Dose and Duration of Metronidazole and Amoxicillin for Treatment of Chronic Periodontitis

Chronic Periodontitis Clinical Trial

Official title:

Impact of Different Dosages and Time of Administration of Metronidazole and Amoxicillin in the Treatment of Generalized Chronic Periodontitis: A Randomized Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02735395
• Other study ID #: SISNEP/513
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: July 2011
• 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 study was to compare the clinical and microbiological outcomes of different dosages of metronidazole (MTZ) and of the duration of the systemic administration of MTZ and amoxicillin as adjunct to scaling and root planing (SRP) in the treatment of generalized chronic periodontitis (GChP).

Description:

Randomized clinical trials and systematic reviews have shown that the use of the combination of metronidazole (MTZ) and amoxicillin (AMX) significantly improves the benefits of the SRP in the treatment of subjects with periodontitis. However, the optimal dosage and interval of administration of these antibiotics are still unclear. Therefore, the aim of this study was to compare the clinical and microbiological outcomes of different dosages and duration of the systemic administration of the combination of MTZ and AMX as adjunct to scaling and root planing (SRP) in the treatment of generalized chronic periodontitis (GChP). One hundred ten subjects will be randomly assigned to receive SRP plus placebo, or SRP combined with 250 mg or 400 mg of MTZ, plus AMX (500 mg) TID, for either 7 or 14 days. Subjects will be clinically and microbiologically monitored up to 1 year post-therapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 110
• Est. completion date: December 2020
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

Inclusion Criteria:

• =30 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 12 months;

• antibiotic therapy in the previous 6 months;

• long-term intake of anti-inflammatory medications;

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

• allergy to metronidazole and/or amoxicillin.

Related Conditions & MeSH terms

• Chronic Periodontitis
• Periodontitis

Intervention

Procedure:
• Scaling and root planing (SRP)
SRP 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 250 (7 days)
Subjects will intake Metronidazole 250 mg. for 7 days, starting immediately after the first session of Scaling and Root Planing.
• Metronidazole 400 (7 days)
Subjects will intake Metronidazole 400 mg. for 7 days, starting immediately after the first session of Scaling and Root Planing.
• Metronidazole 250 (14 days)
Subjects will intake Metronidazole 250 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.
• Metronidazole 400 (14 days)
Subjects will intake Metronidazole 400 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.
• Amoxicillin
Subjects will intake Amoxicillin 500 mg. for 14 days, starting immediately after and the first session of Scaling and Root Planing.

Other:
• Placebo 250 (7 days)
Subjects will intake placebo of Metronidazole 250 mg. for 7 days, starting immediately after to intake Metronidazole 250 mg.
• Placebo 400 (7 days)
Subjects will intake placebo of Metronidazole 400 mg. for 7 days, starting immediately after to intake Metronidazole 400 mg.
• Placebo 400 (14 days)
Subjects will intake placebo of Metronidazole 400 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.
• Placebo 500
Subjects will intake placebo of Amoxicillin 500 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.

Locations

Country	Name	City	State
Brazil	Guarulhos University	Guarulhos	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
University of Guarulhos

Country where clinical trial is conducted

Brazil, 

References & Publications (16)

Aimetti M, Romano F, Guzzi N, Carnevale G. Full-mouth disinfection and systemic antimicrobial therapy in generalized aggressive periodontitis: a randomized, placebo-controlled trial. J Clin Periodontol. 2012 Mar;39(3):284-94. doi: 10.1111/j.1600-051X.2011.01795.x. Epub 2012 Jan 4. — View Citation

Carvalho LH, D'Avila GB, Leão A, Haffajee AD, Socransky SS, Feres M. Scaling and root planing, systemic metronidazole and professional plaque removal in the treatment of chronic periodontitis in a Brazilian population. I. clinical results. J Clin Periodontol. 2004 Dec;31(12):1070-6. — View Citation

