Infection Prophylaxis for Joint Replacement

(PREVENT-iT Trial)

Overseen By Lindsay Maharaj, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hamilton Health Sciences Corporation

Must not be taking: Antibiotics

Disqualifiers: Infection, Fracture, Bilateral TJR, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

21006 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if different antiseptic solutions and antibiotics used during joint replacement surgery can reduce infections that necessitate additional surgery. It compares six combinations of wound washes and antibiotics to identify the most effective option. The trial includes antiseptic solutions like Chlorhexidine Gluconate and Povidone-Iodine, along with antibiotics such as Vancomycin Hydrochloride. It seeks participants undergoing their first or a non-infected revision hip or knee replacement who have not recently taken antibiotics. Researchers will monitor participants for a year to check for infections. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in surgical infection prevention.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken antibiotics in the two weeks before your joint replacement surgery.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments tested in this trial—Povidone-Iodine, Chlorhexidine Gluconate, and Vancomycin—are generally safe and have been used in similar surgeries before.

Studies have found that Povidone-Iodine, used as a cleaning solution, effectively reduces infections after joint surgeries. For instance, one study showed that only 0.4% of patients who received Povidone-Iodine developed infections, compared to 3.4% of those who did not, highlighting its potential to lower infection risk.

Chlorhexidine Gluconate, another antiseptic solution, is also commonly used in surgeries. Research indicates it is safe and effective for preventing infections in joint surgeries, with very few reports of side effects.

Vancomycin, an antibiotic, is applied directly to the surgical site to prevent infections. Evidence suggests it can significantly reduce infection rates without serious side effects when used in the right amounts.

These treatments are in a late-stage trial, indicating they have already undergone extensive safety testing. Participants can feel reassured by this background and the existing safety data. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for infection prophylaxis in joint replacement because they explore new combinations and applications of existing antiseptics and antibiotics. Unlike the standard practice which often uses chlorhexidine or iodine alone, these methods combine povidone-iodine or chlorhexidine gluconate lavage solutions with vancomycin to enhance infection prevention. This trial investigates the timing and method of applying vancomycin directly to the surgical site, which could offer a more targeted approach to infection control, potentially reducing post-surgical infections more effectively than current standard practices. By evaluating the direct application of vancomycin with antiseptic lavages, researchers aim to improve outcomes in joint replacement surgeries.

What evidence suggests that this trial's treatments could be effective in reducing infections after joint replacement surgery?

This trial will evaluate different antiseptic washes and their effectiveness in preventing infections during joint replacement surgeries. Research has shown that povidone-iodine washes can significantly reduce infection risk after joint replacement surgery, outperforming saline solutions. In this trial, some participants will receive povidone-iodine lavage, while others will receive chlorhexidine gluconate, which also effectively reduces surgical site infections by lowering bacteria levels over time. Additionally, some treatment arms will include the application of vancomycin directly into the surgical wound, which has been shown to decrease the risk of deep wound infections. Using these antiseptic washes along with vancomycin has proven very effective in preventing infections during joint surgeries. Overall, these treatments have shown promise in reducing infections that can lead to complications after joint replacement. ^{1 6 7 8 9}

Who Is on the Research Team?

Thomas J Wood, MD, FRCSC

Principal Investigator

Hamilton Health Sciences / McMaster University

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are having their first or a revision joint replacement surgery and have no issues with using antiseptics or antibiotics. They must understand the study and agree to follow its rules.

Inclusion Criteria

Informed consent (participant or substitute decision maker) obtained and willing to comply with the protocol

I have no health conditions that prevent me from participating in the study.

I am having my first or a follow-up joint replacement without infection.

Exclusion Criteria

I am having surgery for a broken bone.

I have open infected wounds on my limb.

