Vancomycin Delivery Methods for Ankle Surgery

(IOTAA Trial)

Overseen By Blesson Varghese, BS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The Methodist Hospital Research Institute

Disqualifiers: Previous surgery, BMI > 40, Uncontrolled diabetes, Immunocompromised, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a contraindication (a medical reason not to use) to certain antibiotics like vancomycin, you may not be eligible to participate.

What data supports the effectiveness of the drug Vancomycin for ankle surgery?

Research shows that applying vancomycin powder directly to the surgical site can reduce infections in diabetic patients undergoing foot and ankle surgery. This suggests it might help prevent infections in similar surgeries. ^{1 2 3 4 5}

Is vancomycin safe for use in humans?

Vancomycin is generally safe for use in humans, but it can cause side effects like 'red neck syndrome' (redness and itching on the neck and upper back) if given too quickly through an IV. Serious side effects like kidney and ear problems are rare. ^{1 2 6 7 8}

How is the drug Vancomycin used differently in ankle surgery compared to other treatments?

Vancomycin is unique in ankle surgery because it can be applied as a powder directly to the surgical site, which may help reduce infections, especially in diabetic patients. This local application is different from the usual intravenous (through the vein) administration used for other infections. ^{1 2 9 10 11}

What is the purpose of this trial?

The purpose of this study is to compare two different antibiotic regimens and techniques during total ankle arthroplasty (TAA). Primary Objective: Comparable levels of vancomycin will be found in bone, soft tissue, and systemic samples between patient groups. Secondary Objective: Compare 30 day and 90 day post-operative complication rates (infection) between the control (standard IV administration of vancomycin) vs the interventional group (intraosseous administration of vancomycin). The investigators hypothesize that there will be no difference in complication (infection) rates between groups.

Research Team

Jason S Ahuero, MD

Principal Investigator

The Methodist Hospital Research Institute

Eligibility Criteria

This trial is for individuals undergoing total ankle arthroplasty who can safely receive vancomycin. It's not suitable for those with allergies to this antibiotic, other specific medical conditions that could interfere with the study, or those unable to follow the protocol.

Inclusion Criteria

I am scheduled for total ankle replacement surgery.

I am older than 18 years.

Patient is able to give informed consent to participate in the study. LAR consents will not be utilized for this study

Exclusion Criteria

Inability to administer the IO infusion

Vulnerable populations

I do not want to participate in the clinical trial.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either intraosseous or intravenous vancomycin during total ankle arthroplasty

1 day

1 visit (in-person, surgical procedure)

Follow-up

Participants are monitored for post-operative complication rates at 30 and 90 days

90 days

2 visits (in-person)

Treatment Details

Interventions

• Vancomycin

Trial Overview The study compares two ways of giving vancomycin during ankle surgery: directly into the bone (intraosseous) versus into a vein (intravenous). The goal is to see if both methods result in similar drug levels in bone and tissue and have comparable infection rates after surgery.

Participant Groups

Group I: Intraosseous Vancomycin Experimental Treatment 1 Intervention

IV antibiotics per physician's standard of care: Typically ancef or cefepime is started in pre-op within 1 hour of incision. IV Vancomycin will not be given preoperatively in this group. IO vancomycin is administered in the OR after sterile prep and draping has occurred (500mg in 100-150mL NS). IO Injection will take place into the medial malleolus.

Group II: Intravenous Vancomycin Active Control 1 Intervention

Patients will receive the orthopedic surgeon's standard of care pre-operative antibiotic regimen for TAA patients. This includes IV antibiotics (typically ancef or cefepime and vancomycin) will be started in the pre-operative period approximately 1 hour prior to incision (vancomycin dose weight-based at approximately 15mg/kg generally 1000-1750mg in 500mL normal saline (NS))

Vancomycin is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Vancocin for:

• Severe infections caused by susceptible strains of methicillin-resistant staphylococci
• Enterocolitis caused by Staphylococcus aureus
• Staphylococcal endocarditis

