Study Protocol: Optimization of the surgical and medical management of diabetic foot infections

Abstract

Background: Few studies address the appropriate duration of antibiotic therapy for diabetic foot infections (DFI); with or without amputation. We perform two randomized clinical trials (RCT) to reduce the antibiotic use and associated adverse events in DFI.Methods: We hypothesize that shorter durations of post-debridement systemic antibiotic therapy are non-inferior (10% margin, 80% power, ɑ 5%) to existing (long) durations and perform two unblinded RCTs with a total of 400 DFI episodes (randomization 1:1) from 2019 to 2022. The primary outcome for both RCT is "remission of infection" after a minimal follow-up of two months. The 1 st RCT allocates the amputations in two arms of 50 patients each: 1 vs. 3 weeks of antibiotic therapy for residual osteomyelitis (positive microbiological samples of the residual bone stump); or 1 vs. 4 days for remaining soft tissue infection. The 2 nd RCT randomizes the conservative approach in two arms with 50 patients each: 10 vs. 20 days of antibiotic therapy for soft tissue infections; and 3 vs. 6 weeks for osteomyelitis. All participants have professional wound debridement, adequate off-loading, angiology evaluation, and a concomitant surgical, re-educational, internist and infectiology care.During the surgeries, we collect tissues for BioBanking and future laboratory studies.Discussion: Both parellel RCT will enable to prescribe less antibiotics for DFI; for a conservative therapy and after amputation. Trial registration: ClinicalTrial.gov NCT04081792. Registered on 4 th September 2019. Protocol version : 2 (15 th July 2019) Study settingThe Balgrist University Hospital in Zurich is a tertiary referral center for DFI and amputations (emergency and elective consultations with a 24-hour service) and affiliated to the University of Zurich. Regarding DFIs, it resumes a multidisciplinary team composed of four diabetic foot surgeons, three internist physicians, a hospital pharmacist, five specialized wound nurses, musculoskeletal expert radiologists, a diabetes nurse, three nutritionists, a shoemaker, a prosthesis specialist, and up to four infectious diseases physicians who are specialized in orthopedic infections. Moreover, this team is supported by an in-house company for orthopedic footwear (Balgrist Tec) and individual adaptations of off-loading devices, a re-education unit, physical therapy, a research campus (Balgrist