Amoxicillin to Prevent Bacteria and Inflammatory Biomarkers After Intensive Periodontal Therapy

Study Overview
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Brief Summary
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There are not published studies evaluating the incidence, nature, magnitude and/or duration of bacteremia after periodontal treatment. The pre-surgical antibiotics have been studied particullary over Gram positive bacterial but not over gram negative bacterial and their secondary effects over the systemic pro-inflamation. Objective: to evaluate the efficacy of intensive periodontal therapy and pre-medication with oral amoxicilline on inflammatory bio-markers and the incidence, duration and magnitude of bacteremia in patients with chronic periodontitis.

Detailed Description
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A randomized, triple-blind clinical trial with 90 participants will be conducted (age range18-65 years) with chronic periodontitis will be received and intensive periodontal therapy under local anaesthesia. Participants will be randomly assigned using block randomization in two groups. Test group premedication with 2 gr of oral amoxicilline 1 hour before periodontal treatment and control group with 2 gr of placebo 1 hour before treatment. High-sensitivity assays will be used to quantify serum concentrations of inflammatory marker (Interleukin (IL-1β), Interleukin 6, Tumour necrosis factor α, MCP 1, C Reactive Protein (CRP), plasma haemostatic (D-dimer), and von Willebrand factor antigen (r-WF:Ag). Samples of blood will be taken at baseline (before treatment), inmediatly finished the treatment, 30 minutes and 1, seven and 30 days after treatment to asses bacteremia and inflammatory markers. Bacterial isolation and identification: Bacterial colonies will be isolated on both selective and nonselective culture medium for aerobes and anaerobes bacteria. Sensitive Digital quantitative polymerase chain reaction will be used to quantify bacteria. Concentrations of CPRus, inflammatory, haemostatic and endotellial cell activation markers will be quantified by high-sensitive enzyme liked inmunosorbent assays according to the manufacturer´s protocol. For each cytokine, comparisons between groups will be made by time. The levels of cytokines expressed in picograms will be transformed into international units for the statistical analysis. In case it follows a normal distribution, an analysis of variance (ANOVA) for repeated measurements between groups with post hoc corrections made by Wilcoxon test will be used. In case it doesn´t follow a normal distribution, Non parametric test such as Friedman´s test will be used. Values of p<0.05 will be accepted as statiscally significant.

Official Title
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Efficacy of Intensive Periodontal Therapy and Premedication With Oral Amoxicilline on Inflammatory Markers and Bacteremia in Patients With Chronic Periodontitis. A Randomized Controlled Trial.

Conditions
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Chronic Periodontitis, Bacteremia

Intervention / Treatment
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* Drug: Amoxicillin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with chronic periodontitis (Ameriacam Academy of Periodontology 2015), having at least 2 teeth for quadrant with periodontal probing pockets depth ≥ 5 mm. Exclusion Criteria: Pregnant and lactating women, Diabetes, hypertension, Obesity, Allergy to penicillin, consumption of systemic antimicrobial or anti-inflamatory drugs in the last 2 months, Autoimmune diseases, patients with medical conditions that required antibiotic premedication such as prosthetic heart valve replacement, skeletal joint replacement, previous history of infective endocarditis and history of rheumatic fever.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: A triple-blind randomized controlled trial with 90 participants will be conducted. Participants will be assigned using block randomization in two groups and will received intensive periodontal therapy under local anaesthesia. Test group pre-medication with 2 gr of oral amoxicilline 1 hour before treatment. Control group with 2 gr of placebo 1 hour before treatment. Samples of blood will be taken at baseline (before treatment), immediately finished the treatment, 30 minutes later, after 24 hours, after seven days and on the day 30th to asses bacteremia and inflammatory markers
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>Intensive Periodontal treatment and pre-medication with 2 gr of oral amoxicilline 1 hour before treatment | Drug: Amoxicillin<br>* Intensive Periodontal treatment; Pre-medication with 2 gr of oral Amoxicillin 1 hour before treatment<br>* Other names: Intensive Periodontal treatment;|
| Placebo Comparator: PLACEBO<br>Intensive Periodontal treatment with 2 gr of Placebo 1 hour before treatment | Other: Placebo<br>* Intensive Periodontal treatment; Pre-medication with 2 gr of Placebo 1 hour before treatment<br>* Other names: Intensive Periodontal treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence bacteria Change | absence or presence bacterial in blood | baseline (before treatment), immediately finished the treatment, 30 minutes later, after 24 hours, after seven days and on the day 30th | 
| Change of Nature of the bacteria | bacterial strain | baseline (before treatment), immediately finished the treatment, 30 minutes later, after 24 hours, after seven days and on the day 30th | 
| Change of magnitude of bacteremia | Colony forming units (CFU) | baseline (before treatment), immediately finished the treatment, 30 minutes later, after 24 hours, after seven days and on the day 30th | 
| Duration of bacteremia | Bacteremia´s minutes | baseline (before treatment), immediately finished the treatment, 30 minutes later, after 24 hours, after seven days and on the day 30th | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of levels of Interleukin | Levels pg/ml | baseline, immediately finished the treatment, 30 minutes, 24 hours, 7 days and day 30th later | 
| Change of C Reactive Protein (CRP) | Levels mg/L | baseline, immediately finished the treatment, 30 minutes, 24 hours, 7 days and day 30th later | 
| Change of levels of plasma haemostatic (D-dimer) | Levels ng/ml | baseline, immediately finished the treatment, 30 minutes, 24 hours, 7 days and day 30th later | 
| Change of von Willebrand factor antigen (r-WF:Ag) | Levels ng/ml | baseline, immediately finished the treatment, 30 minutes, 24 hours, 7 days and day 30th later | 
| Change of Pressure blood | Millimeter of mercury (mmHg) | baseline, immediately finished the treatment | 
| Change of Heart rate. | Beats per Minute (BPM) | baseline, immediately finished the treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Periodontal disease, Bacteremia, Amoxicilline, Inflamatory markers