Diabetic Foot DiseasePhase 4NCT07338773
Intraosseous Versus Intravenous Vancomycin in Below-Knee Amputation for Ischemic Diabetic Foot
A Phase 4 study testing Intraosseous Vancomycin and Intravenous Vancomycin in people with Diabetic Foot Disease and Diabetic Foot Infection, run by Başakşehir Çam & Sakura City Hospital at 1 site in Turkey (Türkiye).
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Foot Disease, Diabetic Foot Infection, Diabetic Amputation Foot Wound
- What is being tested?
- Intraosseous Vancomycin and Intravenous Vancomycin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 6 Aug 2025to 21 Jun 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Basaksehir Cam ve Sakura City Hospital
Istanbul, Istanbul, 34010
About this study
Official title: Does Intraosseous Compared With Intravenous Vancomycin Alter Local Exposure, Systemic Safety, and Early Outcomes in Patients With Ischemic Diabetic Foot Undergoing Below-knee Amputation? A Randomized Trial
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.
Read the 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.
- Being tested
- Intraosseous Vancomycin, Intravenous Vancomycin
- Keywords
- Vancomycin, diabetic foot, intraosseoz, below-knee amputation
- Medical subject headings
- Diabetic Foot
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intraosseous VancomycinDrug
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.
Intravenous VancomycinDrug
Participants received a single dose of 500 mg vancomycin intravenously at the same preincision time point before below-knee amputation.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Intraosseous Vancomycin |
| Intravenous Vancomycin | Active comparator | Participants received 500 mg of vancomycin intravenously at the same preincision time point before below-knee amputation. Receives: Drug: Intravenous Vancomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subcutaneous Soft-Tissue Vancomycin Concentration (mcg/g)
Vancomycin concentration in intraoperative stump subcutaneous tissue, measured by institutional laboratory assay.
Measured: Perioperatively, during below-knee amputation
Serum Vancomycin Concentration (mcg/mL)
Vancomycin concentration in simultaneous venous serum, measured by institutional laboratory assay.
Measured: 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.
Measured: Perioperatively, during below-knee amputation
Secondary outcomes (8)
White Blood Cell Count (10^3/uL)
Description:
White blood cell count measured by laboratory blood test.
Measured: 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.
Measured: 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.
Measured: Preoperative, postoperative day 1, day 3, day 7, and day 30
Interleukin-6 Concentration (pg/mL)
Interleukin-6 concentration measured by laboratory blood test.
Measured: 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.
Measured: Postoperative 6 hours, 24 hours, and day 3
Total Drain Output (mL)
Total postoperative drain output measured in milliliters.
Measured: 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.
Measured: Through postoperative day 7
Participants With ASEPSIS Score >20
Number of participants with clinically relevant wound-healing impairment, defined as ASEPSIS score >20.
Measured: Through postoperative day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2026
- Study start6 Aug 2025
- Primary completion15 Jun 2026
- Study completion21 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic Foot DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Başakşehir Çam & Sakura City Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Lezgin Mert, Başakşehir Çam & Sakura City Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07338773
- Sponsor's protocol ID
- E-96317027-514.10-285164594
- Status last verified
- Jul 2026
- First submitted
- 4 Jan 2026
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Publications
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.
PubMed 38462143
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Intraosseous Compared With Intravenous Vancomycin Alter Local Exposure, Systemic Safety, and Early Outcomes in Patients With Ischemic Diabetic Foot Undergoing Below-knee Amputation? A Randomized Trial
- ClinicalTrials.gov ID
- NCT07338773
- Acronym / sponsor ID
- E-96317027-514.10-285164594
- Keywords
- Vancomycin, diabetic foot, intraosseoz, below-knee amputation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Başakşehir Çam & Sakura City HospitalOther government
- Study start
- 6 Aug 2025 (actual)
- Primary completion
- 15 Jun 2026 (actual)
- Study completion
- 21 Jun 2026 (actual)
- First posted
- 14 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Intraosseous Vancomycin | Experimental | Drug: Intraosseous VancomycinParticipants 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. |
| Intravenous Vancomycin | Active comparator | Drug: Intravenous VancomycinParticipants received 500 mg of vancomycin intravenously at the same preincision time point before below-knee amputation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intraosseous VancomycinParticipants 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. | Drug | Intraosseous Vancomycin |
| Intravenous VancomycinParticipants received a single dose of 500 mg vancomycin intravenously at the same preincision time point before below-knee amputation. | Drug | Intravenous Vancomycin |
Primary outcome
Subcutaneous Soft-Tissue Vancomycin Concentration (mcg/g)
Time frame: Perioperatively, during below-knee amputation
Vancomycin concentration in intraoperative stump subcutaneous tissue, measured by institutional laboratory assay.
Serum Vancomycin Concentration (mcg/mL)
Time frame: Perioperatively, during below-knee amputation
Vancomycin concentration in simultaneous venous serum, measured by institutional laboratory assay.
Tissue-to-Serum Vancomycin Concentration Ratio
Time frame: Perioperatively, during below-knee amputation
Ratio calculated by dividing stump subcutaneous tissue vancomycin concentration by simultaneous serum vancomycin concentration.
8 secondary outcomes
White Blood Cell Count (10^3/uL)
Time frame: Preoperative, postoperative 12 hours, postoperative day 1, day 3, day 7, and day 30
C-Reactive Protein Concentration (mg/L)
Time frame: Preoperative, postoperative 12 hours, postoperative day 1, day 3, day 7, and day 30
Procalcitonin Concentration (ng/mL)
Time frame: Preoperative, postoperative day 1, day 3, day 7, and day 30
Interleukin-6 Concentration (pg/mL)
Time frame: Preoperative, postoperative day 1, day 3, day 7, and day 30
Visual Analog Scale Pain Score
Time frame: Postoperative 6 hours, 24 hours, and day 3
Total Drain Output (mL)
Time frame: From postoperative day 0 to postoperative day 1
Peak ASEPSIS Wound Score
Time frame: Through postoperative day 7
Participants With ASEPSIS Score >20
Time frame: Through postoperative day 7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
- Background: PubMed 38462143Wininger 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.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Intraosseous Vancomycin and Intravenous Vancomycin in people with Diabetic Foot Disease and Diabetic Foot Infection, run by Başakşehir Çam & Sakura City Hospital at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Subcutaneous Soft-Tissue Vancomycin Concentration (mcg/g) (time frame: Perioperatively, during below-knee amputation). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07338773, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.