Mechanical methods of dental plaque removal have existed for centuries. Nearly a century ago, the ADA recommended the mechanical oral care regimen of twice daily toothbrushing and daily interdental cleaning (for example, flossing).1 To this day, this regimen is regarded widely as being a highly effective means of helping control dental caries and periodontal disease, both of which are plaque-mediated conditions and rank among the most common diseases in humans.2 For a variety of reasons, however, this mechanical routine does not appear to be enough for the majority of people, as supported by incidence and prevalence data. For example, gingivitis was present in 63 percent of the adult U.S. population sampled in the Third National Health and Nutrition Examination Survey.3
Mechanical methods of oral hygiene can be complemented by the use of chemotherapeutic mouthrinses.
About three decades ago, researchers suggested that adding chemotherapeutic agents to the mechanical regimen may help control plaque and gingivitis, the earliest form of periodontal disease.4,5 Only two mouthrinse formulations—an essential oil–, or EO–, containing mouthrinse and a .12 percent chlorhexidine mouthrinse—have been awarded the ADA’s Council on Scientific Affairs Seal of Acceptance as adjuncts for the prevention and reduction of gingivitis and plaque.6 Listerine Antiseptic Mouthrinse (Pfizer, Morris Plains, N.J.), available as an over-the-counter product, and Peridex (Zila Pharmaceuticals, Phoenix), available by prescription only, are the only mouthrinses that have fulfilled the ADA Acceptance program criteria, including being clinically proven to provide an average reduction in gingivitis of at least 20 percent in two randomized, controlled, six-month studies. We are unaware of any private-label EO–containing mouthrinses that have demonstrated clinical efficacy.
Before the baseline examination, the subjects refrained from conducting oral hygiene for at least eight hours, but no more than 18 hours.
A number of long-term studies (that is, six months or longer) of several flavors of Listerine fulfill the ADA’s criteria and have demonstrated the adjunctive benefit of Listerine in a usual home care routine.7–12 In other words, these studies were designed specifically to allow the subjects to continue with their existing mechanical regimen, which may have included flossing. Two more long-term studies were conducted recently to establish a benchmark of rinsing to flossing.13,14 Both studies demonstrated that twice daily use of Listerine is at least as good as daily flossing in reducing gingival inflammation in interproximal areas. These studies were comparative by design and never were intended to suggest that rinsing with Listerine is a viable alternative to flossing. Instead, we suggest that chemotherapeutic mouthrinses are an effective complement to mechanical oral care practices.
As a means of building on this body of evidence, we sought to determine the incremental benefit of the adjunctive use of an EO–containing antiseptic mouthrinse (Cool Mint Listerine Antiseptic, Pfizer) to routine brushing and flossing in inhibiting whole-mouth plaque and gingivitis.
 |
MATERIALS AND METHODS
|
|---|
We designed a randomized, controlled, observer-blind, parallel-group, six-month clinical trial. The design, execution and analysis of this study were in accordance with ADA Acceptance Program Guidelines on Chemotherapeutic Products for Control of Gingivitis6 and standard operating procedures for Pfizer, which comply with International Conference on Harmonisation Good Clinical Practice guidelines.15 This international standard for pharmaceutical clinical trials ensures credible and accurate data and results management.
Our clinical protocol, including informed consent, was reviewed and approved by the BioSci Research Canada (Mississauga, Ontario) institutional review board. All subjects read and signed informed consent forms before the start of the study.
We enrolled 246 healthy subjects with mild-to-moderate gingivitis. All subjects were required to have a mean Modified Gingival Index,16 or MGI, score of 
1.75 and mean plaque index, or PI, score of 1.95 at baseline to qualify for the study.
Before the baseline examination, the subjects refrained from conducting oral hygiene for at least eight hours, but no more than 18 hours. The oral examination included hard- and soft-tissue assessment and scoring of clinical indexes. We assessed gingivitis using the MGI on all scorable teeth at four areas, the buccal and lingual marginal gingivae and the interdental papillae, as
- – 0 = normal (absence of inflammation);
- – 1 = mild inflammation (slight change in color, little change in texture) of any portion of the gingival area;
- – 2 = mild inflammation of the entire gingival area;
- – 3 = moderate inflammation (moderate glazing, redness, edema and/or hypertrophy) of the gingival area;
- – 4 = severe inflammation (marked redness and edema/hypertrophy, spontaneous bleeding or ulceration) of the gingival area.
We assessed bleeding according to the gingival bleeding index,17 or BI, by inserting a periodontal probe into the gingival crevice and sweeping from the distal aspect to the mesial aspect around the tooth at a depth of approximately 1 millimeter and at an angle of approximately 60 degrees while in contact with the sulcular epithelium. We assessed each of four gingival areas—distobuccal, midbuccal, mesiolingual and midlingual—around each tooth in this manner and waited approximately 30 seconds before recording the number of gingival areas that bled, using the following scale: absence of bleeding after 30 seconds (0); bleeding observed after 30 seconds (1); immediate bleeding observed (2).
After using a disclosing solution on the teeth, we scored the plaque area using the Turesky modification of the Quigley-Hein Plaque Index18 on six surfaces of all scorable teeth as follows: no plaque (0); separate flecks or discontinuous band of plaque at the gingival (cervical) margin (1); thin (up to 1 mm), continuous band of plaque at the gingival margin (2); band of plaque wider than 1 mm but less than one-third of surface (3); plaque covering one-third or more, but less than two-thirds, of surface (4); plaque covering two-thirds or more of surface (5).
The control mouthrinse was necessary to account for any potential benefit derived from the mechanical action of rinsing itself.
