Infectious Disease · Medical Literature
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.
Abstract
Diabetic 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. This 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. In 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. This 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. This study is expected to generate high-quality evidence on the optimum duration of antibiotic therapy in DFO. Clinical Trials Registry - India CTRI/2025/02/080469; https://tinyurl.com/2aef5ex7. DERR1-10.2196/93492.
Clinical relevance
In adults with diabetic foot osteomyelitis (DFO) managed nonsurgically with antibiotics alone, is a 4-week course of antibiotic therapy noninferior to the standard 6-week course with respect to rates of remission and adverse events? __SNAPSHOT__ {"studyDesign":"Protocol for a multicentric, single-blind, noninferiority randomized controlled trial (trial registration: Clinical Trials Registry – India CTRI/2025/02/080469). Note: This publication describes the study protocol only; no efficacy or safety results are yet available.","setting":"Multiple tertiary academic medical institutions in India, including All India Institute of Medical Sciences (AIIMS) Raipur, Post Graduate Institute of Medical Education and Research (PGIMER) Chandigarh, and Institute of Post Graduate Medical Education and Research (IPGMER) Kolkata.","sampleSize":"Planned n=104 (intervention: 52, control: 52); as of February 2026, 7 participants had been enrolled.","population":"Adults with diabetes mellitus diagnosed with diabetic foot osteomyelitis (DFO) who are candidates for nonsurgical (conservative, antibiotic-only) management and who provide informed consent. Precise inclusion/exclusion criteria are detailed in the full protocol but not fully enumerated in the available abstract.","intervention":"4 weeks of antibiotic therapy for nonsurgically treated DFO, initiated empirically and subsequently guided by culture results per current guidelines.","comparator":"6 weeks of antibiotic therapy for nonsurgically treated DFO (current guideline-recommended standard duration), managed according to the same protocol.","primaryOutcome":"Rate of 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 for amputation or bone resection — assessed prospectively at 6 months after completion of antibiotic therapy.","followUp":"6 months after the end of antibiotic therapy.","fundingSource":"Indian Council of Medical Research (ICMR) government research grant (sanctioned March 2025); peer-reviewed by ICMR."}
Key findings
This publication is a study protocol, not a results paper. No efficacy data, remission rates, adverse event rates, between-group differences, p-values, confidence intervals, or effect sizes are reported. Enrollment commenced in December 2025, and as of February 2026, only 7 of the planned 104 participants had been enrolled. Outcome data will be analyzed and reported on an intention-to-treat and per-protocol basis upon trial completion. No findings regarding the primary or secondary endpoints are available at this time.
Practice implications
This publication establishes only the rationale, design, and methodology of the trial — it does not establish efficacy or safety of 4-week versus 6-week antibiotic therapy for nonsurgically treated DFO. The trial is motivated by the growing acceptance of conservative DFO management and the recognition that current guideline recommendations for up to 6 weeks of antibiotics lack robust comparative evidence for duration. The noninferiority design is methodologically appropriate for this research question. Clinicians should not alter current practice based on this protocol paper alone. The population studied (Indian tertiary-center patients) may differ in comorbidity burden, pathogen profile, antibiotic resistance patterns, and healthcare access from patient populations in other settings, which will limit generalizability. Patients with severe peripheral arterial disease, immunosuppression, or organisms requiring prolonged therapy are likely to be underrepresented or excluded. Results, when available, will need to be interpreted in the context of the noninferiority margin chosen and the definition of remission used, which requires 6-month sustained composite outcomes. Only the abstract was available for this review; full protocol details (eligibility criteria, antibiotic regimens, noninferiority margin) should be consulted in the complete publication. __LIMITATIONS__ This is a protocol publication only — no clinical results, effect sizes, or safety data are reported; the structured summary is necessarily incomplete.,As of February 2026, only 7 of 104 planned participants had been enrolled, raising concerns about feasibility and potential prolonged recruitment timeline.,Single-blind design (outcome assessor blinded, but participants and treating clinicians are not blinded) introduces potential performance and detection bias.,Planned sample size of 52 per arm is modest, and the noninferiority margin is not fully specified in the abstract — an overly generous margin could render the trial clinically uninformative.,Multicentric design across Indian tertiary academic centers may limit generalizability to community-based settings, different healthcare systems, and regions with distinct microbial epidemiology or antibiotic resistance profiles.,The composite remission endpoint assessed at 6 months post-antibiotic therapy is clinically meaningful, but components of the composite may have differing clinical weights; analysis of individual components will be important.,Antibiotic choice and sequencing (empirical then culture-directed) introduce heterogeneity in actual drug exposures between participants, which may confound duration-specific inferences.,The abstract does not specify whether patients with critical limb ischemia, immunosuppression, or MRSA/multidrug-resistant organisms are excluded — these subgroups are at substantially higher failure risk and their representation will affect external validity.,Government funding (ICMR) reduces but does not eliminate risk of institutional bias; long-term post-trial surveillance beyond 6 months is not described. __BOTTOM_LINE_CATEGORY__ not_ready_for_clinical_application __BOTTOM_LINE__ This paper describes only the protocol for an ongoing Indian multicentric noninferiority RCT comparing 4 versus 6 weeks of antibiotics for nonsurgically managed diabetic foot osteomyelitis; no efficacy or safety data are yet available. The trial is scientifically well-motivated and addresses a clinically important and unresolved question, but with only 7 of 104 participants enrolled as of February 2026, results remain years away. Current practice should continue to follow established guideline recommendations of up to 6 weeks of antibiotic therapy for nonsurgically treated DFO until this or similar trials report mature outcome data.