Amoxicillin and Metronidazole During or After the Periodontal Treatment

Periodontitis Clinical Trial

Official title:

Timing of Administration of Systemic Antibiotics Associated With Scaling and Root Planing in the Treatment of Periodontitis: Clinical and Microbiological Evaluation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06177119
• Other study ID #: SISNEP/726_Jan31_2012
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 31, 2012
• Est. completion date: December 31, 2024

Study information

• Verified date: December 2023
• Source: University of Guarulhos
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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%.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 72
• Est. completion date: December 31, 2024
• Est. primary completion date: July 1, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Periodontitis

Intervention

Procedure:
• 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.

Drug:
• Placebos during SRP
Amoxicillin and metronidazole placebos thrice a day for 14 days, beginning with the first SRP session.
• Placebos after SRP
Amoxicillin and metronidazole placebos thrice a day for 14 days, beginning after the last SRP session.
• Metronidazole during SRP
Metronidazole 400 mg, thrice a day for 14 days, beginning with the first SRP session.
• Amoxicillin during SRP
Amoxicillin 500 mg, thrice a day for 14 days, beginning with the first SRP session.
• Metronidazole after SRP
Metronidazole 400 mg, thrice a day for 14 days, beginning after the last SRP session.
• Amoxicillin after SRP
Amoxicillin 500 mg, thrice a day for 14 days, beginning after the last SRP session.

Locations

Country	Name	City	State
Brazil	University of Guarulhos	Guarulhos	Sao Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Belén Retamal-Valdes

Country where clinical trial is conducted

Brazil, 

References & Publications (10)

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/j — View Citation

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. — View Citation

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. N — 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. — View Citation

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. — View Citation

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: — 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 clinic — View Citation

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. — 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 — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of subjects reaching = 4 periodontal sites with probing depth (PD) = 5 mm.		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	Mean PD changes in sites with initial PD between 4-6 mm		Baseline - 12 months.
Secondary	Mean PD changes in sites with initial PD = 7 mm.		Baseline - 12 months.
Secondary	Mean CAL changes in sites with initial CAL between 4-6 mm ,		Baseline - 12 months.
Secondary	Mean CAL changes in sites with initial CAL = 7 mm.		Baseline - 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 taking antibiotic.
Secondary	Occurrence of vomiting obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Occurrence of diarrhea obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Occurrence of metallic taste obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Occurrence of nausea obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Occurrence of irritability obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
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.