IO vs IV Antibiotics for Total Knee Replacement

Overseen By Thomas Sullivan

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: The Methodist Hospital Research Institute

Disqualifiers: Bmi > 40, Uncontrolled diabetes, others

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

Compensation: Varies

Number of Visits: 3

Duration: 1 day (surgical procedure)

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 antibiotics during knee replacement surgery to determine which better prevents infections and reduces complications. Participants will receive antibiotics either through a vein (IV) or through the bone (IO). The trial seeks adults planning a total knee replacement who can take vancomycin or cefazolin without issues. As a Phase 1, Phase 2 trial, this research aims to understand the treatment's effects and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in knee surgery.

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 received or are scheduled to receive IV vancomycin or cefazolin within 7 days before the procedure, you may not be eligible to participate.

What prior data suggests that these antibiotic administration techniques are safe for total knee replacement surgery?

Research has shown that intraosseous (IO) methods for delivering antibiotics like vancomycin and cefazolin are safe and effective in preventing infections during total knee replacement surgeries. Studies have found that IO vancomycin reduces infection risk by 69% compared to traditional methods, leading to better outcomes over one to two years. Another study confirmed that IO antibiotics safely prevent infections in joint surgeries.

Regarding safety, IO vancomycin has been successfully used in other surgeries and serves as a reliable alternative to intravenous (IV) methods. This indicates that the IO method is well-tolerated, with no major safety concerns reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using intraosseous (IO) administration of antibiotics for total knee replacement because it offers a unique delivery method compared to the standard intravenous (IV) approach. Unlike IV antibiotics, which are given through the vein, IO antibiotics are injected directly into the bone, potentially leading to faster and more direct absorption at the surgical site. This method might reduce the risk of infection more effectively, providing a targeted approach that could enhance recovery and outcomes for patients undergoing knee surgery.

What evidence suggests that this trial's antibiotic administration techniques could be effective for total knee replacement?

This trial will compare the effectiveness of intraosseous (IO) versus standard intravenous (IV) administration of vancomycin and cefazolin in preventing infections after total knee replacement surgery. Research has shown that IO vancomycin and cefazolin can effectively prevent infections, with one study finding a 69% reduction in infection rates compared to other methods. Reviews of multiple studies have found that IO delivery results in higher antibiotic levels in tissues and reduces infection rates more than standard IV methods. Additionally, IO vancomycin is considered safe and effective for patients undergoing knee surgery. These findings suggest that IO administration could be a promising way to reduce infections after surgery. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults scheduled for primary total knee replacement surgery at Houston Methodist Hospital. Participants must be eligible for the procedure and willing to receive antibiotics either through their veins (IV) or directly into the bone (IO). Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

I understand the study and agree to participate.

I am scheduled for a first-time knee replacement surgery.

Exclusion Criteria

I cannot take vancomycin or cefazolin due to health reasons.

Body mass index (BMI) > 40

My diabetes is not under control (A1c > 7.5%).

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 administration of vancomycin and cefazolin during the total knee arthroplasty procedure

1 day (surgical procedure)

1 visit (in-person)

Follow-up

Participants are monitored for postoperative infections and wound complications

90 days

2 visits (in-person) at 30 and 90 days postop

What Are the Treatments Tested in This Trial?

Interventions

• Intraosseous (IO) Cefazolin and Vancomycin

Trial Overview The study compares two ways of giving antibiotics during knee replacement surgery: IV Vancomycin and Cefazolin versus IO Vancomycin and Cefazolin. It aims to see which method better prevents infection without increasing complications post-surgery.

How Is the Trial Designed?

Group I: Intraosseous Administration of Vancomycin and Cefazolin Experimental Treatment 2 Interventions

Intraosseous vancomycin plus cefazolin is administered via an intraosseous cannulation device (Arrow EZ-IO; Teleflex, Morrisville, NC) in the OR after sterile prep of the leg and draping has occurred prior to skin incision and after the tourniquet has been inflated. The injection will take place into the tibial tubercle, which is a known safe IO injection site. The IO injection will include 500mg of vancomycin and a 1g dose of cefazolin, previously used in prior IO studies of cefazolin.

Group II: Standard IV Administration of Vancomycin and Cefazolin Active Control 2 Interventions

Patients will receive the Houston Methodist Hospital orthopedic surgery standard of care pre-operative antibiotic regimen for primary total knee arthroplasty patients. This includes IV antibiotics cefazolin will be started in the pre-operative period approximately 1 hour prior to incision. The cefazolin dose is generally 2g if patient is under 120kg, and 3g is the patient is above 120kg in line with guidelines. Vancomycin IV administration will be dosing will be weight-based at approximately 15mg/kg generally 1000-1750mg in 500mL NS.

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Published Research Related to This Trial

In a study involving 18 patients undergoing total knee arthroplasty, a 2 g dose of intravenous cefazolin resulted in significantly higher intraosseous concentrations compared to a 1 g dose, indicating a potential for improved drug delivery to the surgical site.

Despite the increased concentrations of cefazolin with the 2 g dose, there was no corresponding increase in its effectiveness against Staphylococcus aureus growth, suggesting that higher doses may not necessarily enhance antibacterial efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraosseous concentration and inhibitory effect of different intravenous cefazolin doses used in preoperative prophylaxis of total knee arthroplasty. Angthong, C., Krajubngern, P., Tiyapongpattana, W., et al.[2018]

Periprosthetic infections, particularly from Staphylococcus aureus and Staphylococcus epidermidis, occur in 0.4-2% of total knee arthroplasty patients, making effective antibiotic prophylaxis crucial.

The study suggests that administering cefazolin 10 to 30 minutes before tourniquet inflation could optimize its peak concentrations in both blood and bone, enhancing its effectiveness in preventing infections during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefazolin should be administered maximum 30 min before incision in total knee arthroplasty when tourniquet is used. Bicanic, G., Crnogaca, K., Barbaric, K., et al.[2014]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06640491

Intraosseous (IO) Cefazolin and Vancomycin in Primary ... The goal of this clinical trial is to compare the efficacy of intravenous (IV) and intraosseous (IO) antibiotic administration techniques during primary ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12589950/

Intraosseous Vancomycin in Total Knee Arthroplasty IOV is an effective adjunctive treatment for preventing infection in primary TKA, with this study showing a 69% decreased odds of infection when compared with ...

3. mdpi.com mdpi.com/1648-9144/61/10/1750

A Systematic Review and Meta-Analysis Recent systematic reviews have reported that IO antibiotic delivery achieves higher tissue concentrations and reduces PJI rates more effectively than standard ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S088354032500453X

Intraosseous Vancomycin Reduces the Rate of ... Use of IO vancomycin infusion is a safe and effective alternative to IV administration for patients undergoing aseptic revision TKA.

5. arthroplastyjournal.org arthroplastyjournal.org/article/S0883-5403(25)00453-X/abstract

The AAHKS Best Podium Presentation Research Award Use of IO vancomycin infusion is a safe and effective alternative to IV administration for patients undergoing aseptic revision TKA.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S088354032500467X

Superior Clinical Results With Intraosseous Vancomycin in ... Intraosseous vancomycin demonstrated superior clinical outcomes over IV vancomycin with a reduced incidence of PJI at 90-day, 1- and 2-year follow-up after ...