Povidone-Iodine for Surgical Site Infections

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Loma Linda University

Disqualifiers: Pregnancy, Iodine allergy, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a multicenter randomized controlled trial of 1100 patients to evaluate the superiority of combined intraoperative wound irrigation with intraoperative peritoneal lavage with dilute aqueous povidone-iodine compared to normal saline in male and female patients between the ages of 18 and 80 years old undergoing emergency laparotomies with Centers for Disease Control (CDC) class 2 and 3 wounds.

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 data supports the effectiveness of the treatment Povidone-Iodine for preventing surgical site infections?

Research shows that povidone-iodine is effective in reducing infections during heart surgeries and is commonly used as a skin antiseptic before surgeries, including cataract operations, due to its strong ability to kill germs. It has been found to be more effective at lower concentrations and is used to clean wounds and surgical sites to prevent infections. ^{1 2 3 4 5}

Is povidone-iodine safe for use in humans?

Povidone-iodine has been used safely for over ten years in heart surgeries for skin and wound disinfection, with minor wound healing issues in 5% of cases and more serious infections in 0.5% of cases. It is generally considered safe for local antiseptic use, but deep infections can be serious, requiring careful surgical techniques and antibiotics. ^{1 2 4 6 7}

How is the drug Povidone-Iodine unique for preventing surgical site infections?

Povidone-Iodine (Betadine) is unique because it is an antiseptic that can be used in various concentrations and forms, such as aqueous solutions, to effectively reduce bacteria on the skin and prevent infections. It is known for its excellent microbicidal activity and is less likely to cause skin irritation due to its low free iodine concentration. ^{1 3 4 8 9}

Research Team

Eligibility Criteria

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 between 18 and 80 years old.

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

Exclusion Criteria

Pregnancy

Iodine allergy

Patients unlikely to survive beyond 30 days

Trial Timeline

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

Treatment Details

Interventions

• Diluted Aqueous Povidone-Iodine (Anti-infective)

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.

Participant Groups

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 Canada, Japan, China, Switzerland for the following indications:

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+

Adrian Cotton

Loma Linda University

Chief Medical Officer since 2020

MD

Richard H. Hart

Loma Linda University

Chief Executive Officer since 2015

MD, DrPH

Findings from Research

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 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 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]

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 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Ten years experience with povidone-iodine in heart surgery. [2019]

2. United States 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. [2023]

3. England 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. [2019]

4. Switzerland 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. [2017]

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

Efficacy of povidone-iodine in pre-operative skin preparation. [2019]

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

Evaluation of the role of povidone‑iodine in the prevention of surgical site infections. [2023]

7. England pubmed.ncbi.nlm.nih.gov

The effect of diluting povidone-iodine on bacterial growth associated with speech. [2021]

8. Switzerland 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? [2022]

9. Italy 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. [2017]