelitis
  Interventions:

  • 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

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 16, 2020): 182
• Original Estimated Enrollment (submitted: July 30, 2018): 150
• Actual Study Completion Date: March 31, 2020
• Actual Primary Completion Date: February 29, 2020 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT03615807
• Other Study ID Numbers: n° 2016-01008
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ilker Uckay, University Hospital, Geneva
• Original Responsible Party: Ilker Uckay, University Hospital, Geneva, Attending, Docent Dr.med Ilker Uçkay
• Current Study Sponsor: University Hospital, Geneva
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: University Hospital, Geneva
• Verification Date: June 2020