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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods of administering the antibiotic vancomycin (also known as Vancocin) during ankle replacement surgery. The researchers aim to determine if there is a difference in how well the antibiotic reaches the bone and tissue and its impact on infection rates post-surgery. One group will receive the antibiotic intravenously (IV), while the other will receive it directly into the bone (intraosseous). The trial seeks participants planning to undergo total ankle replacement surgery who can consent to join the study. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

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 is the safety track record for vancomycin delivery methods in ankle surgery?

Research has shown that both intraosseous and intravenous vancomycin are generally safe during surgeries. One study found that intraosseous vancomycin, delivered directly into the bone, can lower infection risk and is well-tolerated. Another study suggested it might reduce joint infections more effectively than the intravenous method.

Intravenous vancomycin, administered through a vein, is a common and safe practice in surgeries and has been used for many years. It is known for its effectiveness against infections.

Extensive studies have identified no major safety concerns with either method. This evidence suggests that both treatments are safe options for preventing infections during ankle surgeries. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the Vancomycin Delivery Methods for Ankle Surgery trial because it explores different ways to administer vancomycin, a powerful antibiotic. Standard treatments usually involve giving vancomycin through an IV before surgery, but this trial is testing a new method: intraosseous (IO) delivery directly into the bone. This IO method could offer faster and more targeted antibiotic delivery right where it's needed, potentially reducing infection risks and improving recovery time. By comparing the IO method to the traditional IV approach, the trial aims to determine if this innovative delivery technique can enhance surgical outcomes.

What evidence suggests that these vancomycin delivery methods are effective for ankle surgery?

This trial compares two methods of vancomycin delivery for ankle surgery. Research has shown that vancomycin reduces infections during surgeries, including joint replacements. In this trial, one group receives intraosseous vancomycin, which involves applying vancomycin directly to the surgical area. Studies have found this method can lower infection rates in various bone surgeries. Another group receives intravenous (IV) vancomycin, a proven method for preventing infections in surgeries like ankle joint replacements. Both methods aim to deliver the antibiotic to necessary areas, helping to prevent infections after surgery. Overall, vancomycin effectively reduces the risk of infections during and after surgery. ^{1 2 3 6 7}

Who Is on the Research Team?

Jason S Ahuero, MD

Principal Investigator

The Methodist Hospital Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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 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]

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]

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]

Citations

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The purpose of this study is to compare two different antibiotic regimens and techniques during total ankle arthroplasty (TAA). Primary Objective: Comparable ...

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IO antibiotics in TKA are safe and effective alternatives to IV antibiotics. Large randomized clinical studies comparing infection rates and ...