Amoxicillin and Metronidazole During or After the Periodontal Treatment

NCT ID: NCT06177119

Last Updated: 2023-12-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2024-12-31

Brief Summary

This randomized clinical trial aimed to compare the clinical and microbiological effects of different times of administration of metronidazole (MTZ) and amoxicillin (AMX) in the treatment of periodontitis.

Detailed Description

Scaling and root planing (SRP) is the most used periodontal therapy for periodontal treatment. Despite leading, in most cases, to an improvement in periodontal clinical parameters, SRP is often insufficient to profoundly modify the pathogenic bacterial profile to a profile related to periodontal health, especially in cases of more advanced and generalized diseases. Thus, other therapies supporting SRP, such as systemic antibiotics, have been proposed with the aim of enhancing the clinical and microbiological effects of this form of therapy. Studies have shown excellent clinical and microbiological results using the association of systemic antibiotics, especially the association of metronidazole (MTZ) and amoxicillin (AMX) in the treatment of severe periodontitis. However, some essential issues associated with the use of these antibiotics remain to be established. Therefore, the aim of this randomized clinical trial was to compare the clinical and microbiological effects of different times of administration of metronidazole (MTZ) and amoxicillin (AMX) in the treatment of periodontitis. Seventy-two subjects with severe periodontitis were selected and randomized into two groups (n = 36 / group) - Test 1 (T1): SRP in 14 days, associated with the concomitant use of AMX (500mg, 3x / day) and MTZ (400mg 3x / day) for 14 days; and Test 2 (T2): SRP in 14 days, associated with the use of AMX and MTZ immediately after the end of the SRP in the following 14 days. All volunteers received clinical and microbiological evaluation at baseline, 3, 6 and 12 months post-SRP. Subgingival biofilm samples were collected by subject and analyzed for counts and proportions of 40 bacterial species by checkerboard DNA-DNA hybridization. Differences in clinical and microbiological parameters between groups and over time were evaluated using the ANOVA, ANCOVA, Chi-square and Tukey tests. Microbiological analyzes were performed using adjustments for multiple comparisons. Statistical significance was set at 5%.

Conditions

Periodontitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Test 1

Scaling and root planing + Metronidazole (400 mg/thrice a day,TID) and Amoxicillin (500 mg/ TID) for 14 days, starting with the first SRP session

Group Type: EXPERIMENTAL

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 after SRP

Intervention Type: DRUG

Amoxicillin and metronidazole placebos thrice a day for 14 days, beginning after the last SRP session.

Metronidazole during SRP

Intervention Type: DRUG

Metronidazole 400 mg, thrice a day for 14 days, beginning with the first SRP session.

Amoxicillin during SRP

Intervention Type: DRUG

Amoxicillin 500 mg, thrice a day for 14 days, beginning with the first SRP session.

Test 2

Scaling and root planing (SRP) + Metronidazole (400 mg/thrice a day,TID) and Amoxicillin (500 mg/ TID) immediately after the end of the SRP in the following 14 days.

Group Type: EXPERIMENTAL

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 during SRP

Intervention Type: DRUG

Amoxicillin and metronidazole placebos thrice a day for 14 days, beginning with the first SRP session.

Metronidazole after SRP

Intervention Type: DRUG

Metronidazole 400 mg, thrice a day for 14 days, beginning after the last SRP session.

Amoxicillin after SRP

Intervention Type: DRUG

Amoxicillin 500 mg, thrice a day for 14 days, beginning after the last SRP session.

Interventions

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

Placebos during SRP

Amoxicillin and metronidazole placebos thrice a day for 14 days, beginning with the first SRP session.

Intervention Type: DRUG

Placebos after SRP

Amoxicillin and metronidazole placebos thrice a day for 14 days, beginning after the last SRP session.

Intervention Type: DRUG

Metronidazole during SRP

Metronidazole 400 mg, thrice a day for 14 days, beginning with the first SRP session.

Intervention Type: DRUG

Amoxicillin during SRP

Amoxicillin 500 mg, thrice a day for 14 days, beginning with the first SRP session.

