A Phase 4 interventional study of Intraosseous Vancomycin and Intravenous Vancomycin in Diabetic Foot Disease, Diabetic Foot Infection and Diabetic Amputation Foot Wound, sponsored by Başakşehir Çam & Sakura City Hospital. Completed at 1 site in Turkey (Türkiye). Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-10.
Sponsored by Başakşehir Çam & Sakura City Hospital · Phase 4, Interventional, and Prevention
This randomized clinical trial compared two routes of vancomycin administration in patients undergoing below-knee amputation for ischemic diabetic foot infection. Patients with diabetic foot infection and impaired lower-extremity circulation may have reduced delivery of intravenously administered antibiotics to the amputation stump. Intraosseous administration may increase local antibiotic exposure at the surgical site while reducing systemic exposure.
Participants were randomly assigned to receive either intraosseous vancomycin or intravenous vancomycin before skin incision. The study evaluated vancomycin concentrations in amputation stump subcutaneous tissue, simultaneous serum vancomycin concentrations, tissue-to-serum concentration ratios, inflammatory marker trajectories, early wound outcomes, pain scores, drain output, reintervention, mortality, renal safety, and systemic adverse events through postoperative follow-up.
Patients with diabetic foot infection and distal ischemia scheduled for below-knee amputation were evaluated by a multidisciplinary diabetic foot council. Eligible patients were randomized in a 1:1 ratio to receive either intraosseous or intravenous vancomycin before skin incision.
In the intraosseous group, 500 mg of vancomycin diluted in 100 mL of normal saline was administered into the proximal tibial metaphysis using a sterile intraosseous vascular access system immediately before skin incision. In the intravenous group, 500 mg of vancomycin was administered intravenously at the same preincision time point. No tourniquet was used.
During surgery, a subcutaneous soft-tissue sample was obtained from the planned amputation stump region, and a simultaneous venous serum sample was collected. Vancomycin concentrations were measured in both samples. The primary pharmacokinetic outcomes were stump subcutaneous soft-tissue vancomycin concentration, serum vancomycin concentration, tissue-to-serum concentration ratio.
Secondary outcomes included postoperative trajectories of white blood cell count, C-reactive protein, procalcitonin, and interleukin-6; early postoperative pain scores; total drain output during the first 24 hours; early wound-healing outcomes assessed using ASEPSIS scores; surgical reintervention; mortality; renal safety outcomes based on serum creatinine; and systemic adverse events including vancomycin infusion reaction, allergic reaction, symptomatic deep vein thrombosis, and pulmonary embolism.
Clarification of Registry Updates
After the original prospective registration of this study, the ClinicalTrials.gov record underwent formatting and clarification updates during PRS review. These updates were made to improve clarity, grammar, readability, units of measurement, time frames, and separation of outcome-measure entries that included more than one assessment or different units of measurement. These updates were not intended to introduce new endpoints after study initiation.
Although some safety variables were described in the original study description or clarified in the registry before the definitive analysis of study results, not all of them had been entered as formal Outcome Measures in the original registration. Therefore, renal function measures, reoperation, mortality, and systemic adverse events are reported in the manuscript as postoperative observations rather than as additional prespecified endpoints.
1,054 studies on the registry are indexed under Diabetic Foot; 222 are open to participants now.
This study's enrollment of 40 is below the median of 60 across 826 interventional studies indexed under Diabetic Foot.
Browse Diabetic Foot studies →Başakşehir Çam & Sakura City Hospital is the lead sponsor of 105 studies on the registry; 36 are open to participants now.
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Exclusion Criteria:
Participants received 500 mg of vancomycin diluted in 100 mL of 0.9% normal saline via intraosseous administration into the proximal tibial metaphysis immediately before skin incision.
Drug: Intraosseous Vancomycin
Participants received 500 mg of vancomycin intravenously at the same preincision time point before below-knee amputation.
Drug: Intravenous Vancomycin
Participants received a single dose of 500 mg vancomycin diluted in 100 mL of 0.9% normal saline into the proximal tibial metaphysis using a sterile intraosseous vascular access system immediately before skin incision.
Participants received a single dose of 500 mg vancomycin intravenously at the same preincision time point before below-knee amputation.
Subcutaneous Soft-Tissue Vancomycin Concentration (mcg/g)
Vancomycin concentration in intraoperative stump subcutaneous tissue, measured by institutional laboratory assay.
Time frame: Perioperatively, during below-knee amputation
Serum Vancomycin Concentration (mcg/mL)
Vancomycin concentration in simultaneous venous serum, measured by institutional laboratory assay.
Time frame: Perioperatively, during below-knee amputation
Tissue-to-Serum Vancomycin Concentration Ratio
Ratio calculated by dividing stump subcutaneous tissue vancomycin concentration by simultaneous serum vancomycin concentration.
Time frame: Perioperatively, during below-knee amputation
White Blood Cell Count (10^3/uL)
Description: White blood cell count measured by laboratory blood test.
Time frame: Preoperative, postoperative 12 hours, postoperative day 1, day 3, day 7, and day 30
C-Reactive Protein Concentration (mg/L)
C-reactive protein concentration measured by laboratory blood test.
Time frame: Preoperative, postoperative 12 hours, postoperative day 1, day 3, day 7, and day 30
Procalcitonin Concentration (ng/mL)
Procalcitonin concentration measured by laboratory blood test.
Time frame: Preoperative, postoperative day 1, day 3, day 7, and day 30
Interleukin-6 Concentration (pg/mL)
Interleukin-6 concentration measured by laboratory blood test.
Time frame: Preoperative, postoperative day 1, day 3, day 7, and day 30
Visual Analog Scale Pain Score
Pain intensity was assessed using the Visual Analog Scale for pain, a 0-to-10 scale in which 0 indicates no pain and 10 indicates the worst imaginable pain. Higher scores indicate worse pain.
Time frame: Postoperative 6 hours, 24 hours, and day 3
Total Drain Output (mL)
Total postoperative drain output measured in milliliters.
Time frame: From postoperative day 0 to postoperative day 1
Peak ASEPSIS Wound Score
Peak wound score was assessed using the Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of deep tissues, Isolation of bacteria, and Stay as inpatient (ASEPSIS) wound scoring method. The minimum score is 0, and higher scores indicate worse wound healing or more severe surgical site infection. Scores greater than 20 indicate wound infection or clinically relevant wound-healing impairment, and scores greater than 40 indicate severe wound infection or poor wound-healing outcome.
Time frame: Through postoperative day 7
Participants With ASEPSIS Score >20
Number of participants with clinically relevant wound-healing impairment, defined as ASEPSIS score \>20.
Time frame: Through postoperative day 7
Plan to share: Yes — Individual participant data that underlie the results reported in the final article, after de-identification, will be made available to researchers whose proposed use of the data has been approved by a methodologically sound proposal.
Supporting information: Study protocol
This study is completed, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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Başakşehir Çam & Sakura City Hospital