Optimization of the antibiotic management of diabetic foot infections - Protocol for two randomized controlled trials

Abstract Background: Few studies address the appropriate duration of antibiotic therapy for diabetic foot infections (DFI); with or without amputation. We will 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 we will 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 secondary outcomes for both RCT are the incidence of adverse events and the overall treatment costs. The First RCT will allocate the total therapeutic 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 Second RCT will randomize the conservative approach (only surgical debridement without in toto amputation) 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 will have professional wound debridement, adequate off-loading, angiology evaluation, and a concomitant surgical, re-educational, podiatric, internist and infectiology care. During the surgeries, we will collect tissues for BioBanking and future laboratory studies. Discussion: Both parellel RCTs will repond to frequent questions regarding the duration of antibiotic use in the both major subsets of DFIs, to assure the quality of care, and to avoid unnecessary excesses in terms of surgery and antibiotic use. Trial registration: ClinicalTrial.gov NCT04081792. Registered on 4th September 2019. Protocol version: 2 (15th July 2019)