Two Different Antibiotic Agents to Treat Generalized Aggressive Periodontitis

Full-mouth Periodontal Debridement Associated With Two Different Antibiotic Agents to Treat Generalized Aggressive Periodontitis: Randomized Controlled Clinical Trial

The aim of this study is to assess the clinical outcomes of full-mouth ultrasonic debridement combined with clarithromycin or amoxicillin + metronidazole association for the treatment of generalized aggressive periodontitis (GAgP).

Study Overview

• Status: Completed
• Conditions: Aggressive Periodontitis
• Intervention / Treatment: Procedure: Full-mouth ultrasonic debridement; Drug: Amoxicillin; Drug: Metronidazole; Drug: Clarithromycin

Detailed Description

The study methodology is according to CONSORT-STATEMENT 2010 for randomized controlled clinical trials.

Study Design

The study is designed as a prospective, interventional, parallel, triple blind, randomized, controlled clinical trial aimed to assess the clinical outcomes of full-mouth ultrasonic debridement combined with clarithromycin or amoxicillin + metronidazole association for the treatment of generalized aggressive periodontitis (GAgP). The study was approved by Institute of Science and Technology's (ICT - State University of São Paulo) Ethics Committee (protocol 1.079.307).

Source of data

The population of this study will be recruited among patients referred to the Science and Technology Institute - ICT- São José dos Campos, College of Dentistry. Patients will fill a healthy history questionnaire to ensure that they are medically qualified for participate in this study. Based on the power calculation for this study, 44 subjects divided into two groups will be needed to achieve 80% power to detect a 0.8 mm difference in the clinical attachment level (CAL) of patients.

Clinical Parameters

All clinical parameters will be assessed by a single blinded, trained and calibrated examiner (CFA) before periodontal therapy (baseline) and at 3 and 6 months after using a manual probe. Measurements will be done at six sites per tooth (mesiobuccal, buccal, disto-buccal, distolingual, lingual, and mesiolingual) in all teeth, except third molars.

The following clinical parameters will be evaluated: 1) Full-mouth plaque index (FMPI); 2) Bleeding on probing (BoP); 3) Probing depth (PD): distance from the bottom of sulcus/pocket to gingival margin; 4) Gingival recession (GM): distance from the free gingival margin to cement-enamel junction (CEJ); 5) Clinical attachment level (CAL): distance from bottom of sulcus/pocket to the CEJ. The CEJ will be identified by careful probe on cervical area.

Calibration and Randomization

Initially, a total of ten patients presenting with GAgP will be selected. The designated examiner (CFA) will measure CAL and PD in all patients twice within 24 hours, with an interval of ≥ 1 hour between examinations. Then, the measures will be submitted to intraclass correlation test and the examiner will be judged calibrated if reaches 90% agreement.

Patients will be allocated into two groups according to a computer-generated list. The allocation will be implemented by an investigator (NCCS) who was not directly involved in the examination or treatment procedures. All medication will be prepared and encased in identical opaque coded bottles by a manipulation pharmacy on São José dos Campos/São Paulo.

Treatment Protocols

All patients will be treated with periodontal therapy through of the one-stage, full mouth, ultrasonic debridement (FMUD). In a single session, patients will receive local anesthesia and periodontal debridement with ultrasound equipment (Cavitron - Dentsply EUA) and subgingival tips (UI25KSF10S, Hu-Friedy). All diseased sites will be instrumented in this one session. The debridement session will be performed by a single experienced and trained periodontist (MPS), different from the examiner. Immediately before the mechanical therapy, patients will be allocated in one of the two treatment protocols:

1. Clarithromycin (CLM) group (n = 22): FMUD + CLM 500 mg bid, for 7 days and
2. Amoxicillin (AMX) + metronidazole (MET) group (n = 22): FMUD + (AMX 500 mg tid + MET 400 mg tid, both for 7 days.

All patients will start taking the pills immediately before of the FMUD session.

Compliance and Adverse Effects

After 7 days of periodontal treatment, patients will be asked to return any medication not taken and/or the empty bottles. The number of pills not taken by the subject will be documented. Moreover, patients will be instructed to return a self-report form filled about any possible adverse effects in order to help evaluate their adherence to the systemic antimicrobial regimen.

Statistical analysis

Mean and standard deviation will be calculated for each parameter. The normal distribution of the data will be analyzed by Shapiro-Wilk test. Data from clinical measurements will be subjected to analysis of variance (repeated measures) for inter and intra-group comparison.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Brazil
  • SP
    • São José dos Campos, SP, Brazil, 12245-310
      • College of Dentistry - São José dos Campos, São Paulo State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 33 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. diagnosis of GAgP (AAP, 1999);
2. presence of ≥20 teeth;
3. presence of ≥ 6 sites presenting PD ≥ 5mm with bleeding on probing (BOP) and ≥2 sites with PD ≥7mm (including incisors and first molars, in addition to other two non-contiguous teeth);
4. good general health;
5. ≤ 35 years old; and
6. agree to participate in the study and sign a written informed consent. All subjects will be individually informed about the objectives, probable risks and benefits of the protocol treatment (according to Resolution nº196 of October 1996 and to the Professional Code of Dental Ethics - 179/93).

