Amoxicillin and Metronidazole During Periodontal Treatment

Chronic Periodontitis Clinical Trial

— MOMENT  

Official title:

Influence of Moment of Systemic Metronidazole and Amoxicillin Administration in the Treatment of Chronic Periodontitis: a Randomized Clinical Trial.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02954393
• Other study ID #: CAAE: 32465714.4.1001.5506
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 2015
• Est. completion date: December 2020

Study information

• Verified date: January 2020
• Source: University of Guarulhos
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this multicenter randomized clinical trial is to compare the clinical, microbiological and immunological effects of the adjunctive use of systemic metronidazole plus amoxicillin administered in different phases of the treatment of generalized chronic periodontitis.

Description:

The combination of systemic metronidazole (MTZ) and amoxicillin (AMX) to scaling and root planing (SRP) has shown to be a promising periodontal treatment. However, some essential issues associated with the use of these antibiotics remain to be established. Although these agents are often prescribed after the healing phase of the SRP procedure, there is biological plausibility to support its use in conjunction with the mechanical treatment. However, to date, no placebo controlled randomized clinical trial (RCT) has directly compared these two protocols. Therefore, the aim of this multicentric RCT is to compare the clinical, microbiological and immunological effects of adjunctive systemic MTZ+AMX administered in different phases of the treatment of generalized chronic periodontitis (GChP). 180 subjects with GChP will be randomly assigned into three groups (n=60/group) that will receive SRP-only (control group) or in combination with 400 mg MTZ+500 mg AMX beginning at the first SRP session (group test 1) or after 3 months of its completion (group test 2). All volunteers will receive clinical and microbiological evaluation at baseline, 3, 6 and 12 months, and immunological assessment (levels of 20 chemokines) at baseline and 12 months post-therapy. Nine subgingival biofilm samples will be collected by subject and analyzed for counts and proportions of 40 bacterial species by checkerboard DNA-DNA hybridization. Differences in clinical, microbiological and immunological parameters among groups and over time will be evaluated using the ANOVA, ANCOVA, Chi-square and Tukey tests. Microbiological analyzes will be performed using adjustments for multiple comparisons. Statistical significance will be set at 5%.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 180
• Est. completion date: December 2020
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years and older

Eligibility

Inclusion Criteria:

• =35 years of age;

• at least 15 teeth (excluding third molars and teeth with advanced decay indicated for extraction);

• a minimum of 6 teeth with at least one site each with probing depth (PD) and clinical attachment level (CAL) =5 mm;

• at least 30% of the sites with PD and CAL =4 mm and bleeding on probing (BOP).

Exclusion Criteria:

• pregnancy;

• breastfeeding;

• current smoking and former smoking within the past 5 years;

• systemic diseases that could affect the progression of periodontitis (e.g. diabetes, immunological disorders, osteoporosis);

• scaling and root planing an in the previous 6 months;

• antibiotic therapy in the previous 6 months;

• long-term intake of anti-inflammatory medications;

• need for antibiotic pre-medication for routine dental therapy;

• use of orthodontic appliances;

• extensive dental prosthetic rehabilitation;

• allergy to metronidazole and/or amoxicillin.

Related Conditions & MeSH terms

• Chronic Periodontitis
• Periodontitis

Intervention

Procedure:
• Scaling and root planing
SRP will be performed in four to six appointments lasting approximately 1 h each, using manual curettes (Hu-Friedy, Chicago, IL, USA) and ultrasonic device (Cavitron Select SPC, Dentsply professional, York, PA, USA) under local anesthesia. The deep sites will be scaled throughout the first week and treatment of the entire oral cavity will be completed in 14 days.

