Amoxicillin and Metronidazole During Periodontal Treatment

NCT ID: NCT02954393

Last Updated: 2020-01-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

180 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-05-31

Study Completion Date

2020-12-31

Brief Summary

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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.

Detailed Description

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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%.

Conditions

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Chronic Periodontitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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Control

Scaling and root planing + Placebos active phase thrice a day (TID) for 14 days and Placebos healing phase TID for 14 days.

Group Type PLACEBO_COMPARATOR

Scaling and root planing

Intervention Type PROCEDURE

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.

Placebos active phase

Intervention Type DRUG

Amoxicillin and metronidazole placebos thrice a day for 14 days in the active phase (beginning with the first SRP session).

Placebos healing phase

Intervention Type DRUG

Amoxicillin and metronidazole placebos thrice a day for 14 days in the healing phase (3 months after active phase).

Active phase

Scaling and root planing + Metronidazole active phase (400 mg/thrice a day,TID) + Amoxicillin active phase (500 mg/ TID) for 14 days and Placebos healing phase TID for 14 days.

Group Type ACTIVE_COMPARATOR

Scaling and root planing

Intervention Type PROCEDURE

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.

Metronidazole active phase

Intervention Type DRUG

Metronidazole 400 mg thrice a day for 14 days in the active phase of the periodontal treatment (beginning with the first SRP session).

Amoxicillin active phase

Intervention Type DRUG

Amoxicillin 500 mg thrice a day for 14 days in the active phase of the periodontal treatment (beginning with the first SRP session).

Placebos healing phase

Intervention Type DRUG

Amoxicillin and metronidazole placebos thrice a day for 14 days in the healing phase (3 months after active phase).

Healing phase

Scaling and root planing + Placebos active phase thrice a day (TID) for 14 days and Metronidazole healing phase (400 mg/TID) + Amoxicillin healing phase (500 mg/TID) for 14 days.

Group Type ACTIVE_COMPARATOR

Scaling and root planing

Intervention Type PROCEDURE

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.

Metronidazole healing phase

Intervention Type DRUG

Metronidazole 400 mg thrice a day for 14 days in the healing phase of the periodontal treatment (3 months after active phase).

Amoxicillin healing phase

Intervention Type DRUG

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

Intervention Type DRUG

Amoxicillin and metronidazole placebos thrice a day for 14 days in the active phase (beginning with the first SRP session).

Interventions

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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.

Intervention Type PROCEDURE

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).

Intervention Type DRUG

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).

Intervention Type DRUG

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).

Intervention Type DRUG

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).

Intervention Type DRUG

Placebos active phase

Amoxicillin and metronidazole placebos thrice a day for 14 days in the active phase (beginning with the first SRP session).

Intervention Type DRUG

Placebos healing phase

Amoxicillin and metronidazole placebos thrice a day for 14 days in the healing phase (3 months after active phase).

Intervention Type DRUG

Other Intervention Names

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SRP MTZ 1 MTZ 2 AMX 1 AMX 2 P 1 P 2

Eligibility Criteria

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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.
Minimum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Belén Retamal-Valdes

OTHER

Sponsor Role lead

Responsible Party

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Belén Retamal-Valdes

DDS, MSc, PhD Student

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Magda Feres, Professor

Role: STUDY_CHAIR

University of Guarulhos

Locations

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University of Guarulhos

Guarulhos, São Paulo, Brazil

Site Status

University of São Paulo

São Paulo, , Brazil

Site Status

Countries

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Brazil

References

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Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol. 1999 Dec;4(1):1-6. doi: 10.1902/annals.1999.4.1.1.

Reference Type BACKGROUND
PMID: 10863370 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23016867 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25494600 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18279183 (View on PubMed)

Herrera D, Sanz M, Jepsen S, Needleman I, Roldan 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. doi: 10.1034/j.1600-051x.29.s3.8.x.

Reference Type BACKGROUND
PMID: 12787214 (View on PubMed)

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.

Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 15643744 (View on PubMed)

Matuliene G, Pjetursson BE, Salvi GE, Schmidlin K, Bragger 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.

Reference Type BACKGROUND
PMID: 18549447 (View on PubMed)

Matuliene G, Studer R, Lang NP, Schmidlin K, Pjetursson BE, Salvi GE, Bragger 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.

Reference Type BACKGROUND
PMID: 20041980 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20447259 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22882646 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22220767 (View on PubMed)

Socransky SS, Haffajee AD. Dental biofilms: difficult therapeutic targets. Periodontol 2000. 2002;28:12-55. doi: 10.1034/j.1600-0757.2002.280102.x. No abstract available.

Reference Type BACKGROUND
PMID: 12013340 (View on PubMed)

Socransky SS, Haffajee AD. Periodontal microbial ecology. Periodontol 2000. 2005;38:135-87. doi: 10.1111/j.1600-0757.2005.00107.x. No abstract available.

Reference Type BACKGROUND
PMID: 15853940 (View on PubMed)

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. doi: 10.1111/j.1600-051x.1998.tb02419.x.

Reference Type BACKGROUND
PMID: 9495612 (View on PubMed)

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. doi: 10.1111/j.1600-051x.1991.tb00070.x.

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

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Teles RP, Haffajee AD, Socransky SS. Microbiological goals of periodontal therapy. Periodontol 2000. 2006;42:180-218. doi: 10.1111/j.1600-0757.2006.00192.x. No abstract available.

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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.

Reference Type DERIVED
PMID: 33197289 (View on PubMed)

Feres M, Retamal-Valdes B, Mestnik MJ, de Figueiredo LC, Faveri M, Duarte PM, Fritoli A, Faustino E, Souto MLS, de Franco Rodrigues M, Giudicissi M, Nogueira BCL, Saraiva L, Romito GA, Pannuti CM. The ideal time of systemic metronidazole and amoxicillin administration in the treatment of severe periodontitis: study protocol for a randomized controlled trial. Trials. 2018 Mar 27;19(1):201. doi: 10.1186/s13063-018-2540-8.

Reference Type DERIVED
PMID: 29587808 (View on PubMed)

Other Identifiers

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CAAE: 32465714.4.1001.5506

Identifier Type: -

Identifier Source: org_study_id

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