Currently enrolled in a study that does not permit co-enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo total joint replacement surgery with randomized antiseptic and antibiotic treatments

1 day

1 visit (in-person)

Follow-up

Participants are monitored for infection rates and safety for one year after surgery

52 weeks

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Chlorhexidine Gluconate
• Povidone-Iodine
• Vancomycin Hydrochloride

Trial Overview

The trial tests if washing surgical sites with antiseptic solutions like Chlorhexidine Gluconate, Saline, Povidone-Iodine, and applying Vancomycin Hydrochloride antibiotic can prevent infections after joint replacement surgery.

How Is the Trial Designed?

Group I: Saline Lavage Solution and Vancomycin Experimental Treatment 2 Interventions

The study lavage solution (saline) is the final lavage and is to be poured in and left for 3 minutes then removed by suction. Two grams of vancomycin is applied to the deep joint (to arthrotomy in knee and deep to fascia in hip) following removal of the study lavage solution and immediately prior to closure.

Group II: Povidone-Iodine 0.35% Lavage Solution and Vancomycin Experimental Treatment 2 Interventions

The study lavage solution (povidone-iodine) is the final lavage and is to be poured in and left for 3 minutes then removed by suction. Two grams of vancomycin is applied to the deep joint (to arthrotomy in knee and deep to fascia in hip) following removal of the study lavage solution and immediately prior to closure. The study lavage solution will be a total volume of 1 litre, made with sterile isotonic saline.

Group III: Povidone-Iodine 0.35% Lavage Solution Experimental Treatment 1 Intervention

The study lavage solution (povidone-iodine) is the final lavage and is to be poured in and left for 3 minutes then removed by suction. The study lavage solution will be a total volume of 1 litre, made with sterile isotonic saline.

Group IV: Chlorhexidine Gluconate 0.05% Lavage Solution and Vancomycin Experimental Treatment 2 Interventions

The study lavage solution (chlorhexidine gluconate) is the final lavage and is to be poured in and left for 3 minutes then removed by suction. Two grams of vancomycin is applied to the deep joint (to arthrotomy in knee and deep to fascia in hip) following removal of the study lavage solution and immediately prior to closure. The study lavage solution will be a total volume of 1 litre, made with sterile isotonic saline.

Group V: Chlorhexidine Gluconate 0.05% Lavage Solution Experimental Treatment 1 Intervention

The study lavage solution (chlorhexidine-gluconate) is the final lavage and is to be poured in and left for 3 minutes then removed by suction. The study lavage solution will be a total volume of 1 litre, made with sterile isotonic saline.

Group VI: Saline Lavage Solution Active Control 1 Intervention

The study lavage solution (saline) is the final lavage and is to be poured in and left for 3 minutes then removed by suction. The study lavage solution will be a total volume of 1 litre.

Who Is Running the Clinical Trial?

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Recruited

345,000+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Ontario Clinical Oncology Group (OCOG)

Collaborator

Trials

65

Recruited

42,000+

Published Research Related to This Trial

The study found that both 1% chlorhexidine-gluconate/61% ethanol (CHG/Ethanol) emollient and 7.5% povidone-iodine (PVI) scrub had similar antimicrobial effects, with no significant difference in the number of microorganisms present immediately after surgical scrubs and after operations.

However, CHG/Ethanol emollient was associated with better skin condition and higher satisfaction among users compared to PVI, suggesting it may be a preferable option for surgical scrubs in terms of user comfort and skin health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of a waterless, scrubless chlorhexidine gluconate/ethanol surgical scrub and povidone-iodine for antimicrobial efficacy]. Choi, JS.[2019]

In a study involving 39 volunteers, chlorhexidine gluconate (Hibiclens) was found to be significantly more effective than povidone-iodine (E-Z Scrub 201) and chloroxylenol (ParaSoft) in reducing bacterial counts during 2-minute surgical scrubs.

The effectiveness of chlorhexidine increased over time, showing greater reductions in bacterial counts at all sampling times compared to the other two antiseptics, indicating its superior antibacterial efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative antibacterial efficacy of a 2-minute surgical scrub with chlorhexidine gluconate, povidone-iodine, and chloroxylenol sponge-brushes. Aly, R., Maibach, HI.[2019]

ChloraPrep™ significantly reduces the time required for surgical site skin preparation in total hip arthroplasty, averaging 3.5 minutes compared to 13.5 minutes for Betadine®, which can enhance operating room efficiency.

