Prevention of Adult Caries Study (PACS)

Prevention of Adult Caries Study

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.

Study Overview

• Status: Completed
• Conditions: Caries, Dental
• Intervention / Treatment: Other: Placebo; Drug: 10% w/v chlorhexidine acetate coating FDA IND #45466

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 983
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tuba City, Arizona, United States, 86045-0600
      • Tuba City Regional Health Care
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts University School of Dental Medicine
    • Boston, Massachusetts, United States, 02129
      • Dental Services of Massachusetts
  • Oregon
    • Portland, Oregon, United States, 97227
      • Center for Health Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Dental Coating; Dental coating with all ingredients except Chlorhexidine topically applied by dental professional supragingivally to the full dentition	Other: Placebo
Active Comparator: Active Dental Coating; 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; Dental coating topically applied by dental professional supragingivally to the full dentition; Other Names: CHX

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tufts University
• Collaborators: National Institute of Dental and Craniofacial Research (NIDCR)
• Investigators: Principal Investigator: Athena Papas, PhD DMD, Tufts University of Dental Medicine

Publications and helpful links

General Publications

• Papas AS, Vollmer WM, Gullion CM, Bader J, Laws R, Fellows J, Hollis JF, Maupome G, Singh ML, Snyder J, Blanchard P; PACS Collaborative Group. Efficacy of chlorhexidine varnish for the prevention of adult caries: a randomized trial. J Dent Res. 2012 Feb;91(2):150-5. doi: 10.1177/0022034511424154. Epub 2011 Dec 7.
• Singh M, Papas A, Vollmer W, Bader J, Laws R, Maupome G, Snyder J, Blanchard P. Predictors of coronal caries progression in adults: results from the Prevention of Adult Caries Study. Community Dent Oral Epidemiol. 2013 Dec;41(6):558-64. doi: 10.1111/cdoe.12059. Epub 2013 Jul 9.
• Banting DW, Amaechi BT, Bader JD, Blanchard P, Gilbert GH, Gullion CM, Holland JC, Makhija SK, Papas A, Ritter AV, Singh ML, Vollmer WM. Examiner training and reliability in two randomized clinical trials of adult dental caries. J Public Health Dent. 2011 Fall;71(4):335-44. doi: 10.1111/j.1752-7325.2011.00278.x. Epub 2011 Aug 17.
• Vollmer WM, Papas AS, Bader JD, Maupome G, Gullion CM, Hollis JF, Snyder JJ, Fellows JL, Laws RL, White BA; PACS Collaborative Research Group. Design of the Prevention of Adult Caries Study (PACS): a randomized clinical trial assessing the effect of a chlorhexidine dental coating for the prevention of adult caries. BMC Oral Health. 2010 Oct 5;10:23. doi: 10.1186/1472-6831-10-23.

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: July 26, 2006
• First Submitted That Met QC Criteria: July 26, 2006
• First Posted (Estimate): July 28, 2006

Study Record Updates

• Last Update Posted (Actual): June 14, 2017
• Last Update Submitted That Met QC Criteria: May 15, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Tooth Demineralization; Tooth Diseases; Dental Caries; Anti-Infective Agents, Local; Anti-Infective Agents; Dermatologic Agents; Disinfectants; Chlorhexidine; Chlorhexidine gluconate
• Other Study ID Numbers: DE017753-01; U01DE017753 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO