Two Different Antibiotic Agents to Treat Generalized Aggressive Periodontitis

Phase 2

Completed

Conditions: Aggressive Periodontitis

Interventions: Procedure: Full-mouth ultrasonic debridement
Drug: Amoxicillin
Drug: Clarithromycin
Drug: Metronidazole

Registration Number: NCT02969928

Lead Sponsor: Universidade Estadual Paulista Júlio de Mesquita Filho

Brief Summary: 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).

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 46

Inclusion Criteria

diagnosis of GAgP (AAP, 1999);
presence of ≥20 teeth;
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);
good general health;
≤ 35 years old; and
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

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Amoxicillin and Metronidazole	Amoxicillin	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.
Amoxicillin and Metronidazole	Full-mouth ultrasonic debridement	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.
Clarithromycin	Full-mouth ultrasonic debridement	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.
Amoxicillin and Metronidazole	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.
Clarithromycin	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.

Primary Outcome Measures

Name	Time	Method
Change in Clinical Attachment Level (CAL)	Baseline, 3 and 6 months	Evaluate the difference between baseline and 6 months CAL measures.

Secondary Outcome Measures

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