Drug:
• Metronidazole active phase
Metronidazole 400 mg thrice a day for 14 days in the active phase of the periodontal treatment (beginning with the first SRP session).
• Metronidazole healing phase
Metronidazole 400 mg thrice a day for 14 days in the healing phase of the periodontal treatment (3 months after active phase).
• Amoxicillin active phase
Amoxicillin 500 mg thrice a day for 14 days in the active phase of the periodontal treatment (beginning with the first SRP session).
• Amoxicillin healing phase
Amoxicillin 500 mg thrice a day for 14 days in the healing phase of the periodontal treatment (3 months after active phase).
• Placebos active phase
Amoxicillin and metronidazole placebos thrice a day for 14 days in the active phase (beginning with the first SRP session).
• Placebos healing phase
Amoxicillin and metronidazole placebos thrice a day for 14 days in the healing phase (3 months after active phase).

Locations

Country	Name	City	State
Brazil	University of Guarulhos	Guarulhos	São Paulo
Brazil	University of São Paulo	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Belén Retamal-Valdes

Country where clinical trial is conducted

Brazil, 

References & Publications (18)

Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol. 1999 Dec;4(1):1-6. Review. — View Citation

Feres M, Figueiredo LC, Soares GM, Faveri M. Systemic antibiotics in the treatment of periodontitis. Periodontol 2000. 2015 Feb;67(1):131-86. doi: 10.1111/prd.12075. Review. — View Citation

Feres M, Soares GM, Mendes JA, Silva MP, Faveri M, Teles R, Socransky SS, Figueiredo LC. Metronidazole alone or with amoxicillin as adjuncts to non-surgical treatment of chronic periodontitis: a 1-year double-blinded, placebo-controlled, randomized clinical trial. J Clin Periodontol. 2012 Dec;39(12):1149-58. doi: 10.1111/jcpe.12004. Epub 2012 Sep 27. — View Citation

Haffajee AD, Patel M, Socransky SS. Microbiological changes associated with four different periodontal therapies for the treatment of chronic periodontitis. Oral Microbiol Immunol. 2008 Apr;23(2):148-57. doi: 10.1111/j.1399-302X.2007.00403.x. — View Citation

Herrera D, Sanz M, Jepsen S, Needleman I, Roldán S. A systematic review on the effect of systemic antimicrobials as an adjunct to scaling and root planing in periodontitis patients. J Clin Periodontol. 2002;29 Suppl 3:136-59; discussion 160-2. Review. — View Citation

Keestra JA, Grosjean I, Coucke W, Quirynen M, Teughels W. Non-surgical periodontal therapy with systemic antibiotics in patients with untreated chronic periodontitis: a systematic review and meta-analysis. J Periodontal Res. 2015 Jun;50(3):294-314. doi: 10.1111/jre.12221. Epub 2014 Aug 21. Review. — View Citation

Lang NP, Tonetti MS. Periodontal risk assessment (PRA) for patients in supportive periodontal therapy (SPT). Oral Health Prev Dent. 2003;1(1):7-16. — View Citation

Matuliene G, Pjetursson BE, Salvi GE, Schmidlin K, Brägger U, Zwahlen M, Lang NP. Influence of residual pockets on progression of periodontitis and tooth loss: results after 11 years of maintenance. J Clin Periodontol. 2008 Aug;35(8):685-95. doi: 10.1111/j.1600-051X.2008.01245.x. Epub 2008 Jul 23. — View Citation

Matuliene G, Studer R, Lang NP, Schmidlin K, Pjetursson BE, Salvi GE, Brägger U, Zwahlen M. Significance of Periodontal Risk Assessment in the recurrence of periodontitis and tooth loss. J Clin Periodontol. 2010 Feb;37(2):191-9. doi: 10.1111/j.1600-051X.2009.01508.x. Epub 2009 Dec 21. — View Citation

Mestnik MJ, Feres M, Figueiredo LC, Duarte PM, Lira EA, Faveri M. Short-term benefits of the adjunctive use of metronidazole plus amoxicillin in the microbial profile and in the clinical parameters of subjects with generalized aggressive periodontitis. J Clin Periodontol. 2010 Apr;37(4):353-65. doi: 10.1111/j.1600-051X.2010.01538.x. — View Citation

