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

NCT02735395 | Unknown Phase 4

• 1 other identifier: SISNEP/513
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Chronic Periodontitis

Keywords

Periodontal Diseases; Metronidazole; Amoxicillin; Chronic periodontitis; Root Planing

Outcome Measures

Primary Outcomes (1)

• Percentage of subjects reaching ≤ 4 periodontal sites with probing depth (PD) ≥ 5 mm at 12 months

  12 months

Secondary Outcomes (19)

• Number of sites with PD ≥ 5 mm

  Baseline, 3, 6 and 12 months

• Number of sites with PD ≥ 6 mm

  Baseline, 3, 6 and 12 months

• Number of sites with PD ≥ 7 mm

  Baseline, 3, 6 and 12 months

• Reduction in the number of sites with PD ≥ 5 mm

  Baseline, 3, 6 and 12 months

• Reduction in the number of sites with PD ≥ 6 mm

  Baseline, 3, 6 and 12 months

Study Arms (5)

Control

PLACEBO COMPARATOR

Scaling and root planing (SRP) + two placebo pills thrice a day (TID) for 14 days (control group)

Procedure: Scaling and root planing (SRP); Other: Placebo 400 (14 days); Other: Placebo 500

MTZ 250 (7 days)

ACTIVE COMPARATOR

SRP + MTZ (250mg/TID) + AMX, for 7 days and placebos for another 7 days

Procedure: Scaling and root planing (SRP); Drug: Metronidazole 250 (7 days); Drug: Amoxicillin; Other: Placebo 250 (7 days)

MTZ 400 (7 days)

ACTIVE COMPARATOR

SRP + MTZ (400mg/TID) + AMX, for 7 days and placebos for another 7 days

Procedure: Scaling and root planing (SRP); Drug: Metronidazole 400 (7 days); Drug: Amoxicillin; Other: Placebo 400 (7 days)

MTZ 250 (14 days)

ACTIVE COMPARATOR

SRP +MTZ (250mg/TID) + AMX for 14 days

Procedure: Scaling and root planing (SRP); Drug: Metronidazole 250 (14 days); Drug: Amoxicillin

MTZ 400 (14 days)

ACTIVE COMPARATOR

SRP +MTZ (400mg/TID) + AMX for 14 days

Procedure: Scaling and root planing (SRP); Drug: Metronidazole 400 (14 days); Drug: Amoxicillin

Interventions

Scaling and root planing (SRP) PROCEDURE

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.

Control; MTZ 250 (14 days); MTZ 250 (7 days); MTZ 400 (14 days); MTZ 400 (7 days)

Metronidazole 250 (7 days) DRUG

Subjects will intake Metronidazole 250 mg. for 7 days, starting immediately after the first session of Scaling and Root Planing.

MTZ 250 (7 days)

Metronidazole 400 (7 days) DRUG

Subjects will intake Metronidazole 400 mg. for 7 days, starting immediately after the first session of Scaling and Root Planing.

MTZ 400 (7 days)

Metronidazole 250 (14 days) DRUG

Subjects will intake Metronidazole 250 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.

MTZ 250 (14 days)

Metronidazole 400 (14 days) DRUG

Subjects will intake Metronidazole 400 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.

MTZ 400 (14 days)

Amoxicillin DRUG

Subjects will intake Amoxicillin 500 mg. for 14 days, starting immediately after and the first session of Scaling and Root Planing.

MTZ 250 (14 days); MTZ 250 (7 days); MTZ 400 (14 days); MTZ 400 (7 days)

Placebo 250 (7 days) OTHER

Subjects will intake placebo of Metronidazole 250 mg. for 7 days, starting immediately after to intake Metronidazole 250 mg.

MTZ 250 (7 days)

Placebo 400 (7 days) OTHER

Subjects will intake placebo of Metronidazole 400 mg. for 7 days, starting immediately after to intake Metronidazole 400 mg.

MTZ 400 (7 days)

Placebo 400 (14 days) OTHER

Subjects will intake placebo of Metronidazole 400 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.

Control

Placebo 500 OTHER

Subjects will intake placebo of Amoxicillin 500 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.

Control

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Guarulhos: lead

Study Sites (1)

Guarulhos University

Guarulhos, São Paulo, 07023-070, Brazil

Location

Related Publications (18)

• 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.

  PMID: 22220822 BACKGROUND

• Carvalho LH, D'Avila GB, Leao 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. doi: 10.1111/j.1600-051X.2004.00605.x.

  PMID: 15560807 BACKGROUND

• 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.

  PMID: 19254119 BACKGROUND

• 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.

  PMID: 25494600 BACKGROUND

• 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.

  PMID: 23016867 BACKGROUND

• 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. doi: 10.1111/j.1600-051X.2005.00814.x.

  PMID: 16174275 BACKGROUND

• 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.

  PMID: 22882646 BACKGROUND

• 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.

  PMID: 20447259 BACKGROUND

• 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.

  PMID: 24930639 BACKGROUND

• Rabelo CC, Feres M, Goncalves 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.

  PMID: 26087839 BACKGROUND

• 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. doi: 10.1902/jop.2012.110625. Epub 2012 Feb 14.

  PMID: 22220767 BACKGROUND

• 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.

  PMID: 22050545 BACKGROUND

• 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.

  PMID: 21762197 BACKGROUND

• 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.

  PMID: 26928597 BACKGROUND

• 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.

  PMID: 22612369 BACKGROUND

• 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. doi: 10.1111/jcpe.12217.

  PMID: 24834504 BACKGROUND

• Khattri S, Kumbargere Nagraj S, Arora A, Eachempati P, Kusum CK, Bhat KG, Johnson TM, Lodi G. Adjunctive systemic antimicrobials for the non-surgical treatment of periodontitis. Cochrane Database Syst Rev. 2020 Nov 16;11(11):CD012568. doi: 10.1002/14651858.CD012568.pub2.

  PMID: 33197289 DERIVED

• Borges I, Faveri M, Figueiredo LC, Duarte PM, Retamal-Valdes B, Montenegro SCL, Feres M. Different antibiotic protocols in the treatment of severe chronic periodontitis: A 1-year randomized trial. J Clin Periodontol. 2017 Aug;44(8):822-832. doi: 10.1111/jcpe.12721. Epub 2017 Jul 26.

  PMID: 28303587 DERIVED

MeSH Terms

Conditions

Chronic Periodontitis; Periodontal Diseases

Interventions

Tooth Exfoliation; Root Planing; Amoxicillin

Condition Hierarchy (Ancestors)

Periodontitis; Mouth Diseases; Stomatognathic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dental Physiological Phenomena; Digestive System and Oral Physiological Phenomena; Dental Scaling; Dental Prophylaxis; Periodontics; Dentistry; Subgingival Curettage; Preventive Dentistry; Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Magda Feres, Professor

  Guarulhos University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: DDS, MSc, PhD Student

Study Record Dates

• First Submitted: March 22, 2016
• First Posted: April 12, 2016
• Study Start: July 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: December 1, 2020
• Last Updated: January 13, 2020

Record last verified: 2020-01

Locations

BR (1)