Povidone-Iodine for Surgical Site Infections

Overseen By Mohamed H El-Farra, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Loma Linda University

Disqualifiers: Pregnancy, Iodine allergy, 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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Intraoperative

1100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a diluted povidone-iodine solution during surgery can better prevent infections compared to regular saline for individuals undergoing emergency abdominal surgeries. Researchers aim to determine if this iodine solution helps keep wounds cleaner and reduces surgical site infections. Those who have had abdominal surgery with a wound classified as CDC class 2 or 3 might find this trial relevant. Participants must not have pre-existing infections or an allergy to iodine. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

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

Research has shown that povidone-iodine is generally safe for cleaning the skin before surgery. Studies indicate that using povidone-iodine during surgery results in low infection rates, demonstrating its safety. Some studies even suggest using it to wash out wounds, as it helps lower infection risk.

Although povidone-iodine is not as effective as some other solutions, such as chlorhexidine, in preventing infections, it remains widely used and considered safe for surgical wound care. Studies have reported no major safety issues, indicating its safety for human use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using povidone-iodine for surgical site infections because it offers a unique approach to preventing these infections. Unlike standard treatments that often rely on antibiotics, povidone-iodine is an antiseptic solution that directly kills bacteria on contact, potentially reducing antibiotic use and resistance. Additionally, this treatment involves intraoperative peritoneal lavage and wound irrigation, which could enhance its effectiveness by thoroughly cleansing the surgical site during the procedure. By exploring this method, researchers hope to find a more effective way to prevent infections without contributing to the growing problem of antibiotic resistance.

What evidence suggests that diluted aqueous povidone-iodine is effective for surgical site infections?

This trial will compare the effectiveness of povidone-iodine and normal saline in preventing surgical site infections. Studies have shown that cleaning surgical areas with povidone-iodine can help prevent post-surgery infections. Specifically, preparing the surgical site with povidone-iodine reduces the risk of these infections. Research supports its use for washing wounds during surgery to lower infection rates, particularly in surgeries involving the stomach and intestines. Overall, povidone-iodine offers a simple and affordable method to help keep surgical wounds free from infection. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-80 who are undergoing emergency abdominal surgery (laparotomies) with a moderate to high risk of infection. Participants must have wounds classified as CDC class 2 or 3, indicating some degree of contamination.

Inclusion Criteria

I am having surgery to explore a moderately or severely infected wound.

Exclusion Criteria

Pregnancy

Iodine allergy

Patients unlikely to survive beyond 30 days

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo intraoperative peritoneal lavage and wound irrigation with either diluted aqueous povidone-iodine or normal saline during emergency laparotomies

Intraoperative

Follow-up

Participants are monitored for safety and effectiveness, including surgical site infections, readmissions, and other complications

30 days

Post-operative follow-up visits

Long-term follow-up

Subjects are followed over 18 months to assess long-term outcomes and safety

18 months

What Are the Treatments Tested in This Trial?

Interventions

• Diluted Aqueous Povidone-Iodine

Trial Overview The study is testing if washing out the surgical area with diluted povidone-iodine solution is better at preventing infections than using normal saline. It's a large study involving multiple centers where patients are randomly chosen to receive one treatment or the other.

How Is the Trial Designed?

Group I: Povidone-Iodine Intraoperative Peritoneal Lavage and Intraoperative Wound Irrigation Experimental Treatment 1 Intervention

Patients in this arm will undergo combined intraoperative peritoneal lavage and intraoperative wound irrigation with a diluted aqueous povidone-iodine solution.

Group II: Normal Saline Intraoperative Peritoneal Lavage and Intraoperative Wound Irrigation Active Control 1 Intervention

Patients in this arm will undergo combined intraoperative peritoneal lavage and intraoperative wound irrigation with a normal saline solution.

Diluted Aqueous Povidone-Iodine is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Betadine for:

• Preoperative skin preparation
• Surgical site infection prevention

Approved in United States as Betadine for:

• Preoperative skin preparation
• Surgical site infection prevention

Approved in Canada as Betadine for:

• Preoperative skin preparation
• Surgical site infection prevention

Approved in Japan as Betadine for:

• Preoperative skin preparation
• Surgical site infection prevention

Approved in China as Betadine for:

• Preoperative skin preparation
• Surgical site infection prevention

Approved in Switzerland as Betadine for:

• Preoperative skin preparation
• Surgical site infection prevention

Who Is Running the Clinical Trial?

Loma Linda University

Lead Sponsor

Trials

322

Recruited

267,000+

Published Research Related to This Trial

In a study of 7566 patients undergoing open-heart surgery, the use of 10% povidone-iodine (PVP-I) for skin and wound disinfection resulted in a low incidence of severe infections, with only 0.5% experiencing deep sternal or retrosternal infections.

While superficial wound healing defects occurred in 5% of patients and were easily treatable with local PVP-I application, deep infections posed a significant risk, leading to a 40% mortality rate, highlighting the importance of strict aseptic techniques and effective antibiotic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ten years experience with povidone-iodine in heart surgery. Klövekorn, WP., Meisner, H., Sebening, F.[2019]

In a study involving 105 patients undergoing cataract surgery, 5% povidone-iodine (PI) was found to be significantly more effective than 1% PI in reducing bacterial colonies on the conjunctiva, especially when initial bacterial loads were high.

