Amoxicillin and Metronidazole During or After the Periodontal Treatment

Study Overview
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Brief Summary
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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
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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%.

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

Conditions
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Periodontitis

Intervention / Treatment
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* Procedure: Scaling and root planing
* Drug: Placebos during SRP
* Drug: Placebos after SRP
* Drug: Metronidazole during SRP
* Drug: Amoxicillin during SRP
* Drug: Metronidazole after SRP
* Drug: Amoxicillin after SRP


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test 1<br>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 | Procedure: Scaling and root planing<br>* 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.<br>* Other names: SRP;Drug: Placebos after SRP<br>* Amoxicillin and metronidazole placebos thrice a day for 14 days, beginning after the last SRP session.<br>Drug: Metronidazole during SRP<br>* Metronidazole 400 mg, thrice a day for 14 days, beginning with the first SRP session.<br>Drug: Amoxicillin during SRP<br>* Amoxicillin 500 mg, thrice a day for 14 days, beginning with the first SRP session.<br>|
| Experimental: Test 2<br>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. | Procedure: Scaling and root planing<br>* 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.<br>* Other names: SRP;Drug: Placebos during SRP<br>* Amoxicillin and metronidazole placebos thrice a day for 14 days, beginning with the first SRP session.<br>Drug: Metronidazole after SRP<br>* Metronidazole 400 mg, thrice a day for 14 days, beginning after the last SRP session.<br>Drug: Amoxicillin after SRP<br>* Amoxicillin 500 mg, thrice a day for 14 days, beginning after the last SRP session.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects reaching ≤ 4 periodontal sites with probing depth (PD) ≥ 5 mm. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| Reduction in the number of sites with PD ≥ 7 mm. |  | Baseline, 3, 6 and 12 months. | 
| Mean PD changes in sites with initial PD between 4-6 mm |  | Baseline - 12 months. | 
| Mean PD changes in sites with initial PD ≥ 7 mm. |  | Baseline - 12 months. | 
| Mean CAL changes in sites with initial CAL between 4-6 mm , |  | Baseline - 12 months. | 
| Mean CAL changes in sites with initial CAL ≥ 7 mm. |  | Baseline - 12 months. | 
| Full-mouth PD. |  | Baseline, 3, 6 and 12 months. | 
| Full-mouth clinical attachment level. |  | Baseline, 3, 6 and 12 months. | 
| Percentage of sites with bleeding on probing. |  | Baseline, 3, 6 and 12 months. | 
| Percentage of sites with plaque accumulation. |  | Baseline, 3, 6 and 12 months. | 
| Percentage of sites with marginal bleeding. |  | Baseline, 3, 6 and 12 months. | 
| Occurrence of headache obtained through a questionnaire of adverse effects. |  | 14 days after taking antibiotic. | 
| Occurrence of vomiting obtained through a questionnaire of adverse effects. |  | 14 days after taking antibiotic. | 
| Occurrence of diarrhea obtained through a questionnaire of adverse effects. |  | 14 days after taking antibiotic. | 
| Occurrence of metallic taste obtained through a questionnaire of adverse effects. |  | 14 days after taking antibiotic. | 
| Occurrence of nausea obtained through a questionnaire of adverse effects. |  | 14 days after taking antibiotic. | 
| Occurrence of irritability obtained through a questionnaire of adverse effects. |  | 14 days after taking antibiotic. | 
| Proportions of periodontal pathogenic bacterial species. |  | Baseline, 3, 6 and 12 months. | 
| Counts of periodontal pathogenic bacterial species. |  | Baseline, 3, 6 and 12 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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periodontitis, scaling and root planing, metronidazole, amoxicillin, treatment, microbiota