Comparing the Effect of 0.06%, 0.12% and 0.2% Chlorhexidine on Plaque, Bleeding and Side Effects in an Experimental Gingivitis Model

A Parallel Group, Double Masked Randomized Clinical Trial

Maliha Haydari; Ayse Gul Bardakci; Odd Carsten Koldsland; Anne Merete Aass; Leiv Sandvik; Hans R. Preus

Disclosures

BMC Oral Health. 2017;17(118) 

In This Article

Methods

The present study was designed as a parallel group, double masked, randomized clinical trial. The experimental gingivitis model,[13] with the modifications by Preus et al.[14,15] was used to induce gingival inflammation under supervised conditions throughout the study. The Regional Committee for Medical Research Ethics, South East Norway, approved the study (REK 2016/1748). The U.S. National Institute of Health Clinical Trials Registry number is NCT02911766 (http://www.clinicaltrials.gov). The study adheres to the CONSORT guidelines.

The study population comprised 60 dental, medical, and dental hygienist students who volunteered to participate in the project. A meeting was arranged for the volunteers prior to the start of the study, through which the participants received information about oral rinsing products in general and CHX containing products as well as information on the study ahead, in particular. At this meeting 68 students showed their interest, but 6 withdrew because they realized that they had to abstain from tooth cleaning in quadrant 1 for 21 days. Two students were not eligible due to regular use of smokeless tobacco (Figure 1).

Figure 1.

Patient flow diagram

Mean age of the participants was 21 years and 72% were females. The study period was 21 days in November 2016. All information, administration and data collection was performed at the Department of Periodontology, Institute of Clinical Odontology, Faculty of Dentistry, University of Oslo, Norway.

Inclusion criteria comprised healthy subjects of both genders, aged 18 years and older, having at least three of the following teeth in maxillary right and left quadrant: the canine, 1st bicuspid, 2nd bicuspid, 1st molar, healthy gingiva and periodontium. Exclusion criteria comprised smoking and/or use of non-smoking tobacco, pregnancy, lactation, any chronic diseases, clinical signs or symptoms of acute infection in the oral cavity, any prescribed or non-prescription systemic or topical medication except oral contraceptives, use of systemic antibiotics the last 3 months prior to the start of the study, history of alcohol or drug abuse or participation in other clinical studies in the last 4 weeks. Before inclusion, every participant signed an informed consent form in which anonymity was granted and confirmed.

The test solutions were the commercially available mouthwashes: 0.2% CHX,1 0.12% CHX with 910 ppm NaF2 and 0.06% CHX with 250 ppm NaF.3 The three commercially available CHX mouthwashes were filled in identical, but differently labeled (A,B,C) bottles for blinding purposes. The 0.2% and the 0.06% CHX products were bought at a local pharmacy, whereas the 0.12% was donated to the project by the manufacturer.

Simple, restricted randomization was carried out using a computer generated random allocation Table[16] assigning the participants to the three study groups with 20 test subjects in each. They were all carefully instructed to rinse for 60 s. twice a day as recommended by the manufacturers.

Setting the baseline dental plaque score to zero was done by giving all participants a professional tooth cleaning with rubber cup, pumice paste and dental floss at the start of the study. The participants were given their test solution and subsequently instructed to rinse as described above. All information was given verbally as well as in writing.

Individual plastic tooth guards had been produced to fit the teeth in the upper right quadrant (Q1).[14,15] Together with this individual tooth guard, the participants were given identical prophylaxis packs containing a medium texture tooth brush, inter-dental floss and dentifrice and were instructed to insert the tooth guard in Q1 every time they brushed their teeth and to perform a mechanical oral hygiene routine twice daily in the three other quadrants. They should then rinse 30 s with tap water before and after removing the tooth guard. Following this procedure, the participants rinsed, as instructed, with the solution they randomly had been assigned, repeating the procedure for 21 days. Following the scoring at day 21, the participants received professional tooth cleaning after ending the study.

A team of five people were trained in the procedure of informing participants, receiving the test persons for evaluation, questionnaire and clinically monitoring them.[15] The principal investigator (HRP) and project managers (MH/AGB) managed all contact with the participants outside the scoring room. In between appointments the project team kept in touch with the test persons by text messaging and e-mail. The success of this service was evident by zero no-shows at the clinic.

At the interviews at day 7, 14 and 21 the project managers (MH/AGB) received reports from each participant about adherence to protocol as well as verbal complaints and descriptions of subjective side-effects. A special, assisted questionnaire had been prepared for these interviews. Reports of ill- and side effects were registered and categorized for later statistical evaluation. To investigate a possible recognition effect among the participants they were also asked if they had recognized the taste and knew (no guessing) which rinsing compound they were assigned to (Additional File 1, assisted questionnaire).

At day 21, the above mentioned interview was followed by an examination of clinical results. Before entering the scoring room MH/AGB advised the participants to refrain from any conversation with the scoring scientists inside, who had been instructed likewise. In the scoring room, two researchers (AMA, OCK) obtained the clinical data. Plaque index (PI) and gingival index (GI)[12] were recorded on the mesial, buccal, distal and palatal aspects of teeth 16, 15, 14, 13 and 23, 24, 25, 26. Adverse events like discoloration observed during the clinical examination (yes/no) and clinically visible oral mucosal reactions were registered. In addition the plaque index by Quigley and Hine, the Turesky modification[11] was finally registered. All clinical registrations were performed by the same experienced periodontist (AMA), leaving her colleague (OCK) to register recordings on specially designed charts. The clinical crew was kept blind to the group allocation of the participants at all times, as the statistician was the only one that had access to the code-book, and he did not participate in any clinical event.

Statistics

The present experiment aimed at comparing the plaque and gingivitis preventing effect of the 0.12% CHX and 0.06% CHX solutions with the gold standard 0.2% CHX solution4 (no alcohol).

The total number of participants was 60, with 20 participants in each group. The number of participants was based on the following power calculation. The power analysis was based on the variable 'average plaque score in each participant' (APS). When comparing APS in two groups, a two-sided independent samples t-test was used, with 5% significance level. Average standard deviation in the 3 groups was 0.40. It may be shown that in order to have 80% test power to detect a mean difference in APS of at least 0.40 between two groups, at least 15 participants must be included in each group. Because some drop-outs were expected, it was decided to include 60 subjects in the study. Because 80% test power is generally accepted as sufficiently high in clinical studies, and the mean difference in mesial plaque score between group 1 and group 3 was 0.41, the above calculation suggest that our study had acceptable test power.

When comparing mean plaque score in two groups, a two-sided independent sample t-test was used, with a 5% significance level. When comparing proportion of subjects with a particular adverse effect, the "linear by linear association chi-square" test was used. The statistical analysis was conducted using the software of SPSS for Windows, Version 16.0 (SPSS Inc., Chicago, IL).

The distributions of the outcome variables were checked, and found to be sufficiently close to the normal distribution to allow for the use of a t-test.

1Corsodyl (0.2%), GSK, Norway
2Flux Pro Klorhexidine (0.12%), Actavis, Norway
3Corsodaily® (0.06%), GSK, Norway
4Corsodyl 0.2% CHX has been alcohol free since 2012

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