The cost of using ChloraPrep™ for skin preparation is substantially lower, averaging €46.8 per patient compared to €155 for Betadine®, indicating potential health economic benefits alongside its recognized effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical solutions for preoperative skin preparation in total hip arthroplasty: A cost-effectiveness analysis of Betadine® and Chloraprep™. Rougereau, G., Chatelain, L., Terracher, R., et al.[2022]

The use of 2% chlorhexidine-impregnated cloths significantly reduces infection rates in patients undergoing primary lower extremity total joint arthroplasties, as shown in a systematic review and meta-analysis.

Chlorhexidine cloths are effective for prophylaxis not only in knee and hip arthroplasties but also in various other surgical procedures, highlighting their broad applicability in preventing periprosthetic infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Utility of Chlorhexidine Cloth Use for the Prevention of Surgical Site Infections in Total Hip Arthroplasty and Surgical as well as Basic Science Applications: A Meta-Analysis and Systematic Review. Chen, Z., Mont, MA.[2022]

The review analyzed six randomized controlled trials to compare the antimicrobial efficacy and safety of various antiseptics for preoperative skin preparation, including combinations of chlorhexidine gluconate and isopropyl alcohol, and other antiseptics like povidone-iodine.

Results indicated that 2% chlorhexidine gluconate combined with 70% isopropyl alcohol (ChloraPrep) showed superior immediate and persistent antimicrobial efficacy compared to other antiseptics, suggesting it may be the best option for preventing nosocomial infections during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analyses comparing the antimicrobial activity and safety of current antiseptic agents: a review. Hibbard, JS.[2019]

In a study involving 446 catheters placed in 390 patients, 2% chlorhexidine gluconate−alcohol (CHG) was found to significantly reduce the growth of bacteria at catheter insertion sites compared to 10% povidone-iodine−alcohol (PVI), with detection rates of flora at day 7 being 6.3% for CHG versus 26.6% for PVI.

The incidence of catheter-related bloodstream infections (CRBSIs) was lower in the CHG group (0 events per 1000-catheter-days) compared to the PVI group (2.15 events per 1000-catheter-days), suggesting that CHG may be a more effective antiseptic in preventing infections associated with central venous catheters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Efficacy of 2% Chlorhexidine Gluconate-Alcohol and 10% Povidone-Iodine-Alcohol against Catheter-Related Bloodstream Infections and Bacterial Colonization at Central Venous Catheter Insertion Sites: A Prospective, Single-Center, Open-Label, Crossover Study. Lin, MR., Chang, PJ., Hsu, PC., et al.[2023]

Povidone-iodine (PI) was found to be highly effective, killing all tested bacteria immediately upon contact, making it a strong candidate for preventing infections during joint surgeries.

Chlorhexidine gluconate (CHG) and vancomycin (VANC) showed variable effectiveness, with CHG failing to kill certain bacteria at short exposure times, while VANC required longer exposure (18-20 hours) to be effective against MRSA and Staphylococcus epidermidis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Intraoperative Antiseptic Techniques in the Prevention of Periprosthetic Joint Infection: Superiority of Betadine. Cichos, KH., Andrews, RM., Wolschendorf, F., et al.[2020]

Bactisure, a recently FDA-approved topical adjuvant, showed the most significant reduction in biofilm formation of Staphylococcus aureus, Staphylococcus epidermidis, and Cutibacterium acnes on various orthopedic implant metals, indicating its potential effectiveness in treating periprosthetic joint infections.

All tested topical adjuvants, including povidone-iodine and chlorhexidine gluconate, significantly reduced biofilm formation compared to controls, demonstrating that these agents can effectively combat bacterial adherence on orthopedic implants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of topical adjuvants in reducing biofilm formation on orthopedic implants: an in vitro analysis. Kia, C., Cusano, A., Messina, J., et al.[2021]

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