Povidone Iodine Efficacy Study

Study Overview
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Brief Summary
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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.

Detailed Description
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Objectives: Primary: To assess the efficacy of 10% PVPI in children with S-ECC to prevent new cavitated caries lesions that require follow-up restorative/surgical intervention after oral rehabilitation in the Operating Room (OR) under general anesthesia. The primary outcome variable is time from randomization to relapse. The development of an ICDAS caries code 3 (cavitated caries lesion) or higher lesion post dental surgery is the sentinel event to calculate time to relapse. Secondary: To determine incidence and severity of dental caries following oral rehabilitation in the OR. This outcome measure will be assessed by counting non-cavitated and cavitated carious lesions and any filled (due to caries), missing (due to caries) and sealed surfaces over the 2-year study period. The International Caries Diagnostic Assessment System (ICDAS) index will be used. To determine diversity and composition of oral microbiota, including cariogenic Streptococcus Mutans, Lactobacilli and Candida species over the 2-year study period. 16S rRNA amplicon analysis of saliva from all participants will be used to identify bacterial taxa associated with dental caries. We will also quantify Colony Forming Units per mL (CFU/mL) of S. mutans, Lactobacilli and Candida species. 3. To determine the frequency of adverse event occurrence. Adverse events (AEs) will be collected from the parent/primary caregiver, as well as those observed by study investigators including unanticipated problems (UPs) and severe adverse events (SAEs) over the 2 year study period. Population: Healthy children with S-ECC 24 to 71 months of age and their parents/primary caregivers from Rochester NY and the surrounding area will be invited to participate in this study. Enrolled children will be patients of record in the Pediatric Dentistry Division of the Eastman Institute for Oral Health (EIOH), University of Rochester, who require treatment for S-ECC in the OR under general anesthesia. Phase or Stage: Phase II RCT Number of Sites: 1 site, University of Rochester Description of Intervention: The test agent will be 10% PVPI (Betadine Solution, Purdue Frederick Co., Stamford, CT). The placebo will consist of fluoride-free sterile water for injection USP and commercial powdered tea without sweetener or lemon (Lipton decaffeinated unsweetened tea, Lipton, Unilever, Englewood Cliffs, NJ) with addition of Red and Yellow Food Color (McCormick and Co., Inc., Hunt Valley, MD) to simulate the color of the 10% PVPI. After drying the teeth, up to 15 µl of 10% PVPI or placebo solution will be applied to the child's teeth with a microbrush. Following application of the test agent (PVPI or placebo), FV (Duraflor®- 5% Sodium Fluoride Varnish, Bubble gum flavor, AMD Medicom, Inc. Quebec, Canada) that is the standard of care will be applied with the manufacturer's supplied applicator.

Official Title
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Povidone Iodine Efficacy Study

Conditions
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Early Childhood Caries

Intervention / Treatment
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* Drug: 10% povidone iodine + FV
* Other: Placebo +FV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide signed and dated informed consent/permission form Parents/primary caregivers willing to comply with all study procedures and be available for the duration of the study Male or female, of any race, ethnicity, aged 24 to 71 months and their parents/primary caregivers who are 18 years of age or older or emancipated minors In good general health as evidenced by medical history, per PI, and in compliance with current CDC, NYS Department of Health and URMC COVID-19 guidelines. American Society of Anesthesiologists (ASA) categories will be used; children classified as ASA I and ASA II will be eligible for the study. Diagnosed with Severe-Early Childhood Caries (S-ECC) requiring treatment in the operating room (OR). A diagnosis of S-ECC will be based on the definition in accordance with American Academy of Pediatric Dentistry (AAPD) Exclusion Criteria: Having a known allergy or sensitivity to iodine or seafood, red or yellow food coloring, or to tea, including a hypersensitivity to fluoride varnish, or having thyroid disease, as determined by medical history Receiving or having received treatment with another investigational drug within 30 days of the baseline visit (V1)

Ages Eligible for Study
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Minimum Age: 24 Months
Maximum Age: 71 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Povidone Iodine<br>10% povidone iodine + fluoride varnish | Drug: 10% povidone iodine + FV<br>* applied to children's teeth<br>* Other names: betadine;|
| Placebo Comparator: Placebo<br>Placebo (iced tea) + fluoride varnish | Other: Placebo +FV<br>* applied to children's teeth<br>* Other names: Iced tea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Caries lesion | The primary outcome variable is time from randomization to relapse. The development of an ICDAS caries code 3 (cavitated caries lesion) or higher lesion post dental surgery is the sentinel event to calculate time to relapse. | Randomization to relapse, up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of dental caries | To determine incidence and severity of dental caries following oral rehabilitation in the OR. | Randomization to relapse, up to 24 months | 
| Diversity of oral microbiota | To determine diversity of oral microbiota, including cariogenic Streptococcus Mutans, Lactobacilli and Candida species over the 2-year study period. Concentration (CFU/ml) will be measured | Randomization to relapse, up to 24 months | 
| Adverse Event Occurrence | To determine the frequency of adverse event occurrence | Enrollment to 24 months | 
| Composition of Microbiota | To determine composition of oral microbiota, including cariogenic Streptococcus Mutans, Lactobacilli and Candida species over the 2-year study period. Presence of species (yes or no) will be measured | Randomization to relapse, up to 24 months |