Efficacy of Different Chlorhexidine Concentrations

Gingivitis Clinical Trial

Official title:

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, Double Masked, Randomized, Placebo-controlled Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02911766
• Other study ID #: 2015/608453
• Status: Not yet recruiting
• Phase: Phase 4
• First received: September 9, 2016
• Last updated: October 4, 2016
• Start date: November 2016
• Est. completion date: December 2016

Study information

• Verified date: October 2016
• Source: University of Oslo
• Contact: Hans R Preus, PhD
• Phone: +47 22852163
• Email: hpreus[@]odont.uio.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Chlorhexidine is the gold standard of dental plaque prevention, but which concentration is the most effective is not known. The aim of the present study was to compare the plaque and gingivitis inhibiting effect of commercial products containing 0.2%, 0.12% and 0.06% chlorhexidine in a modified experimental gingivitis model.

In three groups of healthy volunteers, experimental gingivitis was induced and monitored over 21days, simultaneously treated with the commercial solutions containing 0.2%, 0.12% and 0.06% chlorhexidine. The maxillary right quadrant of each individual received mouthwash only, whereas the maxillary left quadrant was subject to both rinsing and mechanical oral hygiene. Compliance and side effects were monitored at days 7, 14, and 21. Plaque and gingivitis scores were obtained at baseline and day 21.

The commercial mouthwash containing 0.2% chlorhexidine resulted in statistically significantly lower plaque scores than the 0.12 and 0.06% mouthwashes after 21 days use, whereas no statistically significant difference was found between the effect of the two latter mouthrinses.

A commercial available mouthwash containing 0.2% chlorhexidine proved statistically significant better effect in preventing dental plaque than 0.12% and 0.06% solutions.

Description:

The present study was designed as a parallel, double masked, randomized, placebo-controlled clinical trial. The experimental gingivitis model, with the modifications by Preus and coworkers was used to induce gingival inflammation under supervised conditions throughout the study.

The study population comprised sixty 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 chlorhexidine containing products as well as information on the study ahead, in particular.

The study period was 21 days, not comprising any special academic, religious or ethnic events that could jeopardize the collective behavior of the study population. All information, administration and data collection was performed at the Department of Periodontology, Institute of Clinical Odontology, Faculty of Dentistry, University of Oslo, Norway.

The test solutions were the commercially available mouthwash products: 0.2 % chlorhexidine (no ethanol), 0.12% chlorhexidine with 910 ppm Sodium Fluoride (NaF) without ethanol and 0.06% chlorhexidine 250ppm Sodium Fluoride (NaF). The three commercially available chlorhexidine solutions were filled in identical, but differently labelled (A,B,C) plastic bottles for blinding purposes.

Randomization was carried out using a computer generated random allocation table, assigning the participants to the three study groups with 20 test subjects in each. They were all carefully instructed to rinse for 60 sec. 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. Together with this individual tooth guard, the students were given identical prophylaxis packs containing a medium texture tooth brush, inter-dental floss and dentifrice. The participants were instructed to substitute their daily oral hygiene remedies with the ones given to them, and attach the tooth guard to the tooth brush, with a provided rubber string, before and after use so that the use of this always was remembered when using the brush.

The participants were instructed to insert the tooth guard in the first quadrant 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 sec with tap water before and after removing the tooth guard to remove as much as possible of the remnants of the dentifrice. 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. The principal investigator and project managers 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, as was the case also in the previous studies with this design.

At the interviews at day 7, 14, 21 the project managers received reports from each participant about compliance (adherence to protocol) and verbal complaints and descriptions of subjective side-effects. A special questionnaire had been prepared for these interviews. Reports of ill- and side effects were carefully registered and categorized for later statistical examination.

At day 21, the above mentioned interview was followed by an examination of clinical results. Before entering the scoring room the project managers advised the participants to refrain from any conversation with the scoring scientists inside. The recorders had been instructed likewise. In the scoring room, two researchers obtained the clinical data. The Loe and Silness plaque - and gingival index 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, plaque index by Quigley and Hine, the Turesky modification, was registered. All clinical registrations were performed by the same experienced periodontist, leaving her colleague 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 only one that had access to the code-book was the statistician who did not participate in the clinical events.

Statistics The present experiment aimed at comparing the plaque and gingivitis preventing effect of the 0.12% - and 0.06% chlorhexidine solutions with the gold standard 0.2% chlorhexidine group.

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'. When comparing average plaque scores 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 average plaque score 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 the 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 Statistical Package for the Social Sciences (SPSS) for Windows, Version 16.0.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 59
• Est. completion date: December 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 42 Years

Eligibility

Inclusion Criteria:

• non-smoking subjects,

• healthy subjects

• 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:

• 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

• participation in other clinical studies in the last 4 weeks.

Related Conditions & MeSH terms

• Dental Plaque
• Gingivitis

Intervention

Drug:
• Chlorhexidine 0.2% Mouthrinse
Intervention; Rinsing 60 sec with Comparator solution twice daily for 21 days
• Chlorhexidine 0.12% mouthrinse
Intervention; Rinsing 60 sec with Comparator solution twice daily for 21 days
• Chlorhexidine 0.06% mouthrinse
Intervention; Rinsing 60 sec with Comparator solution twice daily for 21 days

Locations

Country	Name	City	State
Norway	Department of Periodontology, Institute of Clinical Odontology, Dental Faculty, University of Oslo	Oslo

Sponsors (1)

Lead Sponsor	Collaborator
University of Oslo

Country where clinical trial is conducted

Norway, 

References & Publications (25)

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Altman DG. Clinical trials. Practical statistics for medical research. London: Chapman & Hall/CRC; 1991. p 456.

