Back to resultsDose and Duration of Metronidazole and Amoxicillin for Treatment of Chronic Periodontitis
Primary Purpose
Chronic Periodontitis
Status
Unknown status
Phase
Phase 4
Locations
Brazil
Study Type
Interventional
Intervention
Scaling and root planing (SRP)
Metronidazole 250 (7 days)
Metronidazole 400 (7 days)
Metronidazole 250 (14 days)
Metronidazole 400 (14 days)
Amoxicillin
Placebo 250 (7 days)
Placebo 400 (7 days)
Placebo 400 (14 days)
Placebo 500
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Periodontitis focused on measuring Periodontal Diseases, Metronidazole, Amoxicillin, Chronic periodontitis, Root Planing
Eligibility Criteria
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.
Sites / Locations
- Guarulhos University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Placebo Comparator
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
Control
MTZ 250 (7 days)
MTZ 400 (7 days)
MTZ 250 (14 days)
MTZ 400 (14 days)
Arm Description
Scaling and root planing (SRP) + two placebo pills thrice a day (TID) for 14 days (control group)
SRP + MTZ (250mg/TID) + AMX, for 7 days and placebos for another 7 days
SRP + MTZ (400mg/TID) + AMX, for 7 days and placebos for another 7 days
SRP +MTZ (250mg/TID) + AMX for 14 days
SRP +MTZ (400mg/TID) + AMX for 14 days
Outcomes
Primary Outcome Measures
Percentage of subjects reaching ≤ 4 periodontal sites with probing depth (PD) ≥ 5 mm at 12 months
Secondary Outcome Measures
Number of sites with PD ≥ 5 mm
Number of sites with PD ≥ 6 mm
Number of sites with PD ≥ 7 mm
Reduction in the number of sites with PD ≥ 5 mm
Reduction in the number of sites with PD ≥ 6 mm
Reduction in the number of sites with PD ≥ 7 mm
Full-mouth PD
Full-mouth clinical attachment level
Percentage of sites with bleeding on probing
Percentage of sites with plaque accumulation
Percentage of sites with marginal bleeding
Occurrence of headache obtained through a questionnaire of adverse effects
Occurrence of vomiting obtained through a questionnaire of adverse effects
Occurrence of diarrhea obtained through a questionnaire of adverse effects
Occurrence of metallic taste obtained through a questionnaire of adverse effects
Occurrence of nausea obtained through a questionnaire of adverse effects
Occurrence of irritability obtained through a questionnaire of adverse effects
Proportions of periodontal pathogenic bacterial species
Counts of periodontal pathogenic bacterial species
Full Information
NCT ID
NCT02735395
First Posted
March 22, 2016
Last Updated
January 8, 2020
Sponsor
University of Guarulhos
1. Study Identification
Unique Protocol Identification Number
NCT02735395
Brief Title
Dose and Duration of Metronidazole and Amoxicillin for Treatment of Chronic Periodontitis
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
July 2011 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
December 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Guarulhos
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Periodontitis
Keywords
Periodontal Diseases, Metronidazole, Amoxicillin, Chronic periodontitis, Root Planing
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
110 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Scaling and root planing (SRP) + two placebo pills thrice a day (TID) for 14 days (control group)
Arm Title
MTZ 250 (7 days)
Arm Type
Active Comparator
Arm Description
SRP + MTZ (250mg/TID) + AMX, for 7 days and placebos for another 7 days
Arm Title
MTZ 400 (7 days)
Arm Type
Active Comparator
Arm Description
SRP + MTZ (400mg/TID) + AMX, for 7 days and placebos for another 7 days
Arm Title
MTZ 250 (14 days)
Arm Type
Active Comparator
Arm Description
SRP +MTZ (250mg/TID) + AMX for 14 days
Arm Title
MTZ 400 (14 days)
Arm Type
Active Comparator
Arm Description
SRP +MTZ (400mg/TID) + AMX for 14 days
Intervention Type
Procedure
Intervention Name(s)
Scaling and root planing (SRP)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Metronidazole 250 (7 days)
Intervention Description
Subjects will intake Metronidazole 250 mg. for 7 days, starting immediately after the first session of Scaling and Root Planing.
Intervention Type
Drug
Intervention Name(s)
Metronidazole 400 (7 days)
Intervention Description
Subjects will intake Metronidazole 400 mg. for 7 days, starting immediately after the first session of Scaling and Root Planing.
Intervention Type
Drug
Intervention Name(s)
Metronidazole 250 (14 days)
Intervention Description
Subjects will intake Metronidazole 250 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.
Intervention Type
Drug
Intervention Name(s)
Metronidazole 400 (14 days)
Intervention Description
Subjects will intake Metronidazole 400 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.
Intervention Type
Drug
Intervention Name(s)
Amoxicillin
Intervention Description
Subjects will intake Amoxicillin 500 mg. for 14 days, starting immediately after and the first session of Scaling and Root Planing.
