Povidone Iodine + Fluoride Varnish for Early Childhood Caries

(PIES Trial)

Overseen By Dorota T Kopycka-Kedzierawski, DDS, MPH

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Rochester

Disqualifiers: Iodine allergy, Thyroid disease, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 24 months

246 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single center, randomized, double-blind, placebo-controlled Phase II clinical trial (RCT) to evaluate the efficacy of topical 10% Polyvinylpyrrolidone-Iodine (PVPI) to prevent new cavitated caries lesions when applied to the teeth of children with Severe Early Childhood Caries (S-ECC). At baseline, following oral rehabilitation in the operating room {10% (PVPI + Fluoride Varnish (FV)} will be compared to the current standard of care (Placebo + FV). Study participants will be followed for approximately 24 months post-baseline. The study interventions post-baseline will be administered at 3, 6, 9, 12, 15, 18, and 21 months.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications. However, if you are receiving or have received another investigational drug within 30 days of the baseline visit, you may not be eligible to participate.

What data supports the effectiveness of the treatment Povidone Iodine + Fluoride Varnish for Early Childhood Caries?

Povidone-iodine is known for its strong ability to kill germs and is used in various forms to prevent infections, as shown in studies where it effectively reduced bacteria and promoted healing in wounds. This suggests it could be beneficial in treating early childhood caries by reducing harmful bacteria in the mouth. ^{1 2 3 4 5}

Is Povidone Iodine safe for use in humans?

Povidone Iodine is generally considered safe for use in humans, with low potential for skin irritation and adverse reactions. However, rare allergic reactions can occur, and it is less irritating than other iodine solutions due to its low free iodine concentration. ^{1 2 3 4 6}

How does the Povidone Iodine + Fluoride Varnish treatment for early childhood caries differ from other treatments?

This treatment combines povidone iodine, a broad-spectrum antiseptic, with fluoride, which helps strengthen tooth enamel, to potentially offer a more effective approach than fluoride alone in preventing dental caries. The combination is designed to reduce harmful bacteria while promoting enamel remineralization, and it has been shown to be well tolerated with minimal absorption into the body. ^{1 2 4 7 8}

Research Team

Dorota T Kopycka-Kedzierawski, DDS, MPH

Principal Investigator

University of Rochester

Eligibility Criteria

This trial is for children aged 24 to 71 months with severe early childhood caries needing treatment in the operating room. It's open to kids in good health and ASA I or II categories. Parents must consent, follow study procedures, and adhere to COVID-19 guidelines. Kids with iodine or seafood allergies, sensitivity to certain food colorings or tea, recent investigational drug use, or thyroid disease can't participate.

Inclusion Criteria

Provide signed and dated informed consent/permission form

My child has severe early tooth decay needing treatment in an OR, as defined by the AAPD.

I am between 2 and almost 6 years old, or I am the adult caregiver of someone in that age range.

Exclusion Criteria

You have allergies to iodine, seafood, red or yellow food coloring, or tea. You also have a history of thyroid disease or are hypersensitive to fluoride varnish.

You cannot have taken any other experimental drugs within the month leading up to the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 10% PVPI or placebo applied to their teeth, followed by fluoride varnish, at baseline and at 3, 6, 9, 12, 15, 18, and 21 months

24 months

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of caries lesions and oral microbiota

24 months

Treatment Details

Interventions

• 10% Povidone Iodine

Trial Overview The trial tests if applying a topical solution of 10% povidone iodine plus fluoride varnish (PVPI + FV) prevents new cavities better than placebo plus fluoride varnish (Placebo + FV). Children will be randomly assigned treatments and followed for about two years with applications at several intervals post-baseline.

Participant Groups

Group I: Povidone Iodine Experimental Treatment 1 Intervention

10% povidone iodine + fluoride varnish

Group II: Placebo Placebo Group 1 Intervention

Placebo (iced tea) + fluoride varnish

10% Povidone Iodine is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Betadine for:

• Wound care
• Skin disinfection
• Oral care
• Preoperative skin preparation

Approved in European Union as Povidone-Iodine for:

• Wound care
• Skin disinfection
• Oral care
• Preoperative skin preparation
• Periodontal pocket disinfection

Approved in Canada as Povidone-Iodine for:

• Wound care
• Skin disinfection
• Oral care
• Preoperative skin preparation

Approved in Japan as Povidone-Iodine for:

• Wound care
• Skin disinfection
• Oral care
• Preoperative skin preparation

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Findings from Research

In a study involving 16 adults with periodontitis, subgingival irrigation with 10% PVP-iodine combined with scaling and root planing led to a significant 95% reduction in total pathogen counts in 44% of deep periodontal pockets, compared to only 6-13% reduction with other treatments.