Berchier CE, Slot DE, Van der Weijden GA. The efficacy of 0.12% chlorhexidine mouthrinse compared with 0.2% on plaque accumulation and periodontal parameters: a systematic review. J Clin Periodontol. 2010 Sep;37(9):829-39. doi: 10.1111/j.1600-051X.2010.01 — View Citation

Davies A. The mode of action of chlorhexidine. J Periodontal Res Suppl. 1973;12:68-75. — View Citation

Denton, G. W. Disinfection, Sterilization and Preservation, 4th ed, pp. 274-89.

Franco Neto CA, Parolo CC, Rösing CK, Maltz M. Comparative analysis of the effect of two chlorhexidine mouthrinses on plaque accumulation and gingival bleeding. Braz Oral Res. 2008 Apr-Jun;22(2):139-44. — View Citation

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Keijser JA, Verkade H, Timmerman MF, Van der Weijden FA. Comparison of 2 commercially available chlorhexidine mouthrinses. J Periodontol. 2003 Feb;74(2):214-8. — View Citation

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Löe H. The Gingival Index, the Plaque Index and the Retention Index Systems. J Periodontol. 1967 Nov-Dec;38(6):Suppl:610-6. — View Citation

Owens J, Addy M, Faulkner J, Lockwood C, Adair R. A short-term clinical study design to investigate the chemical plaque inhibitory properties of mouthrinses when used as adjuncts to toothpastes: applied to chlorhexidine. J Clin Periodontol. 1997 Oct;24(10 — View Citation

Pizzo G, Guiglia R, Imburgia M, Pizzo I, D'Angelo M, Giuliana G. The effects of antimicrobial sprays and mouthrinses on supragingival plaque regrowth: a comparative study. J Periodontol. 2006 Feb;77(2):248-56. — View Citation

Preus HR, Aass AM, Hansen BF, Moe B, Gjermo P. A randomized, single-blind, parallel-group clinical study to evaluate the effect of soluble beta-1,3/1,6-glucan on experimental gingivitis in man. J Clin Periodontol. 2008 Mar;35(3):236-41. doi: 10.1111/j.160 — View Citation

Preus HR, Dahlen G, Gjermo P, Baelum V. Microbiologic Observations After Four Treatment Strategies Among Patients With Periodontitis Maintaining a High Standard of Oral Hygiene: Secondary Analysis of a Randomized Controlled Clinical Trial. J Periodontol. — View Citation

Preus HR, Koldsland OC, Aass AM, Sandvik L, Hansen BF. The plaque- and gingivitis-inhibiting capacity of a commercially available essential oil product. A parallel, split-mouth, single blind, randomized, placebo-controlled clinical study. Acta Odontol Sca — View Citation

QUIGLEY GA, HEIN JW. Comparative cleansing efficiency of manual and power brushing. J Am Dent Assoc. 1962 Jul;65:26-9. — View Citation

Quirynen M, Avontroodt P, Peeters W, Pauwels M, Coucke W, van Steenberghe D. Effect of different chlorhexidine formulations in mouthrinses on de novo plaque formation. J Clin Periodontol. 2001 Dec;28(12):1127-36. — View Citation

Smith RG, Moran J, Addy M, Doherty F, Newcombe RG. Comparative staining in vitro and plaque inhibitory properties in vivo of 0.12% and 0.2% chlorhexidine mouthrinses. J Clin Periodontol. 1995 Aug;22(8):613-7. — View Citation

Turesky S, Gilmore ND, Glickman I. Reduced plaque formation by the chloromethyl analogue of victamine C. J Periodontol. 1970 Jan;41(1):41-3. — View Citation

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Vatne JF, Gjermo P, Sandvik L, Preus HR. Patients' perception of own efforts versus clinically observed outcomes of non-surgical periodontal therapy in a Norwegian population: an observational study. BMC Oral Health. 2015 May 17;15:61. doi: 10.1186/s12903 — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Side effects	All reported side subjective side effects like "taste perturbation" (Yes/No) "numbness" (Yes/No) "soar tongue tip" (Yes/No) "Mucosal ulcers" (yes/No)	21 days
Other	subjective and objective discoloration of teeth	Discoloration of dental surfaces (Yes/No)	21 days
Primary	Plaque index of Silness and Loe (PI) 1964	0= No plaque; A film of plaque adhering to the free gingival margin and adjacent area of the tooth. The plaque may be seen in situ only after application of disclosing solution or by using the probe on the tooth surface.; Moderate accumulation of soft deposit s within the gingival pocket, or the tooth and gingival margin which can be seen with the naked eye.; Abundance of soft matter within the gingival pocket and/or on the tooth and gingival margin.	21 days
Secondary	Gingival index of Løe (GI) and Silness 1963	0 No inflammation.; Mild inflammation, slight change in color, slight edema, no bleeding on probing.; Moderate inflammation, moderate glazing, redness, bleeding on probing.; Severe inflammation, marked redness and hypertrophy, ulceration, tendency to spontaneous bleeding.	21 days