Prevention of Adult Caries Study (PACS)

Study Overview
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Brief Summary
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Adult tooth decay is an infectious disease that afflicts the majority of Americans aged 55 and older and is the most common chronic disease at midlife with an ever growing economic toll. Despite the fact that specific bacteria cause tooth decay, no FDA-approved anti-microbial treatment for decay is available to the American dental professional. The Prevention of Adult Caries Study (PACS) is a study designed to evaluate the efficacy of a topical, temporary, 10% w/v chlorhexidine dental coating in reducing new decay in adult dental patients at risk for decay.

Detailed Description
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The Prevention of Adult Caries Study (PACS) is a randomized, double-blind, placebo-controlled Phase III clinical trial conducted under F.D.A. Investigational New Drug license #45,466, with a target enrollment of 1000 at four clinical centers with vastly different populations. The centers participating in this proposed research are: Kaiser Permanente's Dental Plan in Portland, Oregon; Tufts University Dental Clinic in central Boston, Massachusetts; Delta Dental Massachusetts' Dental Clinic in Southborough, Massachusetts; and the dental clinic of the Tuba City Regional Health Care Corporation in Tuba City, Arizona. Kaiser Permanente's Center for Health Research in Portland, Oregon will act as the data-coordinating center, and Tufts University will act as the Administrative Center. This study is designed to evaluate the efficacy of a topical, temporary, 10% w/v chlorhexidine dental coating in reducing caries increment in at-risk adult dental patients. This study will treat participants in months 1(4 weekly applications) and 7(1 application) with final outcome measured at 13 months after randomization. Examiners were trained and certified before data collection started and were recalibrated annually. The primary outcome analysis in the intent -to- treat sample compares active to placebo group on the rank-normalized caries increment score, adjusting for examiner, age and age squared. Multiple imputation (data augmentation using MCMC) will be used to replace missing outcome. Planned secondary analysis examine the secondary caries increment outcomes using the same model, as well as parallel analyses in the per-protocol group. Safety of the coating will be evaluated by comparing development of resistant S. mutans or C. albicans as well as incidence of MedDRA-coded adverse events between the two arms.

Official Title
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Prevention of Adult Caries Study

Conditions
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Caries, Dental

Intervention / Treatment
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* Drug: 10% w/v chlorhexidine acetate coating FDA IND #45466
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age and older at least 20 intact natural teeth, excluding third molars 2 or more lesions, of which at least one must be a cavitated D2 or D3 willing and able to provide informed consent Exclusion Criteria pregnant or planning to become pregnant or planning to become pregnant during the study (breastfeeding is permitted) use of fixed orthodontic appliances allergic to any of the ingredients of the study medication long-term antibiotic therapy a history of, or currently active, radiation therapy for cancers of the head or neck Sjögren's syndrome advanced periodontitis consumption of the equivalent of more than five servings of acidic or sugared drinks per day having 10 or more lesions requiring restorative care at the time of the screening visit remineralization therapy within one month of randomization investigator discretion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Dental Coating<br>Dental coating with all ingredients except Chlorhexidine topically applied by dental professional supragingivally to the full dentition | Other: Placebo<br> <br> |
| Active Comparator: Active Dental Coating<br>10% w/v chlorhexidine acetate coating FDA IND #45466. Dental coating with all ingredients including Chlorhexidine topically applied by dental professional supragingivally to the full dentition | Drug: 10% w/v chlorhexidine acetate coating FDA IND #45466<br>* Dental coating topically applied by dental professional supragingivally to the full dentition<br>* Other names: CHX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Net D12FS Caries Increment (Total of Non-cavitated Lesions (D1), Cavitated Lesions (D2) and Sound Surfaces (S)) | Study duration was too short to have progression from D2 (cavitated lesions) to D3 (cavitated lesions that involved dentin). D2 and D3 were treated equivalently for analysis. This measure is computed as the sum of weighted counts of transitions in tooth surface status (root and coronal surfaces combined) from randomization to the 13-month follow-up visit. Disease progression had a positive weight (e.g., S-to-D1 (sound to non-cavitated lesion) or D1-to-D2 (non-cavitated to cavitated lesion) = 1, S-to-D2 (sound to cavitated lesion)= 2). Reversal had a negative weight (e.g., D1-to-S = -1). No change, transitions to or from missing or unscorable, and impossible transitions had 0 weight. Incident fillings and crowns were treated the same as incident D2 lesions for purposes of scoring. More details of the transition weights may be found at Vollmer WM et al. (2010). Design of the Prevention of Adult Caries Study (PACS): a randomized clinical trial assessing the effect of a | (V1) to the 13 month follow-up visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Net D12FS Caries Increment | This measure was computed similar to the total net D12FS increment, but separately scored and combined transitions from the baseline to 7-month visits and from the 7- to 13-month visits, rather than simply looking at the baseline to 13-month visits. | Visit 1, 7-month follow-up, 13-month follow-up | 
| Total Crude D12FS Caries Increment | Computed analogous to the total net D12FS caries increment, but ignoring reversals (essentially assigned them zero weight). Computed only using baseline to 13-month visit data. | V1-13-month follow-up | 
| Cumulative Crude D12FS Caries Increment | This is computed analogous to the cumulative net D12FS increment, but ignoring reversals by assigning them weights of zero. | Visit 1, 7-month follow-up, 13-month follow-up |