Intervention Type: DRUG

Metronidazole after SRP

Metronidazole 400 mg, thrice a day for 14 days, beginning after the last SRP session.

Intervention Type: DRUG

Amoxicillin after SRP

Amoxicillin 500 mg, thrice a day for 14 days, beginning after the last SRP session.

Intervention Type: DRUG

Other Intervention Names

SRP

Eligibility Criteria

Inclusion Criteria

• 18 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 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: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Belén Retamal-Valdes

OTHER

Sponsor Role: lead

Responsible Party

Belén Retamal-Valdes

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Marcelo Faveri, Professor

Role: STUDY_CHAIR

University of Guarulhos

Locations

University of Guarulhos

Guarulhos, São Paulo, Brazil

Countries

Brazil

References

Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, Flemmig TF, Garcia R, Giannobile WV, Graziani F, Greenwell H, Herrera D, Kao RT, Kebschull M, Kinane DF, Kirkwood KL, Kocher T, Kornman KS, Kumar PS, Loos BG, Machtei E, Meng H, Mombelli A, Needleman I, Offenbacher S, Seymour GJ, Teles R, Tonetti MS. Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Clin Periodontol. 2018 Jun;45 Suppl 20:S162-S170. doi: 10.1111/jcpe.12946.

Reference Type: BACKGROUND

PMID: 29926490 (View on PubMed)

Feres M, Retamal-Valdes B, Faveri M, Duarte P, Shibli J, Soares GMS, Miranda T, Teles F, Goodson M, Hasturk H, Van Dyke T, Ehmke B, Eickholz P, Schlagenhauf U, Meyle J, Koch R, Kocher T, Hoffmann T, Kim TS, Kaner D, Figueiredo LC, Doyle H. Proposal of a Clinical Endpoint for Periodontal Trials: The Treat-to-Target Approach. J Int Acad Periodontol. 2020 Apr 1;22(2):41-53.

Reference Type: BACKGROUND

PMID: 32224549 (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: RESULT

PMID: 25494600 (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: RESULT

PMID: 23016867 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24834504 (View on PubMed)

Faveri M, Figueiredo LC, Feres M. Treatment of chronic periodontitis may be improved by the adjunctive use of systemic metronidazole. J Evid Based Dent Pract. 2014 Jun;14(2):70-2. doi: 10.1016/j.jebdp.2014.04.025. Epub 2014 Apr 12. No abstract available.

Reference Type: RESULT

PMID: 24913531 (View on PubMed)

Feres M, Faveri M, Figueiredo LC, Teles R, Flemmig T, Williams R, Lang NP. Group B. Initiator paper. Non-surgical periodontal therapy: mechanical debridement, antimicrobial agents and other modalities. J Int Acad Periodontol. 2015 Jan;17(1 Suppl):21-30. No abstract available.

Reference Type: RESULT

PMID: 25764587 (View on PubMed)

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.

Reference Type: RESULT

PMID: 28303587 (View on PubMed)

Teughels W, Feres M, Oud V, Martin C, Matesanz P, Herrera D. Adjunctive effect of systemic antimicrobials in periodontitis therapy: A systematic review and meta-analysis. J Clin Periodontol. 2020 Jul;47 Suppl 22:257-281. doi: 10.1111/jcpe.13264.

Reference Type: RESULT

PMID: 31994207 (View on PubMed)

Feres M, Retamal-Valdes B, Fermiano D, Faveri M, Figueiredo LC, Mayer MPA, Lee JJ, Bittinger K, Teles F. Microbiome changes in young periodontitis patients treated with adjunctive metronidazole and amoxicillin. J Periodontol. 2021 Apr;92(4):467-478. doi: 10.1002/JPER.20-0128. Epub 2020 Oct 12.

Reference Type: RESULT

PMID: 32844406 (View on PubMed)

Other Identifiers

SISNEP/726_Jan31_2012

Identifier Type: -

Identifier Source: org_study_id