After the baseline examinations, we randomly assigned subjects to one of three groups. Each subject then received a complete dental prophylaxis to remove plaque, stain and calculus, which was confirmed by the use of disclosing solution. The brushing and rinsing with a control mouthrinse, or BC, group served as the negative control group. This group was instructed to brush twice daily with an ADA-Accepted toothbrush (Oral-B 35, Gillette, Boston) and dentifrice (Colgate MFP, Colgate-Palmolive, New York), as well as to rinse twice daily with a 5 percent hydroalcohol control mouthrinse. The control mouthrinse was necessary to account for any potential benefit derived from the mechanical action of rinsing itself. We gave the brushing, flossing and rinsing with a control mouthrinse, or BFC, group the same instructions as the BC group, and we instructed them to floss (Reach Waxed Dental Floss, Johnson & Johnson, Skillman, N.J.) once daily. We instructed the brushing, flossing and rinsing with an EO–containing mouthrinse, or BFEO, group to brush and floss as the subjects in the BFC group, but to rinse with Cool Mint Listerine Antiseptic.
A dental hygienist gave flossing demonstrations and provided written instructions to subjects in the two flossing groups. We did not supervise daily oral hygiene procedures, with the exception of the initial visit. However, we required subjects to demonstrate the proper flossing technique before participating in the unsupervised portion of the study. We instructed all subjects to brush thoroughly twice daily and gave them toothbrushes and dentifrice as needed. We told all subjects to rinse twice daily for 30 seconds with 20 milliliters of their assigned rinse, and we provided 1-ounce plastic dosage cups with the 20-mL level marked. We instructed subjects to separate the two daily rinses by at least four hours. We allowed the subjects to follow their usual dietary habits, but we instructed them to refrain from using any oral care products other than what we provided to them for the study. We permitted limited interdental cleaning in all groups in instances of considerable food entrapment. We asked subjects to record rinsing and flossing use in diaries provided by BioSci Research Canada (the test site) staff members.
Subjects returned to the test site at monthly intervals for compliance evaluations, to have their test materials replenished and for adverse event monitoring. We reviewed their diaries to determine compliance, and we weighed their floss and mouthrinse containers to help us determine usage.
A trained and calibrated dental examiner (N.S.) performed all of the study examinations. To minimize bias, the examiner did not have access to any case report forms until the examinations were completed. In addition, he did not know which of the regimens had been followed. The subject, the examiner and the recorder did not have access to the treatment code. Before the three- and six-month examinations, subjects refrained from using all test products for at least four hours before the examination. To minimize potential bias, study personnel at the test site who dispensed the test products or supervised their use did not participate in the examination of subjects.
Statistical methods and data management.
We determined that a total sample size of 228 evaluable subjects (76 per treatment group) was necessary to detect the effectiveness of treatment differences between groups. This was based on the estimate of standard deviation from one of our previous studies.13 This sample size provided at least 90 percent power to detect a difference of 0.085 for MGI and 0.36 for PI, assuming a standard deviation of 0.160 for MGI and 0.367 for PI. We used SAS Version 6.12 (SAS Institute, Cary, N.C.) to perform our statistical analyses.
We performed analyses for all randomized subjects and for evaluable subjects. We defined evaluable subjects as all randomized subjects with no major protocol violations.
The primary efficacy variables were whole-mouth mean MGI and mean PI scores. The secondary efficacy variables were whole-mouth mean BI scores and interproximal mean MGI, PI and BI scores. We conducted the primary examination at six months postbaseline and the secondary examination at three months postbaseline.
We compared the treatment groups with respect to age and baseline efficacy variables using a one-way analysis of variance model with treatment as a factor. We used a 
2 test to compare the groups with respect to sex and smoking status, and we used a Fisher exact test for race.
A regimen of twice-daily brushing and once-daily interdental cleaning undoubtedly has contributed to better oral health in patients.
For the primary and secondary efficacy variables, we tested the differences between treatments at three and six months by a one-way analysis of covariance model with treatment as a factor and the corresponding baseline value as a covariate. We tested the treatment-by-baseline interactions at the .05 level of significance to assess heterogeneity of slopes. We compared the BFEO group to the BC and BFC groups and the BFC group to the BC group. We tested all comparisons at the .05 level of significance, two-sided.
|
RESULTS
|
|---|
To ensure against any potential bias, we determined the evaluability of all subjects before breaking any blinded codes. We provide the results from only evaluable subjects’ analyses, since the respective randomized subject analyses essentially were identical. We excluded subjects from evaluation for administrative reasons (that is, dropout or poor compliance), concomitant antibiotic use or other significant medical findings.
We enrolled 246 subjects in the study and randomly assigned them to one of the three groups. We considered 241 subjects to be evaluable at either three or six months (81 subjects in the BC group, 81 subjects in the BFC group and 79 subjects in the BFEO group). We considered 237 subjects to be evaluable at both three months and six months postbaseline.
We found no significant differences related to demographic and baseline efficacy variables between treatment groups (sex, P = .102; all other values, P .603). Subjects ranged in age from 18 to 64 years, with a mean age of 37 years. Most were women (67.2 percent), nonsmokers (85.9 percent) and white (71.8 percent).
Primary efficacy variables.
Table 1
and Figure 1 present whole-mouth mean MGI scores, one of the two primary measurements. We noted statistically significant reductions in whole-mouth mean MGI scores in both the BFC and BFEO groups when we compared them with the BC group at three and six months. We found similar results for the BFEO group scores when compared with the BFC group.
TOP
ABSTRACT
MATERIALS AND METHODS