Approved in European Union as Vancomycin for:

• Severe infections caused by Gram-positive bacteria
• Endocarditis
• Peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD)

Approved in Canada as Vancomycin for:

• Severe infections caused by susceptible strains of methicillin-resistant staphylococci
• Enterocolitis caused by Staphylococcus aureus

Approved in Japan as Vancomycin for:

• Severe infections caused by Gram-positive bacteria
• Endocarditis

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Findings from Research

In a study of 162 diabetic patients undergoing foot and ankle surgery, the use of topically applied vancomycin powder reduced the overall likelihood of surgical site infections (SSIs) by 73%, particularly decreasing the risk of deep infections by 80%.

Topically applied vancomycin was found to be safe, inexpensive, and associated with a low rate of complications, suggesting it could be a beneficial preventive measure for high-risk diabetic patients during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topically Applied Vancomycin Powder Reduces the Rate of Surgical Site Infection in Diabetic Patients Undergoing Foot and Ankle Surgery. Wukich, DK., Dikis, JW., Monaco, SJ., et al.[2018]

Topically applied vancomycin may reduce deep infection rates in diabetic patients undergoing foot and ankle surgery, but evidence is limited for its use in total ankle arthroplasty or other foot and ankle procedures in the general population.

There is currently no consensus on the safety or efficacy of vancomycin powder in these procedures, as the recommendation is based on a single study and the overall evidence is insufficient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What Are the Benefits and Risks Associated With the Use of Vancomycin Powder in the Wound During Total Ankle Arthroplasty (TAA) or Other Foot and Ankle Procedures? Slullitel, G., Tanaka, Y., Rogero, R., et al.[2022]

In a study of 35 patients undergoing calcanectomy for infected diabetic heel ulcers, the use of intraoperative vancomycin powder was associated with a significantly higher rate of unplanned return to the operating room (84.6% vs 36.0% without vancomycin), indicating potential risks of this intervention.

Overall, the study found no clinical benefit from the application of vancomycin powder, as the healing rates and limb salvage rates were similar between the groups, suggesting that its use may not improve outcomes in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative Site Vancomycin Powder Application in Infected Diabetic Heel Ulcers With Calcaneal Osteomyelitis. Brodell, JD., Kozakiewicz, LN., Hoffman, SL., et al.[2022]

High concentrations of vancomycin (5000 µg/mL) significantly reduce the viability and proliferation of human mesenchymal stromal cells (hMSCs) during osteogenic differentiation, which is crucial for healing fractures and arthrodesis.

Surgeons should be cautious when using local vancomycin during foot and ankle surgeries, as it may impair the healing process due to its negative effects on hMSC viability and differentiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Vancomycin Treatment on Human Mesenchymal Stromal Cells During Osteogenic Differentiation. Bariteau, JT., Kadakia, RJ., Traub, BC., et al.[2019]

Local delivery of vancomycin directly into the medullary canal of long bones in a rat model resulted in low blood plasma concentrations, significantly reducing the risk of systemic toxicity compared to traditional intravenous administration.

This method effectively inhibited the development of osteomyelitis when administered concurrently with a bacterial inoculum, indicating that local intramedullary delivery can achieve high enough concentrations to prevent infection while maintaining safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local Intramedullary Delivery of Vancomycin Can Prevent the Development of Long Bone Staphylococcus aureus Infection. Loc-Carrillo, C., Wang, C., Canden, A., et al.[2022]

In a study of 117 hospitalized patients who experienced adverse reactions to vancomycin, only 10% developed similar reactions (fever, rash, or neutropenia) after switching to teicoplanin, indicating that teicoplanin is generally well-tolerated in this population.

However, 50% of patients who had neutropenia from vancomycin also experienced neutropenia after starting teicoplanin, suggesting that caution is needed when switching treatments for patients with a history of neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of teicoplanin in 117 hospitalized adults with previous vancomycin-induced fever, rash, or neutropenia: a retrospective chart review. Hung, YP., Lee, NY., Chang, CM., et al.[2013]

This phase III clinical trial aims to evaluate the effectiveness of local vancomycin powder in preventing surgical site infections (SSIs) after fracture surgery, specifically in patients with tibial plateau or pilon fractures, involving a total of 1000 participants (500 per treatment group).

