Antiseptic Skin Preparation for Joint Replacement Surgery

(CLEANJoint Trial)

Recruiting at 3 trial locations

Overseen By Erin Lillie, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Disqualifiers: Prosthetic joint infection, Allergy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 1 day

400 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to compare two types of skin preparation solutions (chlorhexidine gluconate-alcohol solution and povidone-iodine solution) that help eliminate harmful bacteria on the skin at the time of surgery for patients having revision arthroplasty surgery of the hip or knee. The main outcome of interest for the definitive study is the need for re-operation for a wound complication or an infection of the prosthetic joint within one year after surgery. For the pilot trial, our main interest is to determine feasibility of a definitive trial. Feasibility outcomes will include: ability to recruit patients, ability to randomize patients, ability to collect complete data, estimate the event rate of our primary outcome, ability to carry out data linkages and determine the accuracy of collected data. Participants will be contacted at two time points after surgery to complete a 5-minute survey: after 30 days, and after 1 year.

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 focuses on skin preparation solutions for surgery.

What data supports the effectiveness of the treatment Chlorhexidine Gluconate-Alcohol Solution and Povidone-Iodine Solution for antiseptic skin preparation in joint replacement surgery?

Research shows that antiseptic solutions containing chlorhexidine gluconate and povidone iodine, especially when combined with alcohol, are effective in reducing the risk of surgical site infections by killing bacteria on the skin before surgery. These solutions are commonly used in various surgeries, including cardiac and abdominal, to prevent infections. ^{1 2 3 4 5}

Is antiseptic skin preparation safe for humans?

Antiseptic solutions like Chlorhexidine Gluconate (CHG) and Povidone-Iodine (PI) are generally safe for human use, but CHG-based solutions can cause severe eye and ear irritation, while PI solutions show minimal toxic effects on these areas. ^{3 4 6 7 8}

How does the antiseptic skin preparation treatment for joint replacement surgery differ from other treatments?

This treatment is unique because it combines chlorhexidine gluconate and povidone-iodine with alcohol, which enhances their antimicrobial effects and reduces the risk of surgical site infections more effectively than using these agents alone. ^{3 4 5 9 10}

Research Team

Raman Mundi, MD MSc FRCSC

Principal Investigator

Sunnybrook Health Sciences Centre

Eligibility Criteria

This trial is for adults aged 18 or older who are scheduled to have revision surgery on a hip or knee replacement where at least one artificial joint part will be swapped out. It's not suitable for those with conditions that might interfere with the study.

Inclusion Criteria

I am scheduled for a hip or knee replacement revision.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo revision arthroplasty surgery with either chlorhexidine gluconate-alcohol solution or povidone-iodine solution for skin preparation

1 day

1 visit (in-person)

Follow-up

Participants are monitored for re-operation, wound complications, and infection of the prosthetic joint. Surveys are conducted at 30 days and 1 year post-surgery.

1 year

2 visits (virtual or in-person)

Treatment Details

Interventions

• Chlorhexidine Gluconate-Alcohol Solution
• Povidone-Iodine Solution

Trial Overview The study compares two antiseptic solutions used during surgery: chlorhexidine gluconate-alcohol and povidone-iodine, to see which is better at preventing infections after hip or knee replacement revisions. Participants will be randomly assigned to a solution and surveyed twice post-surgery.

Participant Groups

Group I: Chlorhexidine gluconate-alcohol solution Active Control 1 Intervention

Chlorhexidine gluconate-alcohol solution is a type of solution that has antiseptic properties, which means it helps to eliminate harmful bacteria on the skin at the time of surgery, and therefore, reduce the risk of infection.

Group II: Povidone-iodine solution Active Control 1 Intervention

Povidone-iodine solution is a type of solution that has antiseptic properties, which means it helps to eliminate harmful bacteria on the skin at the time of surgery, and therefore, reduce the risk of infection.

Chlorhexidine Gluconate-Alcohol Solution is already approved in European Union, United States, Canada, Switzerland for the following indications:

Approved in European Union as Chlorhexidine Gluconate-Alcohol Solution for:

• Surgical skin preparation
• Prevention of surgical site infections

Approved in United States as Chlorhexidine Gluconate-Alcohol Solution for:

• Surgical skin preparation
• Prevention of surgical site infections

Approved in Canada as Chlorhexidine Gluconate-Alcohol Solution for:

• Surgical skin preparation
• Prevention of surgical site infections

Approved in Switzerland as Chlorhexidine Gluconate-Alcohol Solution for:

• Surgical skin preparation
• Prevention of surgical site infections

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Findings from Research

Both Povidone iodine with isopropyl alcohol (PVP-I+IPA) and Iodine Povacrylex+IPA showed strong antimicrobial activity, effectively reducing microbial populations by 99.99% in time-kill tests at various contact times, indicating their efficacy in preventing healthcare-associated infections.