The addition of PVP-iodine irrigation to mechanical therapy also resulted in a greater reduction in probing pocket depth (1.8 mm) compared to PVP-iodine alone (0.9 mm) or saline (0.9 mm), suggesting that PVP-iodine is most effective when used alongside traditional periodontal treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Povidone-iodine as a periodontal pocket disinfectant. Hoang, T., Jorgensen, MG., Keim, RG., 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 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]

A 5% povidone-iodine cream (PVP-I) demonstrated rapid antimicrobial activity, effectively killing a range of bacteria within 60 seconds, compared to over 15 minutes for a combination-antibiotic cream (Neosporin).

In clinical trials involving standardized wounds infected with Staphylococcus aureus, PVP-I cream showed significant reductions in bacterial counts and faster healing compared to no treatment, with minimal irritation reported during application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The comparative efficacy and safety of 5% povidone-iodine cream for topical antisepsis. Stahl-Bayliss, CM., Grandy, RP., Fitzmartin, RD., et al.[2017]

A case report of a 13-year-old patient revealed that daily disinfection of fasciotomy wounds with povidone-iodine (PVP-I) may have led to iodide absorption, contributing to hypothyroidism and prolonged kidney injury after severe abdominal sepsis.

After stopping PVP-I exposure and starting thyroid hormone treatment, the patient's kidney function improved, suggesting that PVP-I toxicity and/or hypothyroidism could have played a role in the persistent renal failure, highlighting the need for careful monitoring of PVP-I use in critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Povidone Iodine Disinfection Associated with Hypothyroidism and Potentially Contributing to Prolonged Kidney Failure. Vercammen, Y., Dauwe, D., De Vlieger, G., et al.[2022]

A 9-year-old boy with suspected PVP-I allergy experienced anaphylaxis after using a PVP-I solution, but skin prick tests were negative, highlighting the challenge in diagnosing PVP allergies.

The histamine release test (HRT) proved useful in confirming the allergy, as it showed histamine release when basophils were exposed to PVP in the presence of serum, suggesting that negative skin tests do not completely rule out PVP allergy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anaphylaxis to polyvinylpyrrolidone in povidone-iodine for impetigo contagiosum in a boy with atopic dermatitis. Yoshida, K., Sakurai, Y., Kawahara, S., et al.[2017]

The combination of 10% povidone iodine (PVP-I) and 5% sodium fluoride (NaF) in a dental varnish was well tolerated by 16 healthy adult participants, with no adverse events reported, indicating its safety for use.

After application, serum levels of iodine and fluoride increased temporarily but remained within normal ranges after 24 hours, suggesting effective but controlled absorption of the active ingredients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Iodine and Fluoride following Application of an Anticaries Varnish in Adults. Lin, YS., Rothen, ML., Milgrom, P.[2020]

Short exposure to povidone-iodine (PVP-I) at concentrations of 1:10 and higher significantly decreased osteoblast viability and differentiation, but lower dilutions (1:1000) allowed for recovery in cell proliferation.

The presence of bone-morphogenetic protein-2 (BMP-2) helped restore alkaline phosphatase activity to near control levels, and even undiluted PVP-I showed increased mineral deposition, indicating potential for enhanced bone formation despite initial toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of short-time povidone-iodine application on osteoblast proliferation and differentiation. Schmidlin, PR., Imfeld, T., Sahrmann, P., et al.[2021]

References

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

Povidone-iodine as a periodontal pocket disinfectant. [2019]

2. 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]

3. 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]

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

The comparative efficacy and safety of 5% povidone-iodine cream for topical antisepsis. [2017]

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

Povidone Iodine Disinfection Associated with Hypothyroidism and Potentially Contributing to Prolonged Kidney Failure. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Anaphylaxis to polyvinylpyrrolidone in povidone-iodine for impetigo contagiosum in a boy with atopic dermatitis. [2017]

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

Pharmacokinetics of Iodine and Fluoride following Application of an Anticaries Varnish in Adults. [2020]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Effect of short-time povidone-iodine application on osteoblast proliferation and differentiation. [2021]