Dose and Duration of Metronidazole and Amoxicillin for Treatment of Chronic Periodontitis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Impact of Different Dosages and Time of Administration of Metronidazole and Amoxicillin in the Treatment of Generalized Chronic Periodontitis: A Randomized Clinical Trial

Conditions
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Chronic Periodontitis

Intervention / Treatment
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* Procedure: Scaling and root planing (SRP)
* Drug: Metronidazole 250 (7 days)
* Drug: Metronidazole 400 (7 days)
* Drug: Metronidazole 250 (14 days)
* Drug: Metronidazole 400 (14 days)
* Drug: Amoxicillin
* Other: Placebo 250 (7 days)
* Other: Placebo 400 (7 days)
* Other: Placebo 400 (14 days)
* Other: Placebo 500


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 30 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br>Scaling and root planing (SRP) + two placebo pills thrice a day (TID) for 14 days (control group) | Procedure: Scaling and root planing (SRP)<br>* 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.<br>Other: Placebo 400 (14 days)<br>* Subjects will intake placebo of Metronidazole 400 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.<br>Other: Placebo 500<br>* Subjects will intake placebo of Amoxicillin 500 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.<br>|
| Active Comparator: MTZ 250 (7 days)<br>SRP + MTZ (250mg/TID) + AMX, for 7 days and placebos for another 7 days | Procedure: Scaling and root planing (SRP)<br>* 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.<br>Drug: Metronidazole 250 (7 days)<br>* Subjects will intake Metronidazole 250 mg. for 7 days, starting immediately after the first session of Scaling and Root Planing.<br>Drug: Amoxicillin<br>* Subjects will intake Amoxicillin 500 mg. for 14 days, starting immediately after and the first session of Scaling and Root Planing.<br>Other: Placebo 250 (7 days)<br>* Subjects will intake placebo of Metronidazole 250 mg. for 7 days, starting immediately after to intake Metronidazole 250 mg.<br>|
| Active Comparator: MTZ 400 (7 days)<br>SRP + MTZ (400mg/TID) + AMX, for 7 days and placebos for another 7 days | Procedure: Scaling and root planing (SRP)<br>* 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.<br>Drug: Metronidazole 400 (7 days)<br>* Subjects will intake Metronidazole 400 mg. for 7 days, starting immediately after the first session of Scaling and Root Planing.<br>Drug: Amoxicillin<br>* Subjects will intake Amoxicillin 500 mg. for 14 days, starting immediately after and the first session of Scaling and Root Planing.<br>Other: Placebo 400 (7 days)<br>* Subjects will intake placebo of Metronidazole 400 mg. for 7 days, starting immediately after to intake Metronidazole 400 mg.<br>|
| Active Comparator: MTZ 250 (14 days)<br>SRP +MTZ (250mg/TID) + AMX for 14 days | Procedure: Scaling and root planing (SRP)<br>* 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.<br>Drug: Metronidazole 250 (14 days)<br>* Subjects will intake Metronidazole 250 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.<br>Drug: Amoxicillin<br>* Subjects will intake Amoxicillin 500 mg. for 14 days, starting immediately after and the first session of Scaling and Root Planing.<br>|
| Active Comparator: MTZ 400 (14 days)<br>SRP +MTZ (400mg/TID) + AMX for 14 days | Procedure: Scaling and root planing (SRP)<br>* 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.<br>Drug: Metronidazole 400 (14 days)<br>* Subjects will intake Metronidazole 400 mg. for 14 days, starting immediately after the first session of Scaling and Root Planing.<br>Drug: Amoxicillin<br>* Subjects will intake Amoxicillin 500 mg. for 14 days, starting immediately after and the first session of Scaling and Root Planing.<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 at 12 months |  | 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 | 
| 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 the beginning of treatments | 
| Occurrence of vomiting obtained through a questionnaire of adverse effects |  | 14 days after the beginning of treatments | 
| Occurrence of diarrhea obtained through a questionnaire of adverse effects |  | 14 days after the beginning of treatments | 
| Occurrence of metallic taste obtained through a questionnaire of adverse effects |  | 14 days after the beginning of treatments | 
| Occurrence of nausea obtained through a questionnaire of adverse effects |  | 14 days after the beginning of treatments | 
| Occurrence of irritability obtained through a questionnaire of adverse effects |  | 14 days after the beginning of treatments | 
| 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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Periodontal Diseases, Metronidazole, Amoxicillin, Chronic periodontitis, Root Planing