While in vitro studies suggested that lower concentrations of PI might be more effective, this in vivo study demonstrated that 5% PI resulted in a greater reduction in bacterial counts, indicating its superior efficacy as a preoperative antiseptic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of 5% povidone-iodine solution against 1% povidone-iodine solution in preoperative cataract surgery antisepsis: a prospective randomised double blind study. Ferguson, AW., Scott, JA., McGavigan, J., et al.[2019]

In a study involving 941 patients undergoing gastroenterological surgery, intraoperative wound irrigation (IOWI) with aqueous povidone-iodine (PVP-I) did not significantly reduce the incidence of surgical site infections (SSI) compared to saline, with SSI rates of 7.6% for PVP-I and 5.1% for saline.

The results suggest that the current recommendation for using IOWI with PVP-I for preventing SSIs may need to be reevaluated, as the difference in infection rates was not statistically significant (P = 0.154).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aqueous Povidone-Iodine Versus Normal Saline For Intraoperative Wound Irrigation on The Incidence of Surgical Site Infection in Clean-Contaminated Wounds After Gastroenterological Surgery: A Single-Institute, Prospective, Blinded-Endpoint, Randomized Controlled Trial. Maemoto, R., Noda, H., Ichida, K., et al.[2023]

In a study involving 21 participants, it was found that only 5% povidone-iodine (PI) significantly reduced bacterial growth from droplet dispersal during speech, with a median of 2 CFUs compared to 25 CFUs in the control group.

Lower concentrations of PI (1% and 2.5%) did not effectively decrease bacterial growth, indicating that for antiseptic use prior to intravitreal injections, a concentration of at least 5% should be used to ensure safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of diluting povidone-iodine on bacterial growth associated with speech. Gnanasekaran, S., Rogers, S., Wickremasinghe, S., et al.[2021]

Povidone iodine (PVP-I) is widely used as a pre-operative antiseptic, but there are rare cases of allergic reactions, as demonstrated in two patients who developed allergic contact dermatitis after its use.

While PVP-I is generally considered a low sensitizer, this case highlights the need for further evaluation of its potential to cause allergic reactions, suggesting that pre-operative allergy testing for PVP-I may be worth considering in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An unusual complication of late onset allergic contact dermatitis to povidone iodine in oral & maxillofacial surgery - a report of 2 cases. Reyazulla, MA., Gopinath, AL., Vaibhav, N., et al.[2017]

Povidone-iodine (PVP-I) is shown to be an effective antibacterial agent for preparing skin before surgical operations, based on cultures of microbial flora taken from the operation site.

The study involved comparing microbial cultures obtained pre-operatively and after the application of PVP-I, indicating its efficacy in reducing skin bacteria before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of povidone-iodine in pre-operative skin preparation. Georgiade, G., Riefkohl, R., Georgiade, N., et al.[2019]

The study found that while 10% Betadine solution effectively inhibited the growth of Staphylococcus aureus, it did not completely kill other tested bacteria, including Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter baumannii.

The research highlighted that using only the zone of inhibition assay is insufficient for assessing antimicrobial effectiveness; a colony-forming unit assay is necessary for a more accurate evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An in vitro Study of Betadine's Ability to Eliminate Live Bacteria on the Eye: Should It Be Used for Protection against Endophthalmitis? Nagle, A., Kopel, J., Reed, J., et al.[2022]

Liposomal formulations of povidone-iodine (PVP-I) are significantly less toxic to blood vessels compared to traditional aqueous PVP-I formulations, as demonstrated in a study using chick embryo models.

The study showed that liposomal PVP-I formulations reduced angiotoxic effects, such as coagulation and hemorrhages, indicating a safer option for local anti-infective treatments, especially in wound care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative testing of liposomal and aqueous formulations of povidone-iodine for their angioirritative potential at the chorioallantoic membrane of ex ovo cultivated chick embryos. Wutzler, P., Sauerbrei, A., Härtl, A., et al.[2017]

Povidone-iodine (PVP-I) is effective in reducing surgical site infections (SSIs) when used at all stages of surgical intervention, including preoperative skin preparation, intraoperative irrigation, and postoperative wound management.

The review highlights the need for more rigorous clinical trials to compare PVP-I with other antiseptic agents, particularly for preoperative use, to better understand its advantages and potential economic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the role of povidone‑iodine in the prevention of surgical site infections. Monstrey, SJ., Govaers, K., Lejuste, P., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2386220/

The efficacy and risks of using povidone-iodine irrigation to ... Conclusion. Povidone-iodine irrigation is a simple and inexpensive solution with the potential to prevent surgical site infection.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2589845023000118

Evaluation of the role of povidone‑iodine in the prevention ... Surgical site preparation with PVP-I leads to low surgical site infection (SSI) rates. •. PVP-I is recommended for intraoperative irrigation and decreases SSIs.

3. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2817941

Incisional Wound Irrigation for the Prevention of Surgical ... Incisional wound irrigation with aqueous antiseptic solutions was associated with a reduction in the risk of SSIs; results suggest that the use of antibiotic ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0039606024002861

Effects of povidone-iodine wound irrigation on surgical site ... This study examined the irrigation efficacy of povidone-iodine for surgical site infection prevention compared to control in gastroenterological surgery.

5. healthcare-bulletin.co.uk healthcare-bulletin.co.uk/article/preoperative-skin-antisepsis-with-povidone-iodine-versus-chlorhexidine-a-prospective-comparative-study-on-surgical-site-infection-prevention-4000/

Preoperative Skin Antisepsis with Povidone-Iodine versus ... Conclusion: Chlorhexidine-based skin preparation significantly reduced SSI rates compared to povidone-iodine, particularly in clean-contaminated ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa0810988

Chlorhexidine–Alcohol versus Povidone–Iodine for ... In this randomized study, the application of chlorhexidine–alcohol reduced the risk of surgical-site infection by 41% as compared with the most ...