IO vs IV Vancomycin for Preventing Infection in Knee Surgery

Overseen By Haley Goble, MHA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The Methodist Hospital Research Institute

Must not be taking: Immunosuppressants

Disqualifiers: Knee surgery, BMI >35, Diabetes, 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: 1

Duration: Immediate post-op

40 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on immunosuppressive medications, you may not be eligible to participate.

What data supports the effectiveness of the drug Vancomycin in preventing infection in knee surgery?

Research shows that using vancomycin directly in the bone (intraosseous) during knee surgery can lead to higher local antibiotic levels compared to traditional IV methods, potentially reducing infection rates. Additionally, intraosseous vancomycin has been associated with lower rates of joint infections after knee surgery without increasing complications. ^{1 2 3 4 5}

Is intraosseous vancomycin safe for use in knee surgery?

Research shows that using intraosseous vancomycin in knee surgery does not increase the risk of complications compared to the traditional intravenous method, suggesting it is generally safe for humans. ^{1 2 3 6 7}

How is the drug vancomycin used differently in this knee surgery trial?

In this trial, vancomycin is administered intraosseously (directly into the bone), which allows for higher local tissue concentrations compared to the traditional intravenous (IV) method, potentially improving its effectiveness in preventing infections during knee surgery. ^{1 3 5 8 9}

What is the purpose of this trial?

This trial is comparing two methods of giving an antibiotic during knee replacement surgery: through a vein and directly into the bone. It aims to see which method helps the antibiotic reach the knee area better and if it affects infection rates after surgery. Delivering antibiotics directly into the bone achieves higher local concentrations with fewer side effects and has been shown to be more effective for preventing infection following surgery.

Eligibility Criteria

This trial is for adults over 18 who are having their first knee replacement surgery without a tourniquet. They must understand the study and agree to participate. It's not for people with weak immune systems, uncontrolled diabetes (Hemoglobin A1C >7.5), allergies to vancomycin or similar antibiotics, BMI over 35, or those who've had previous knee surgeries.

Inclusion Criteria

Patient is undergoing a primary total knee arthroplasty.

Patient is able to understand the study design and intervention and gives informed consent to participate in the study. No LAR consents will be utilized for this study.

You had knee surgery without the use of a tourniquet.

Exclusion Criteria

Immunocompromised or immunosuppressed patients (HIV, Hep C, End-Stage Renal Disease, dialysis, transplant, chemo/radiation treatment in last 6 months, and immunosuppresive medications)

Uncontrolled Diabetes Mellitus type 1 or 2, defined as Hemoglobin A1C >7.5.

Contraindication to receiving vancomycin, cefepime, ancef, or other standard of care pre-operative antibiotic (allergy, medical issue, etc).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo total knee arthroplasty with either intraosseous or intravenous vancomycin administration

Immediate post-op

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including 30-day and 90-day post-operative complication rates

90 days

Multiple visits (in-person) as per standard of care

Treatment Details

Interventions

• Vancomycin

Trial Overview The study compares two ways of giving antibiotics during knee replacement surgery: directly into the bone (intraosseous) vs. into a vein (intravenous). The goal is to see which method better prevents infections after surgery without using a tourniquet.

Participant Groups

Group I: Intraosseous Vancomycin Administration 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 administered preoperatively in this group. * IO vancomycin is administered via an intraosseous cannulation device (Arrow EZ-IO; Teleflex, Morrisville, NC) in the OR after sterile prep and draping has occurred prior to skin incision (500mg in 150mL NS). * Injection will take place into the tibial tubercle (within a pre-specified region) immediately prior to incision.

Group II: Intravenous Vancomycin Administration Active Control 1 Intervention

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 (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 \[12,13\] generally 1000-1750mg in 500mL 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+

References

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

Clinical outcome evaluation of intraosseous vancomycin in total knee arthroplasty. [2022]

2. England pubmed.ncbi.nlm.nih.gov

2021 Chitranjan S. Ranawat Award: Intraosseous vancomycin reduces periprosthetic joint infection in primary total knee arthroplasty at 90-day follow-up. [2021]

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

Intraosseous Regional Administration of Vancomycin in Primary Total Knee Arthroplasty Does Not Increase the Risk of Vancomycin-Associated Complications. [2021]

4. Canada pubmed.ncbi.nlm.nih.gov

Intraarticular vancomycin decreased the risk of acute postoperative periprosthetic joint infection without increasing complication in primary total joint arthroplasty-a prospective study. [2023]

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

Vancomycin concentration in synovial fluid: direct injection into the knee vs. intravenous infusion. [2014]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intrawound vancomycin in primary hip and knee arthroplasty. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Decrease in acute periprosthetic joint infections incidence with vancomycin-loaded calcium sulfate beads in patients with non-modifiable risk factors. A randomized clinical trial. [2022]

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

Otto Aufranc Award: Intraosseous Vancomycin in Total Hip Arthroplasty - Superior Tissue Concentrations and Improved Efficiency. [2023]

9. Japan pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis comparing intrawound vancomycin powder and povidone iodine lavage in the prevention of periprosthetic joint infection of hip and knee arthroplasties. [2022]