Four-Week vs Six-Week Antibiotic Therapy in the Management of Nonsurgically Treated Diabetic Foot Osteomyelitis: Protocol for a Multicentric, Single-Blind Randomized Clinical Trial.

backgroundDiabetic foot osteomyelitis (DFO) is a common complication and major cause of morbidity among people with diabetes mellitus. There has been growing acceptance of primarily nonsurgical (conservative) management of DFO based on antibiotics alone. However, the most appropriate duration of antibiotic therapy for DFO remains controversial. Current guidelines recommend antibiotic duration of up to 6 weeks for DFO. Although there has been growing interest in a shorter duration of antibiotic therapy, in absence of sufficient evidence, the extent to which the duration of antibiotic therapy can be shortened remains debatable. Determination of the optimal duration of antibiotic therapy would improve the outcomes of treatment of DFO while limiting side effects.

objectiveThis study aims to determine the rates of remission (primary objective) and adverse events (secondary objective) associated with 4 vs 6 weeks of antibiotic therapy in nonsurgically treated DFO.

methodsIn this single-blind randomized clinical trial, eligible people with DFO who give consent will be randomized to 4 or 6 weeks of antibiotic therapy in a 1:1 ratio. Participants will be treated according to current guidelines. First, an empirical antibiotic therapy to be modified if required according to the results of bone culture will be administered. Additional supportive therapy (wound care, pressure off-loading, and professional care for control of glucose levels and other comorbidities) will be provided as indicated. Participants will be followed up until 6 months after antibiotic discontinuation. Radiographs and magnetic resonance images will be obtained at baseline, and at 6 weeks and after 6 months of discontinuation of antibiotics. Hematologic, renal, and hepatic parameters will be assessed during treatment. DFO remission-defined as a composite of sustained wound healing, absence of local or systemic signs of infection, stabilization or improvement in radiologic signs, absence of recurrence of osteomyelitis at the initial or contiguous site, and absence of requirement of amputation or bone resection-will be prospectively assessed at 6 months after end of antibiotic therapy. The investigator responsible for the outcome assessment will be blinded to participants' group assignment. The sample size was calculated to be 52 participants in each group. The randomized clinical trial will be a noninferiority study. Outcomes will be published as intention-to-treat and per-protocol database.

resultsThis study received sanction of research grant and budget allotment in March 2025. Data collection commenced in December 2025. As of February 2026, a total of 7 participants have been enrolled. The results are expected to be published by the first quarter of 2029.

conclusionsThis study is expected to generate high-quality evidence on the optimum duration of antibiotic therapy in DFO.

trial registrationClinical Trials Registry - India CTRI/2025/02/080469; https://tinyurl.com/2aef5ex7. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/93492.