Intraosseous Versus Intravenous Vancomycin in Below-Knee Amputation for Ischemic Diabetic Foot

NCT07338773 | Completed Phase 4

• 1 other identifier: E-96317027-514.10-285164594
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetic Foot Disease; Diabetic Foot Infection; Diabetic Amputation Foot Wound

Keywords

Vancomycin; diabetic foot; intraosseoz; below-knee amputation

Outcome Measures

Primary Outcomes (3)

• Subcutaneous Soft-Tissue Vancomycin Concentration (mcg/g)

  Vancomycin concentration in intraoperative stump subcutaneous tissue, measured by institutional laboratory assay.

  Perioperatively, during below-knee amputation

• Serum Vancomycin Concentration (mcg/mL)

  Vancomycin concentration in simultaneous venous serum, measured by institutional laboratory assay.

  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.

  Perioperatively, during below-knee amputation

Secondary Outcomes (8)

• White Blood Cell Count (10^3/uL)

  Preoperative, postoperative 12 hours, postoperative day 1, day 3, day 7, and day 30

• C-Reactive Protein Concentration (mg/L)

  Preoperative, postoperative 12 hours, postoperative day 1, day 3, day 7, and day 30

• Procalcitonin Concentration (ng/mL)

  Preoperative, postoperative day 1, day 3, day 7, and day 30

• Interleukin-6 Concentration (pg/mL)

  Preoperative, postoperative day 1, day 3, day 7, and day 30

• Visual Analog Scale Pain Score

  Postoperative 6 hours, 24 hours, and day 3

Study Arms (2)

Intraosseous Vancomycin

EXPERIMENTAL

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

Intravenous Vancomycin

ACTIVE COMPARATOR

Participants received 500 mg of vancomycin intravenously at the same preincision time point before below-knee amputation.

Drug: Intravenous Vancomycin

Interventions

Intravenous Vancomycin DRUG

Participants received a single dose of 500 mg vancomycin intravenously at the same preincision time point before below-knee amputation.

Intravenous Vancomycin

Intraosseous Vancomycin DRUG

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.

Intraosseous Vancomycin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Başakşehir Çam & Sakura City Hospital: lead

Study Sites (1)

Basaksehir Cam ve Sakura City Hospital

Istanbul, Istanbul, 34010, Turkey (Türkiye)

Location

Related Publications (1)

• Wininger AE, Gurusamy P, Sullivan TC, Serpelloni S, Taraballi F, Park KJ, Brown TS. Intraosseous Versus Intravenous Vancomycin in Tourniquetless Primary Total Knee Arthroplasty: A Randomized Trial. J Arthroplasty. 2024 Sep;39(9 Suppl 2):S224-S228. doi: 10.1016/j.arth.2024.02.083. Epub 2024 Mar 8.

  PMID: 38462143 BACKGROUND

MeSH Terms

Conditions

Diabetic Foot

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Orthopaedic surgeon

Model Details: 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.

Study Record Dates

• First Submitted: January 4, 2026
• First Posted: January 14, 2026
• Study Start: August 6, 2025
• Primary Completion: June 15, 2026
• Study Completion: June 21, 2026
• Last Updated: July 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available beginning 2 months and ending 12 months after article publication.
• Access Criteria: Data will be shared with researchers who provide a methodologically sound proposal. Proposals should be directed to the corresponding author at lezginmert@gmail.com

Locations

TU (1)