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

Trial Summary

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.

What data supports the effectiveness of the treatment Chlorhexidine Gluconate, Betasept, Biopatch, Calgon Vesta, ChloraPrep One-Step, Dyna-Hex, Hibiclens, Hibistat Towelette, Scrub Care Exidine, Spectrum-4, Dentohexin, Paroex, Peridex, PerioChip, Corsodyl, Periogard, Povidone-Iodine, Betadine, PVP-I, Vancomycin Hydrochloride, Vancomycin HCl, Vancocin for infection prophylaxis in joint replacement?

Research shows that chlorhexidine gluconate and povidone-iodine are effective in reducing bacteria and preventing infections, such as in surgical settings and catheter-related bloodstream infections. Chlorhexidine was found to reduce bacterial counts more effectively than povidone-iodine in surgical scrubs, and both agents are commonly used to prevent infections in joint replacement surgeries. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Research shows that chlorhexidine gluconate (CHG) and povidone-iodine (PVI) are commonly used antiseptics for skin preparation before surgery and are generally considered safe for human use. Studies have compared their antimicrobial effectiveness and safety, indicating they are effective in reducing bacteria on the skin without significant safety concerns. ^{1 2 5 6 7}

How does the treatment for infection prophylaxis in joint replacement differ from other treatments?

This treatment is unique because it involves the use of antiseptic techniques like povidone-iodine (Betadine) and chlorhexidine gluconate (CHG) to prevent infections during joint replacement surgery. These antiseptics are applied directly to the surgical site to reduce bacteria and prevent infections, which is different from systemic antibiotics that are taken orally or injected. ^{1 2 3 4 8}

What is the purpose of this trial?

Osteoarthritis (OA) is the most common cause of disability in older adults worldwide affecting 7% of the global population, or more than 500 million people globally. Total joint replacements (TJR) can help bring relief to those with osteoarthritis when other treatment options are no longer helpful. Infection is the main reason hip and knee replacements "fail". Failure leads to repeat surgeries that are often more complicated and less likely to be successful than the first surgery. Reducing the risk of infection is extremely important, antiseptic washes and antibiotics may help us do that. After joint replacement surgery, orthopaedic surgeons wash and clean the surgical wound to lower the risk of infection. The goal of this clinical trial is to determine if the use of antiseptic solutions to wash the surgical site and placing an antibiotic directly into the wound will reduce the number of infections requiring reoperation. Patients having total joint replacements will be randomized (like flipping a coin) to receive 6 possible combinations of washes and / or antibiotics. Participants will be followed for one year after TJR to compare the rate of infection in each group.

Research Team

Thomas J Wood, MD, FRCSC

Principal Investigator

Hamilton Health Sciences / McMaster University

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Efficacy of Intraoperative Antiseptic Techniques in the Prevention of Periprosthetic Joint Infection: Superiority of Betadine. [2020]

2. France pubmed.ncbi.nlm.nih.gov

Surgical solutions for preoperative skin preparation in total hip arthroplasty: A cost-effectiveness analysis of Betadine® and Chloraprep™. [2022]

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

Effectiveness of topical adjuvants in reducing biofilm formation on orthopedic implants: an in vitro analysis. [2021]

4. Switzerland 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. [2023]

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

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

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

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

7. Korea (South) pubmed.ncbi.nlm.nih.gov

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

8. United States 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. [2022]