Exclusion Criteria:

1. pregnancy or lactating;
2. suffer from any systemic disease (e.g. cardiovascular disorders, diabetes, blood dyscrasias, immunodeficiency, etc) which could alter the course of periodontal disease;
3. took antimicrobials in the previous 6 months;
4. taking long-term anti-inflammatory drugs;
5. previous periodontal treatment within the last 12 months;
6. smokers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Amoxicillin and Metronidazole; In this group (n = 23), patients will take Amoxicillin 500 mg tid for 7 days and Metronidazole 400 mg tid for 7 days and full-mouth ultrasonic debridement will be performed to treat diseased sites.	Procedure: Full-mouth ultrasonic debridement; Full-mouth ultrasonic debridement will be performed in order to treat diseased sites; Other Names: Periodontal debridement; Drug: Amoxicillin; Administration of Amoxicillin 500mg tid for 7 days.; Other Names: Amoxil; Drug: Metronidazole; Administration of Metronidazole 400mg tid for 7 days.; Other Names: Flagyl
Experimental: Clarithromycin; In this group (n = 23), patients will take Clarithromycin 500 mg bid for 7 days and full-mouth ultrasonic debridement will be performed to treat diseased sites.	Procedure: Full-mouth ultrasonic debridement; Full-mouth ultrasonic debridement will be performed in order to treat diseased sites; Other Names: Periodontal debridement; Drug: Clarithromycin; Administration of Clarithromycin 500mg bid for 7 days; Other Names: Biaxin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinical Attachment Level (CAL)	Evaluate the difference between baseline and 6 months CAL measures.	Baseline, 3 and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Probing Depth (PB)	Evaluate the difference between baseline and 6 months PB measures.	Baseline, 3 and 6 months
Change in Bleeding on Probe (BoP)	Evaluate the difference between baseline and 6 months BoP measures.	Baseline, 3 and 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compliance	After 7 days of periodontal treatment, patients will be asked to return any medication not taken and/or the empty bottles. The number of pills not taken by the subject will be documented in order to evaluate compliance.	One week post treatment
Adverse Effects That May be Related to Antibiotic Treatment	Patients will be instructed to fill a self-report form about any possible adverse effects in order to help evaluate their adherence to the systemic antimicrobial regimen.	One week post treatment

Collaborators and Investigators

• Sponsor: Universidade Estadual Paulista Júlio de Mesquita Filho
• Investigators: Principal Investigator: Mauro P Santamaria, PhD, Universidade Estadual Paulista Júlio de Mesquita Filho

Publications and helpful links

General Publications

• Mestnik MJ, Feres M, Figueiredo LC, Duarte PM, Lira EA, Faveri M. Short-term benefits of the adjunctive use of metronidazole plus amoxicillin in the microbial profile and in the clinical parameters of subjects with generalized aggressive periodontitis. J Clin Periodontol. 2010 Apr;37(4):353-65. doi: 10.1111/j.1600-051X.2010.01538.x.
• Khattri S, Kumbargere Nagraj S, Arora A, Eachempati P, Kusum CK, Bhat KG, Johnson TM, Lodi G. Adjunctive systemic antimicrobials for the non-surgical treatment of periodontitis. Cochrane Database Syst Rev. 2020 Nov 16;11(11):CD012568. doi: 10.1002/14651858.CD012568.pub2.
• Pradeep AR, Kathariya R. Clarithromycin, as an adjunct to non surgical periodontal therapy for chronic periodontitis: a double blinded, placebo controlled, randomized clinical trial. Arch Oral Biol. 2011 Oct;56(10):1112-9. doi: 10.1016/j.archoralbio.2011.03.021. Epub 2011 May 6.
• Araujo CF, Andere NMRB, Castro Dos Santos NC, Mathias-Santamaria IF, Reis AA, de Oliveira LD, Jardini MAN, Casarin RCV, Santamaria MP. Two different antibiotic protocols as adjuncts to one-stage full-mouth ultrasonic debridement to treat generalized aggressive periodontitis: A pilot randomized controlled clinical trial. J Periodontol. 2019 Dec;90(12):1431-1440. doi: 10.1002/JPER.18-0399. Epub 2019 Jul 16.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: November 7, 2016
• First Submitted That Met QC Criteria: November 18, 2016
• First Posted (Estimate): November 21, 2016

Study Record Updates

• Last Update Posted (Actual): December 28, 2021
• Last Update Submitted That Met QC Criteria: December 23, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Metronidazole; Clarithromycin; Amoxicillin; Full-mouth ultrasonic debridement
• Additional Relevant MeSH Terms: Behavioral Symptoms; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Aggression; Periodontitis; Aggressive Periodontitis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole; Amoxicillin; Clarithromycin
• Other Study ID Numbers: AmxMetClmCFA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No