Intervention Type
Other
Intervention Name(s)
Placebo 250 (7 days)
Intervention Description
Subjects will intake placebo of Metronidazole 250 mg. for 7 days, starting immediately after to intake Metronidazole 250 mg.
Intervention Type
Other
Intervention Name(s)
Placebo 400 (7 days)
Intervention Description
Subjects will intake placebo of Metronidazole 400 mg. for 7 days, starting immediately after to intake Metronidazole 400 mg.
Intervention Type
Other
Intervention Name(s)
Placebo 400 (14 days)
Intervention Description
Subjects will intake placebo of Metronidazole 400 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.
Intervention Type
Other
Intervention Name(s)
Placebo 500
Intervention Description
Subjects will intake placebo of Amoxicillin 500 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.
Primary Outcome Measure Information:
Title
Percentage of subjects reaching ≤ 4 periodontal sites with probing depth (PD) ≥ 5 mm at 12 months
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Number of sites with PD ≥ 5 mm
Time Frame
Baseline, 3, 6 and 12 months
Title
Number of sites with PD ≥ 6 mm
Time Frame
Baseline, 3, 6 and 12 months
Title
Number of sites with PD ≥ 7 mm
Time Frame
Baseline, 3, 6 and 12 months
Title
Reduction in the number of sites with PD ≥ 5 mm
Time Frame
Baseline, 3, 6 and 12 months
Title
Reduction in the number of sites with PD ≥ 6 mm
Time Frame
Baseline, 3, 6 and 12 months
Title
Reduction in the number of sites with PD ≥ 7 mm
Time Frame
Baseline, 3, 6 and 12 months
Title
Full-mouth PD
Time Frame
Baseline, 3, 6 and 12 months
Title
Full-mouth clinical attachment level
Time Frame
Baseline, 3, 6 and 12 months
Title
Percentage of sites with bleeding on probing
Time Frame
Baseline, 3, 6 and 12 months
Title
Percentage of sites with plaque accumulation
Time Frame
Baseline, 3, 6 and 12 months
Title
Percentage of sites with marginal bleeding
Time Frame
Baseline, 3, 6 and 12 months
Title
Occurrence of headache obtained through a questionnaire of adverse effects
Time Frame
14 days after the beginning of treatments
Title
Occurrence of vomiting obtained through a questionnaire of adverse effects
Time Frame
14 days after the beginning of treatments
Title
Occurrence of diarrhea obtained through a questionnaire of adverse effects
Time Frame
14 days after the beginning of treatments
Title
Occurrence of metallic taste obtained through a questionnaire of adverse effects
Time Frame
14 days after the beginning of treatments
Title
Occurrence of nausea obtained through a questionnaire of adverse effects
Time Frame
14 days after the beginning of treatments
Title
Occurrence of irritability obtained through a questionnaire of adverse effects
Time Frame
14 days after the beginning of treatments
Title
Proportions of periodontal pathogenic bacterial species
Time Frame
Baseline, 3, 6 and 12 months
Title
Counts of periodontal pathogenic bacterial species
Time Frame
Baseline, 3, 6 and 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Magda Feres, Professor
Organizational Affiliation
Guarulhos University
Official's Role
Study Chair
Facility Information:
Facility Name
Guarulhos University
City
Guarulhos
State/Province
São Paulo
ZIP/Postal Code
07023-070
Country
Brazil
12. IPD Sharing Statement
Citations:
PubMed Identifier
22220822
Citation
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.
Results Reference
background
PubMed Identifier
15560807
Citation
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.
Results Reference
background
PubMed Identifier
19254119
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.
Results Reference
background
PubMed Identifier
25494600
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.
Results Reference
background
PubMed Identifier
23016867
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.
Results Reference
background
PubMed Identifier
16174275
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. doi: 10.1111/j.1600-051X.2005.00814.x.
Results Reference
background
PubMed Identifier
22882646
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.
Results Reference
background
PubMed Identifier
20447259
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.
Results Reference
background
PubMed Identifier
24930639
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.
Results Reference
background
PubMed Identifier
26087839
Citation
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.
Results Reference
background
PubMed Identifier
22220767
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. doi: 10.1902/jop.2012.110625. Epub 2012 Feb 14.
Results Reference
background
PubMed Identifier
22050545
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.
Results Reference
background
PubMed Identifier
21762197
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.
Results Reference
background
PubMed Identifier
26928597
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.
Results Reference
background
PubMed Identifier
22612369
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.
Results Reference
background
PubMed Identifier
24834504
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. doi: 10.1111/jcpe.12217.
Results Reference
background
PubMed Identifier
33197289
Citation
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.
Results Reference
derived
PubMed Identifier
28303587
Citation
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.
Results Reference
derived
Learn more about this trial
Dose and Duration of Metronidazole and Amoxicillin for Treatment of Chronic Periodontitis
We'll reach out to this number within 24 hrs