In a clinical study, both antiseptic solutions met FDA efficacy requirements for antimicrobial activity on skin, demonstrating safety with no adverse events, thus supporting their use in preoperative skin preparation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobial performance of two preoperative skin preparation solutions containing iodine and isopropyl alcohol. Bashir, MH., Hollingsworth, A., Thompson, JD., et al.[2022]

A meta-analysis of 11 randomized controlled trials involving 12,072 participants found that alcohol-based chlorhexidine gluconate (CHG) significantly reduces the risk of surgical site infections (SSIs) compared to aqueous-based povidone-iodine (PVI) in abdominal surgeries, with an odds ratio of 0.84.

The findings suggest that using alcohol-based CHG as a skin antiseptic before abdominal surgery may be more effective in preventing SSIs, potentially influencing clinical practice guidelines for surgical preparations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alcohol-Containing Versus Aqueous-Based Solutions for Skin Preparation in Abdominal Surgery: A Systematic Review and Meta-analysis. Peristeri, DV., Nour, HM., Ahsan, A., et al.[2023]

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 of 1,476 cardiac surgery patients, both 2% chlorhexidine-alcohol and 10% povidone-iodine-alcohol skin preparations showed similar overall rates of surgical site infections (SSI), with rates of 3.3% and 3.8% respectively.

However, the 10% povidone-iodine-alcohol preparation was found to be marginally more effective in reducing organ-space infections, suggesting it may offer a slight advantage in that specific area without significantly improving the prevention of incisional SSIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of choice of skin preparation solution in cardiac surgery on rate of surgical site infection: a propensity score matched analysis. Raja, SG., Rochon, M., Mullins, C., et al.[2022]

This pilot study successfully demonstrated the feasibility of a cluster randomized crossover trial to compare the effectiveness of 10% povidone-iodine and 4% chlorhexidine gluconate solutions in preventing surgical site infections in orthopedic trauma patients.

Out of 135 enrolled patients, the study achieved a high compliance rate of 98% and 100% accurate documentation of surgical site infections, indicating that the trial design is robust and ready for a definitive study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pragmatic randomized trial evaluating pre-operative aqueous antiseptic skin solution in open fractures (Aqueous-PREP): the feasibility of a cluster randomized crossover study. Sprague, S., Guyatt, P., Bzovsky, S., et al.[2021]

Chlorhexidine Gluconate (CHG) and its derivatives can cause severe eye and ear damage, even with minimal exposure during surgical preparations, leading to serious conditions like corneal injury and potential blindness.

In contrast, 10% Povidone-Iodine (PI) solutions show minimal toxicity to the eyes and ears while providing similar effectiveness in preventing surgical site infections, making them a safer alternative for preoperative skin preparation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review: Perspective on ocular toxicity of presurgical skin preparations utilizing Chlorhexidine Gluconate/Hibiclens/Chloraprep. Epstein, NE.[2022]

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]

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]

In a study of 351 patients undergoing clean-contaminated upper abdominal surgeries, chlorhexidine-gluconate skin preparation resulted in a lower incidence of surgical site infections (SSIs) at 10.8% compared to 17.9% for povidone iodine, suggesting it may be a more effective option.

While the overall results were not statistically significant, chlorhexidine showed a significant reduction in SSIs during the first postoperative week (7% vs. 14.1% for povidone iodine, P = 0.03), indicating a potential benefit in early postoperative infection prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy of chlorhexidine gluconate versus povidone iodine as preoperative skin preparation for the prevention of surgical site infections in clean-contaminated upper abdominal surgeries. Srinivas, A., Kaman, L., Raj, P., et al.[2018]

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]

References

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

Antimicrobial performance of two preoperative skin preparation solutions containing iodine and isopropyl alcohol. [2022]

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

Alcohol-Containing Versus Aqueous-Based Solutions for Skin Preparation in Abdominal Surgery: A Systematic Review and Meta-analysis. [2023]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Impact of choice of skin preparation solution in cardiac surgery on rate of surgical site infection: a propensity score matched analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Pragmatic randomized trial evaluating pre-operative aqueous antiseptic skin solution in open fractures (Aqueous-PREP): the feasibility of a cluster randomized crossover study. [2021]

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

Review: Perspective on ocular toxicity of presurgical skin preparations utilizing Chlorhexidine Gluconate/Hibiclens/Chloraprep. [2022]

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

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

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

Comparison of the efficacy of chlorhexidine gluconate versus povidone iodine as preoperative skin preparation for the prevention of surgical site infections in clean-contaminated upper abdominal surgeries. [2018]

10. 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]