The study will not only assess the rate of deep SSIs six months post-surgery but also analyze bacterial species and their susceptibilities, potentially leading to a better understanding of infection risks and improved prevention strategies in orthopedic trauma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter, Randomized, Controlled Trial (VANCO Study). OʼToole, RV., Joshi, M., Carlini, AR., et al.[2022]

Vancomycin is a highly effective antibiotic specifically targeting gram-positive bacteria, particularly useful for treating methicillin-resistant staphylococcal infections and gram-positive endocarditis, with a low risk of developing bacterial resistance due to its multiple modes of action.

While 'red neck syndrome' is a common side effect associated with rapid intravenous infusion, the overall toxicity of vancomycin is less significant than previously believed, and serious side effects like nephrotoxicity and ototoxicity are rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vancomycin: an update. Cheung, RP., DiPiro, JT.[2019]

Vancomycin is a powerful antibiotic that has been used since 1956 to treat serious staphylococcal infections, especially those resistant to penicillin, making it a crucial option when other antibiotics fail.

In the future, vancomycin may see increased use for treating methicillin-resistant Staphylococcus aureus (MRSA) infections, streptococcal endocarditis in penicillin-intolerant patients, infections from resistant organisms associated with prosthetic devices, and antibiotic-induced enterocolitis from Clostridium difficile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vancomycin. Geraci, JE., Hermans, PE.[2013]

In a study of 19 patients with acute prosthetic joint infections (PJI) after total knee arthroplasty (TKA), it was found that one-third of the bacteria were resistant to common antibiotics like gentamicin and tobramycin, while one-quarter were resistant to vancomycin.

The combination of tobramycin mixed into antibiotic cement and vancomycin powder effectively achieved intra-articular antibiotic concentrations that exceeded the minimum inhibitory concentrations for most bacteria, suggesting this strategy could optimize treatment for PJI after TKA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local delivery of tobramycin and vancomycin in primary total knee arthroplasty achieves minimum inhibitory concentrations for common bacteria causing acute prosthetic joint infection. Lawrie, CM., Jo, S., Barrack, T., et al.[2020]

Vancomycin, once set aside for other antibiotics, has seen a resurgence due to its effectiveness against serious infections like methicillin-resistant Staphylococcus aureus, but concerns about its efficacy and safety have also emerged.

Resistance to vancomycin has developed in various bacteria, prompting a renewed interest in optimizing its administration, potentially leading to a return to monitoring serum levels to ensure effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vancomycin: a history. Levine, DP.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Topically Applied Vancomycin Powder Reduces the Rate of Surgical Site Infection in Diabetic Patients Undergoing Foot and Ankle Surgery. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

What Are the Benefits and Risks Associated With the Use of Vancomycin Powder in the Wound During Total Ankle Arthroplasty (TAA) or Other Foot and Ankle Procedures? [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Intraoperative Site Vancomycin Powder Application in Infected Diabetic Heel Ulcers With Calcaneal Osteomyelitis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Impact of Vancomycin Treatment on Human Mesenchymal Stromal Cells During Osteogenic Differentiation. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Local Intramedullary Delivery of Vancomycin Can Prevent the Development of Long Bone Staphylococcus aureus Infection. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Tolerability of teicoplanin in 117 hospitalized adults with previous vancomycin-induced fever, rash, or neutropenia: a retrospective chart review. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter, Randomized, Controlled Trial (VANCO Study). [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Vancomycin: an update. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Vancomycin. [2013]

10. England pubmed.ncbi.nlm.nih.gov

Local delivery of tobramycin and vancomycin in primary total knee arthroplasty achieves minimum inhibitory concentrations for common bacteria causing acute prosthetic joint infection. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Vancomycin: a history. [2013]