Cionca N, Giannopoulou C, Ugolotti G, Mombelli A. Amoxicillin and metronidazole as an adjunct to full-mouth scaling and root planing of chronic periodontitis. J Periodontol. 2009 Mar;80(3):364-71. doi: 10.1902/jop.2009.080540 . — 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

Guerrero A, Griffiths GS, Nibali L, Suvan J, Moles DR, Laurell L, Tonetti MS. Adjunctive benefits of systemic amoxicillin and metronidazole in non-surgical treatment of generalized aggressive periodontitis: a randomized placebo-controlled clinical trial. J Clin Periodontol. 2005 Oct;32(10):1096-107. — 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

Miranda TS, Feres M, Perez-Chaparro PJ, Faveri M, Figueiredo LC, Tamashiro NS, Bastos MF, Duarte PM. Metronidazole and amoxicillin as adjuncts to scaling and root planing for the treatment of type 2 diabetic subjects with periodontitis: 1-year outcomes of a randomized placebo-controlled clinical trial. J Clin Periodontol. 2014 Sep;41(9):890-9. doi: 10.1111/jcpe.12282. Epub 2014 Jul 17. — View Citation

Rabelo CC, Feres M, Gonçalves C, Figueiredo LC, Faveri M, Tu YK, Chambrone L. Systemic antibiotics in the treatment of aggressive periodontitis. A systematic review and a Bayesian Network meta-analysis. J Clin Periodontol. 2015 Jul;42(7):647-57. doi: 10.1111/jcpe.12427. Review. — 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

Sgolastra F, Petrucci A, Gatto R, Monaco A. Effectiveness of systemic amoxicillin/metronidazole as an adjunctive therapy to full-mouth scaling and root planing in the treatment of aggressive periodontitis: a systematic review and meta-analysis. J Periodontol. 2012 Jun;83(6):731-43. doi: 10.1902/jop.2011.110432. Epub 2011 Nov 3. Review. — View Citation

Silva MP, Feres M, Sirotto TA, Soares GM, Mendes JA, Faveri M, Figueiredo LC. Clinical and microbiological benefits of metronidazole alone or with amoxicillin as adjuncts in the treatment of chronic periodontitis: a randomized placebo-controlled clinical trial. J Clin Periodontol. 2011 Sep;38(9):828-37. doi: 10.1111/j.1600-051X.2011.01763.x. Epub 2011 Jul 15. — View Citation

Soares GM, Mendes JA, Silva MP, Faveri M, Teles R, Socransky SS, Wang X, Figueiredo LC, Feres M. Metronidazole alone or with amoxicillin as adjuncts to non-surgical treatment of chronic periodontitis: a secondary analysis of microbiological results from a randomized clinical trial. J Clin Periodontol. 2014 Apr;41(4):366-76. — View Citation

Zandbergen D, Slot DE, Cobb CM, Van der Weijden FA. The clinical effect of scaling and root planing and the concomitant administration of systemic amoxicillin and metronidazole: a systematic review. J Periodontol. 2013 Mar;84(3):332-51. doi: 10.1902/jop.2012.120040. Epub 2012 May 21. Review. — View Citation

Zandbergen D, Slot DE, Niederman R, Van der Weijden FA. The concomitant administration of systemic amoxicillin and metronidazole compared to scaling and root planing alone in treating periodontitis: =a systematic review=. BMC Oral Health. 2016 Feb 29;16:27. doi: 10.1186/s12903-015-0123-6. Review. — View Citation

* Note: There are 16 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	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 the beginning of treatments
Secondary	Occurrence of vomiting obtained through a questionnaire of adverse effects		14 days after the beginning of treatments
Secondary	Occurrence of diarrhea obtained through a questionnaire of adverse effects		14 days after the beginning of treatments
Secondary	Occurrence of metallic taste obtained through a questionnaire of adverse effects		14 days after the beginning of treatments
Secondary	Occurrence of nausea obtained through a questionnaire of adverse effects		14 days after the beginning of treatments
Secondary	Occurrence of irritability obtained through a questionnaire of adverse effects		14 days after the beginning of treatments
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