Antibiotic Prophylaxis for Knee Replacement Surgery

Not currently recruiting at 13 trial locations

Overseen By Jennifer Friend

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Duke University

Disqualifiers: Pregnancy, Psychiatric disorder, Severe dementia, 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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the best method for using antibiotics to prevent infections in individuals undergoing knee replacement surgery. Researchers are testing whether a single dose of the antibiotic cefazolin before surgery suffices or if additional doses after surgery prove more effective. This trial targets those planning elective knee replacement due to conditions like osteoarthritis or other joint issues, without open wounds or active infections in the knee area. Participants must be willing to adhere to the study's schedule and guidelines. As a Phase 4 trial, this research involves an FDA-approved treatment and seeks to enhance its benefits for 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. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for these treatments?

Research shows that cefazolin, the antibiotic under study, is usually well-tolerated during knee replacement surgeries. Studies have demonstrated that using cefazolin to prevent surgery-related infections helps maintain low infection rates when combined with effective infection control practices. One study found that allergic reactions to cefazolin are rare, occurring within 72 hours after surgery in only a small number of patients.

For those allergic to cefazolin, alternatives like vancomycin and clindamycin are available. A study comparing vancomycin with cefazolin noted a possible increased risk of infection with vancomycin, but these results were not conclusive.

Overall, evidence suggests that cefazolin is a safe choice for most patients, with side effects or allergic reactions being uncommon. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these prophylactic antibiotic regimens for knee replacement surgery because they explore different dosing strategies of cefazolin to optimize infection prevention. Unlike the standard approach, which typically involves multiple doses over a longer period, Study Group 1 receives just a single dose before surgery, potentially simplifying care and reducing antibiotic exposure. Study Group 2, on the other hand, adds two additional doses within 24 hours post-surgery, which might enhance protection against infection. This trial aims to determine the most effective balance between minimizing antibiotic use and maximizing infection prevention, which could lead to tailored, effective protocols for patients undergoing knee replacement.

What evidence suggests that this trial's treatments could be effective for preventing infections in knee replacement surgery?

This trial will compare two antibiotic prophylaxis strategies using cefazolin for knee replacement surgery. Studies have shown that cefazolin effectively reduces the risk of infections around the joint during these surgeries. Research indicates that cefazolin can lower infection rates by 32% compared to other antibiotics. It is often considered the preferred antibiotic for preventing infections in knee surgeries. Administering antibiotics before surgery is crucial in infection prevention. Additionally, cefazolin plays a key role in current strategies to prevent infections soon after knee replacement, underscoring its importance in keeping surgery sites free from infection. ^{4 6 7 8 9}

Who Is on the Research Team?

Thorsten Seyler, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for adults over 18 without open wounds or active infections on the leg where knee replacement surgery will happen. It's not for those unable to consent, with severe dementia, drug abuse (except prescription cannabinoids), extreme surgical risk (ASA score of 5 & 6), emergency cases, prior septic arthritis, pregnancy, certain psychiatric conditions, or if they can't follow the study plan.

Inclusion Criteria

I am scheduled for knee replacement surgery due to arthritis or injury.

I do not have an infection in the leg or joint that needs surgery.

I have no open wounds on my leg that needs surgery.

Exclusion Criteria

I have not used antibiotic powder or beads in my surgical wound.

I have had a knee infection in the past.

I did not need extra doses of medication during surgery unless I lost a lot of blood.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Antibiotic Administration

Participants receive a single weight-based dose of prophylactic cefazolin antibiotic intravenously within less than 60 minutes prior to skin incision

1 day

1 visit (in-person)

Postoperative Antibiotic Administration

Participants in Group #2 receive two additional weight-based doses of cefazolin within 24 hours postoperatively

1 day

Follow-up

Participants are monitored for safety and effectiveness after surgery

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cefazolin

Trial Overview The study tests if giving antibiotics within an hour before cutting or continuing them for a day after knee replacement surgery prevents joint and site infections better. Duke University recruits patients undergoing elective primary TKA and unilateral knee arthroplasty.

How Is the Trial Designed?

