Diabetic Amputation Foot Wound, Diabetic Foot Disease, Diabetic Foot Infection
Conditions
Keywords
Vancomycin, diabetic foot, intraosseoz, below-knee amputation
Brief summary
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.
Detailed description
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.
Interventions
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.
Sponsors
Başakşehir Çam & Sakura City Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
Because the route of vancomycin administration was apparent during surgery, the operating surgeon and operating room personnel were not blinded to group allocation. Laboratory personnel who measured vancomycin concentrations were blinded to treatment allocation. Postoperative clinical outcomes were recorded by a blinded assessor using predefined criteria; however, final clinical endpoint evaluation was not fully blinded because the study team included the operating surgeons.
Intervention model description
Prospective, randomized, parallel-assignment controlled clinical trial. Participants were randomly assigned in a 1:1 ratio to receive either intraosseous vancomycin or intravenous vancomycin before below-knee amputation.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Diagnosis of diabetes mellitus * Diabetic foot infection with distal ischemia * Scheduled to undergo below-knee amputation * Absence of a feasible further revascularization option, as determined by the cardiovascular surgery and interventional radiology teams * Adequate circulation at and proximal to the planned below-knee amputation level for stump healing * Ability to provide written informed consent
Exclusion criteria
* Documented allergy or hypersensitivity to vancomycin or cephalosporins * Dialysis dependence * Systemic vancomycin use within 48 hours before surgery * Previous Syme amputation or more proximal amputation * Planned amputation at a level other than below the knee * Incomplete perioperative pharmacokinetic sampling
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subcutaneous Soft-Tissue Vancomycin Concentration (mcg/g) | Perioperatively, during below-knee amputation | Vancomycin concentration in intraoperative stump subcutaneous tissue, measured by institutional laboratory assay. |
| Serum Vancomycin Concentration (mcg/mL) | Perioperatively, during below-knee amputation | Vancomycin concentration in simultaneous venous serum, measured by institutional laboratory assay. |
| Tissue-to-Serum Vancomycin Concentration Ratio | Perioperatively, during below-knee amputation | Ratio calculated by dividing stump subcutaneous tissue vancomycin concentration by simultaneous serum vancomycin concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| White Blood Cell Count (10^3/uL) | Preoperative, postoperative 12 hours, postoperative day 1, day 3, day 7, and day 30 | Description: White blood cell count measured by laboratory blood test. |
| C-Reactive Protein Concentration (mg/L) | Preoperative, postoperative 12 hours, postoperative day 1, day 3, day 7, and day 30 | C-reactive protein concentration measured by laboratory blood test. |
| Procalcitonin Concentration (ng/mL) | Preoperative, postoperative day 1, day 3, day 7, and day 30 | Procalcitonin concentration measured by laboratory blood test. |
| Interleukin-6 Concentration (pg/mL) | Preoperative, postoperative day 1, day 3, day 7, and day 30 | Interleukin-6 concentration measured by laboratory blood test. |
| Visual Analog Scale Pain Score | Postoperative 6 hours, 24 hours, and day 3 | 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. |
| Total Drain Output (mL) | From postoperative day 0 to postoperative day 1 | Total postoperative drain output measured in milliliters. |
| Peak ASEPSIS Wound Score | Through postoperative day 7 | 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. |
| Participants With ASEPSIS Score >20 | Through postoperative day 7 | Number of participants with clinically relevant wound-healing impairment, defined as ASEPSIS score \>20. |
Countries
Turkey (Türkiye)
Outcome results
None listed