Metronidazole as an Adjunct of Non- Surgical Treatment of Peri-implantitis

Study Overview
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Brief Summary
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The use of systemic antibiotics as and adjunct to non-surgical peri-implant therapy may be an improvement in comparison to these therapies alone. The primary objective is the evaluation of significant changes in probing pocket depth between non-surgical with or without antibiotics. This is a controlled-placebo clinical trial design. Patients with osseointegrated oral implants will be selected and recruited from a university clinic. Oral hygiene instruction and non-surgical debridement at implants will be provided with ultrasonic devices and immediately after, patients will be prescribed: Group Control: A placebo with the same characteristics as the antibiotic Group Test: Systemic antibiotics (Metronidazole 250mg, 2 capsules three times a day, for 7 days Three and six months after non-surgical treatment, clinical parameters will be registered and radiographs compared using reproducible landmarks. Any adverse event will be also recorded.

Detailed Description
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Microbial colonization of implant surface is the main causative factor of periimplantitis. Non-surgical treatment have been shown to be ineffective in bacterial control. The capacity of certain bacteria to invade soft tissues in periodontal lesions and a possible invasion in peri-implant diseases, could also be a good reason. Mombelli and Lang in a case-series study observed a significant reduction on probing depths and microbial parameters after non-surgical treatment and systemic antimicrobial therapy (ornidazole) of implants affected by marked loss of bone. The rationale for conducting this research is to demonstrate that there may be significant differences in clinical, radiographic and microbiological parameters if systemic metronidazole is prescribed in conjunction with non-surgical treatment of peri-implantitis lesions. If there are differences, and a further improvement is observed in evaluated parameters, treatment protocols for these prevalent lesions could have been modified. The objective of this research is to check whether there are differences in clinical, radiographic and microbiological parameters when performing non-surgical treatment to treat peri-implantitis with adjunctive administration of systemic metronidazole or a placebo. Design: This research is designed as a parallel group, placebo-controlled, randomized, double-blind clinical study. Population: Patients who come to the Periodontology Department, Faculty of Dentistry, University of Santiago de Compostela with dental implants presenting pathology. Treatment Groups: Study group: patients treated by non-surgical treatment in conjunction with systemic metronidazole.Control group: patients treated by non-surgical treatment in conjunction with a placebo. Randomization:After checking the inclusion criteria, signing the informed consent and included in the study. All subjects will be randomly assigned a number and one of the treatment group. The randomization will be done by a computer program for a simple randomization assignment. Treatment: Non-surgical treatments will be performed under local anaesthesia . In cases where the prosthesis is screwed and screw access is possible, it will be removed during treatment and re-placed once completed. The patient will rinse with a mouthwash of chlorhexidine digluconate 0.12% and then implants affected will be debrided by ultrasound and manual curettes with the objective of removing deposits of plaque and calculus that are attached to the surface of the implant or prosthesis. Once the debridement is finished, pockets will be irrigated with chlorhexidine for 2 minutes and the surface of the prostheses polished using rubber cups and polishing paste.Immediately after the end of treatment and depending on the result of randomization, the exact number of tablets of the antibiotic or placebo to be taken during the following days will be given to the patient. The patient will be instructed in oral hygiene with either manual or electric toothbrush and interdental hygiene at the time of the completion of treatment. Subsequently, at 4 weeks, motivation and hygiene instructions will be strengthened by modifying brushing technique when deemed necessary.

Official Title
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Metronidazole as an Adjunct of Non- Surgical Treatment of Peri-implantitis : a 6-months Placebo- Controlled Clinical Trial in Humans

Conditions
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Peri-Implantitis

Intervention / Treatment
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* Drug: Placebo oral capsule
* Drug: Metronidazole 250 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Older than 18 years. Presence of at least 1 implant diagnosed with peri-implantitis (Presence of BOP and/or suppuration, with 2 mm of detectable bone loss after initial remodeling, and PD≥ 4 mm as defined by Daubert et al. 2015). Absence of implant mobility. History of taking systemic antibiotics in the preceding 3 months. No systemic pathology that contraindicated the completion of treatment. The patient understands the treatment and willing to comply. The patient is willing to give written informed consent and can do Exclusion Criteria: Pregnant. Metronidazole allergies Patients on treatment with bisphosphonates. Uncontrolled periodontal disease.

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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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: PLACEBO-CONTROLLED CLINICAL TRIAL IN HUMAN
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metronidazole 250mg<br>Systemic antibiotic: Metronidazole 250mg , 2 capsules three times a day, for 7 days. | Drug: Metronidazole 250 MG<br>* Immediately after the end of non surgical treatment of periimplantitis and depending on the result of randomization, the exact number of tablets of the antibiotic to be taken during the following days will be given to the patient.<br>|
| Placebo Comparator: Placebo<br>Placebo: same shape, size and dosis as test | Drug: Placebo oral capsule<br>* Immediately after the end of non surgical treatment of periimplantitis and depending on the result of randomization, the exact number of tablets of the placebo to be taken during the following days will be given to the patient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in probing depth | Probing depth is the distance from the gingival margin to the bottom of the periodontal pocket (junctional epithelium). It is measured with a millimetric probe CP15 Hu-Friedy UNC at six points in each implant (mesial, distal and medial in buccal and lingual). | baseline, 2 and 6 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recession | the distance is measured from the free gingival margin (more coronal portion of the free gingiva) to the cement enamel junction. The following values are obtained: Zero: if the level of the cement enamel junction. Negative: the free gingival margin is apical to the cement enamel junction. Positive: when the free gingival margin is coronal to the cement enamel junction. | baseline, 2 and 6 months after treatment | 
| Attachment level | Distance from the cement enamel junction to the bottom of the periodontal pocket (probing depth + recession). | baseline, 2 and 6 months after treatment | 
| Bleeding Index | it will be recorded in six locations per tooth. It will be registered as presence or absence. If bleed- ing occured within 10-15 s, a positive score will be given. | baseline, 2 and 6 months after treatment | 
| Peri-implant bone loss. | Distance from the implant shoulder to the first bone-implant contact in mesial and distal aspects of each implant.. The extent of peri-implant bone loss will be performed with Kodak® software and a correction of the vertical distortion of the x- rays will be done by the technique described by Tonetti et al. (1993). | baseline, 2 and 6 months after treatment | 
| Microbiological variable | in terms of presence of periodontal pathogens and bacterial load. Deeper locations around each implant will be selected. The samples will be analyzed by real-time PCR. It will be recorded as the total percentage of each bacterium | baseline and 6 months after treatment | 
| plaque index | it will be recorded in four locations per tooth. It will be registered as presence or absence. Plaque present along the gingival margin that could be easily removed with the tip of a probe was recorded. Percentage scores for the presence of plaque over all examined sites will be calculated for each patient. | baseline, 2 and 6 months after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peri-implantitis, antibiotics, Metronidazole, non- surgical treatment