Group I: Study Group 2 Experimental Treatment 1 Intervention

Patients in Group #2 will receive a single weight-based dose of prophylactic cefazolin antibiotic that is administered intravenously within less than 60 minutes prior to skin incision in elective total knee arthroplasty. In addition, two weight-based doses of cefazolin will be administered within 24 hours postoperatively. \< 120 kg - patients will receive 2 grams of cefazolin ≥ 120 kg - patient will receive 3 grams of cefazolin Patients with documented allergy/anaphylactic reaction to penicillin or cephalosporin may receive intravenous vancomycin monotherapy or dual therapy with vancomycin and gentamicin as an alternative. If allergic, patients will also receive two weight-based doses vancomycin postoperatively but not gentamicin postoperatively. In addition, the use of clindamycin as an alternative is also permitted. Vancomycin schedule: one dose preoperatively, one dose 8-12 h postoperatively, one dose 24 h postoperatively (opt.).

Group II: Study Group 1 Experimental Treatment 1 Intervention

Patients in Group #1 will receive a single weight-based dose of prophylactic cefazolin antibiotic that is administered intravenously within less than 60 minutes prior to skin incision in elective total knee arthroplasty. No further antibiotic administration will be given. \< 120 kg - patients will receive 2 grams of cefazolin ≥ 120 kg - patient will receive 3 grams of cefazolin Patients with documented allergy/anaphylactic reaction to penicillin or cephalosporin may receive intravenous vancomycin monotherapy or dual therapy with vancomycin and gentamicin as an alternative. In addition, the use of clindamycin as an alternative is also permitted at a minimum recommended dose.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

American Association of Hip and Knee Surgeons

Collaborator

Trials

4

Recruited

2,300+

American Association of Hip and Knee Surgeons

Collaborator

Trials

4

Recruited

2,300+

Orthopedic Research and Education Foundation

Collaborator

Trials

23

Recruited

6,200+

Published Research Related to This Trial

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]

In a study of 1128 total hip and knee arthroplasties, patients receiving cefazolin had significantly lower rates of surgical site infections (SSIs) compared to those receiving clindamycin or vancomycin (0.9% vs 3.8%).

The use of cefazolin did not result in a higher frequency of interoperative hypersensitivity reactions compared to clindamycin or vancomycin, suggesting it is a safe option for patients labeled as beta-lactam allergic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefazolin vs Second-line Antibiotics for Surgical Site Infection Prevention After Total Joint Arthroplasty Among Patients With a Beta-lactam Allergy. Norvell, MR., Porter, M., Ricco, MH., et al.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2352344125000950

Cefazolin Is the Most Effective Perioperative Antibiotic to ... Rates of periprosthetic joint infection (PJI) are 32% lower when cefazolin (ancef, kefzol) is used perioperatively over other antibiotics.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9047071/

Cefazolin remains the linchpin for preventing acute ... Cefazolin remains the linchpin for preventing acute periprosthetic joint infection following primary total knee arthroplasty · Abstract.

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2822773

Tourniquet Use and Local Tissue Concentrations of ... Prophylactic administration of intravenous (IV) antibiotics before skin incision is a crucial component in the prevention of PJI in arthroplasty ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2301401

Trial of Vancomycin and Cefazolin as Surgical Prophylaxis ... The addition of vancomycin to cefazolin prophylaxis was not superior to placebo for the prevention of surgical-site infections in arthroplasty.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03283878

Study Details | NCT03283878 | Antibiotic Prophylaxis in ... A study that will compare the effectiveness of various perioperative strategies for antibiotic delivery as prophylaxis for periprosthetic joint infections (PJI)

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38677347/

Perioperative Cefazolin for Total Joint Arthroplasty Patients ... The primary outcome was the rate of allergic reactions within 72 hours postoperatively. Secondary outcomes included the rates of superficial ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1201971211001883

Outcome of cefazolin prophylaxis for total knee arthroplasty ... Our data suggest that antimicrobial prophylaxis using only cefazolin can maintain low SSI rates if other important infection management measures are employed.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05604157?term=GRAMAXIN&rank=4

Ancef Dosage in Knee Arthroplasty : Tourniquet Clinical Trial Although rare, with reported rates of 0.5-2% within 2 years, periprosthetic joint infection (PJI) is a devastating complication with serious morbidity.

9. arthroplastyjournal.org arthroplastyjournal.org/article/S0883-5403(24)00381-4/fulltext

Perioperative Cefazolin for Total Joint Arthroplasty Patients ... The purpose of this study was to determine the safety of perioperative cefazolin in PCNA patients undergoing primary TJA.