Mestnik MJ, Feres M, Figueiredo LC, Soares G, Teles RP, Fermiano D, Duarte PM, Faveri M. The effects of adjunctive metronidazole plus amoxicillin in the treatment of generalized aggressive periodontitis: a 1-year double-blinded, placebo-controlled, randomized clinical trial. J Clin Periodontol. 2012 Oct;39(10):955-61. doi: 10.1111/j.1600-051X.2012.01932.x. Epub 2012 Aug 6. — View Citation

Sgolastra F, Gatto R, Petrucci A, Monaco A. Effectiveness of systemic amoxicillin/metronidazole as adjunctive therapy to scaling and root planing in the treatment of chronic periodontitis: a systematic review and meta-analysis. J Periodontol. 2012 Oct;83(10):1257-69. Epub 2012 Feb 14. Review. — View Citation

Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL Jr. Microbial complexes in subgingival plaque. J Clin Periodontol. 1998 Feb;25(2):134-44. — View Citation

Socransky SS, Haffajee AD, Smith C, Dibart S. Relation of counts of microbial species to clinical status at the sampled site. J Clin Periodontol. 1991 Nov;18(10):766-75. — View Citation

Socransky SS, Haffajee AD. Dental biofilms: difficult therapeutic targets. Periodontol 2000. 2002;28:12-55. Review. — View Citation

Socransky SS, Haffajee AD. Periodontal microbial ecology. Periodontol 2000. 2005;38:135-87. Review. — View Citation

Socransky SS, Smith C, Martin L, Paster BJ, Dewhirst FE, Levin AE. "Checkerboard" DNA-DNA hybridization. Biotechniques. 1994 Oct;17(4):788-92. — View Citation

Teles RP, Haffajee AD, Socransky SS. Microbiological goals of periodontal therapy. Periodontol 2000. 2006;42:180-218. Review. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of subjects reaching = 4 periodontal sites with probing depth (PD) = 5 mm at 12 months		12 months
Secondary	Number of sites with PD = 5 mm.		Baseline, 3, 6 and 12 months.
Secondary	Number of sites with PD = 6 mm.		Baseline, 3, 6 and 12 months.
Secondary	Number of sites with PD = 7 mm.		Baseline, 3, 6 and 12 months.
Secondary	Reduction in the number of sites with PD = 5 mm.		Baseline, 3, 6 and 12 months.
Secondary	Reduction in the number of sites with PD = 6 mm.		Baseline, 3, 6 and 12 months.
Secondary	Reduction in the number of sites with PD = 7 mm.		Baseline, 3, 6 and 12 months.
Secondary	Mean PD changes in sites with initial PD between 4-6 mm		Baseline - 12 months.
Secondary	Mean PD changes in sites with initial PD = 7 mm.		Baseline - 12 months.
Secondary	Mean CAL changes in sites with initial CAL between 4-6 mm		Baseline - 12 months.
Secondary	Mean CAL changes in sites with initial CAL = 7 mm.		Baseline - 12 months.
Secondary	Full-mouth PD.		Baseline, 3, 6 and 12 months.
Secondary	Full-mouth clinical attachment level.		Baseline, 3, 6 and 12 months.
Secondary	Percentage of sites with bleeding on probing.		Baseline, 3, 6 and 12 months.
Secondary	Percentage of sites with plaque accumulation		Baseline, 3, 6 and 12 months.
Secondary	Percentage of sites with marginal bleeding.		Baseline, 3, 6 and 12 months.
Secondary	Occurrence of headache obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Occurrence of vomiting obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Occurrence of diarrhea obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Occurrence of metallic taste obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Occurrence of nausea obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Occurrence of irritability obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Proportions of periodontal pathogenic bacterial species.		Baseline, 3, 6 and 12 months.
Secondary	Counts of periodontal pathogenic bacterial species.		Baseline, 3, 6 and 12 months.
Secondary	Counts of chemokines in the crevicular gingival fluid.		Baseline and 12 months.