Periodontal Debridement Associated With Systemic Antibiotics and Single/Repeated PDT to Treat Aggressive Periodontitis

NCT ID: NCT03132714

Last Updated: 2017-04-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

46 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-03-31

Study Completion Date

2016-10-31

Brief Summary

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The aim of this project is to compare the efficacy and the local effect of the association of single or repeated application of photodynamic therapy (PDT) with antibiotic agents using Amoxicillin + Metronidazole or Clarithromycin in the treatment of patients with Generalized Aggressive Periodontitis (GAgP).

Detailed Description

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The study methodology is according to CONSORT-STATEMENT 2010 and SPIRIT 2013 for randomized controlled clinical trials.

Study Design

The study is designed as a prospective, interventional, parallel, blinded, randomized, controlled clinical trial aimed to compare the efficacy and the local effect of the association of single or repeated application of photodynamic therapy (PDT) with antibiotic agents using Amoxicillin + Metronidazole or Clarithromycin in the treatment of patients with Generalized Aggressive Periodontitis (GAgP).

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. Each one of 46 patients will have three pockets with probing depth and loss of clinical attachment level ≥5 mm and bleeding on probing not located at furcation sites randomly chosen.

Power calculation

A population of 46 patients (138 periodontal pockets, 3 per patient) that meet the pre-established criteria will be considered. Considering α = 5% and a β = 5% to detect a difference of 1 mm between groups in probing depth reduction of pockets ≥5 mm, for a standard deviation of 0.8 mm, 14 patients will be needed in each group. With a sample of 46 patients (138 pockets), the study will have a power greater than 95%.

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 antibiotic groups (that will receive Amoxicillin + Metronidazole or Clarithromycin) 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 compounding pharmacy. The same person outside the project will generate a random sequence regarding the type of PDT application for each patient, for the three previously selected pockets (single or repeated application of PDT or control), which will be revealed shortly after the periodontal debridement session.

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 (NA), different from the examiner (ca). Immediately before the mechanical therapy, patients will be allocated in one of the two treatment protocols: Clarithromycin (CLM) group (n = 22): FMUD + CLM 500 mg bid, for 7 days or 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 the FMUD session.

After periodontal debridement (PD), two periodontal pockets from each patient will receive the proposed PDT protocols to assist the decontamination of diseased sites. One pocket will receive a single application of PDT (sPDT) (baseline only) and the other will receive repeated application of PDT (rPDT). After subgingival irrigation with saline solution to wash the pocket, the photosensitizer (methylene blue 10 mg / mL) will be applied to the bottom of the pocket by buccal side until it is completely filled. After one minute, the pocket will be washed with water and exposed to low-level laser (TheraLase - Brazil), with a corresponding optical fiber of 600 um diameter, which will be inserted into the pocket. A 660 nm wavelength with a power of 60 milliwatts and a dose of 129 J / cm2 will be used for one minute. The same procedure will be repeated by lingual site, totaling two minutes of application per pocket. The repeated application protocol will consist of 5 applications on different days, performed on the day of periodontal treatment (baseline - 0), 1, 2, 7 and 14 days after. Thus, the following comparative groups will be formed, totaling 138 pockets:

PD + (AMX + MET) (n = 23): periodontal pockets that will receive periodontal debridement associated with Amoxicillin + Metronidazole;

PD + CLM (n = 23): periodontal pockets that will receive periodontal debridement associated with the use of Clarithromycin;

PD + (AMX + MET) + sPDT (n = 23): periodontal pockets that will receive periodontal debridement associated with Amoxicillin + Metronidazole and single application of PDT; PD + CLM + sPDT (n = 23): periodontal pockets that will receive periodontal debridement associated with the use of Clarithromycin and single application of PDT;

PD + (AMX + MET) + rPDT (n = 23) : periodontal pockets that will receive periodontal debridement associated with Amoxicillin + Metronidazole and repeated application of PDT;

PD + CLM + rPDT (n = 23): periodontal pockets that will receive periodontal debridement associated with Clarithromycin and repeated application of PDT

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.

Conditions

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Aggressive Periodontitis, Generalized

Keywords

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Full-mouth ultrasonic debridement Clarithromycin Amoxicillin Metronidazole Antimicrobial therapy Photodynamic therapy Low-level laser therapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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PD + (AMX + MET)

periodontal pockets that will receive full-mouth ultrasonic debridement associated with systemic Amoxicillin 500 mg + Metronidazole 400 mg

Group Type ACTIVE_COMPARATOR

Full-mouth ultrasonic debridement

Intervention Type PROCEDURE

Full-mouth ultrasonic debridement will be performed in order to treat diseased sites

Amoxicillin 500mg

Intervention Type DRUG

Administration of Amoxicillin 500mg tid for 7 days

Metronidazole 400mg

Intervention Type DRUG

Administration of Metronidazole 400mg tid for 7 days.

PD + CLM

periodontal pockets that will receive full-mouth ultrasonic debridement associated with systemic clarithromycin 500 mg

Group Type ACTIVE_COMPARATOR

Full-mouth ultrasonic debridement

Intervention Type PROCEDURE

Full-mouth ultrasonic debridement will be performed in order to treat diseased sites

Clarithromycin 500mg

Intervention Type DRUG

Administration of Clarithromycin 500mg bid for 7 days

PD + (AMX + MET) + sPDT

periodontal pockets that will receive full-mouth ultrasonic debridement associated with systemic Amoxicillin 500 mg + Metronidazole 400 mg and single application of PDT

Group Type ACTIVE_COMPARATOR

Full-mouth ultrasonic debridement

Intervention Type PROCEDURE

Full-mouth ultrasonic debridement will be performed in order to treat diseased sites

Amoxicillin 500mg

Intervention Type DRUG

Administration of Amoxicillin 500mg tid for 7 days

Metronidazole 400mg

Intervention Type DRUG

Administration of Metronidazole 400mg tid for 7 days.

Single application of PDT

Intervention Type PROCEDURE

Single application of photodynamic therapy (PDT) at day 0.

PD + CLM + sPDT

periodontal pockets that will receive full-mouth ultrasonic debridement associated with systemic Clarithromycin 500 mg and single application of PDT

Group Type ACTIVE_COMPARATOR

Full-mouth ultrasonic debridement

Intervention Type PROCEDURE

Full-mouth ultrasonic debridement will be performed in order to treat diseased sites

Clarithromycin 500mg

Intervention Type DRUG

Administration of Clarithromycin 500mg bid for 7 days

Single application of PDT

Intervention Type PROCEDURE

Single application of photodynamic therapy (PDT) at day 0.

PD + (AMX + MET) + rPDT

periodontal pockets that will receive full-mouth ultrasonic debridement associated with systemic Amoxicillin 500 mg + Metronidazole 400 mg and repeated application of PDT

Group Type ACTIVE_COMPARATOR

Full-mouth ultrasonic debridement

Intervention Type PROCEDURE

Full-mouth ultrasonic debridement will be performed in order to treat diseased sites

Amoxicillin 500mg

Intervention Type DRUG

Administration of Amoxicillin 500mg tid for 7 days

Metronidazole 400mg

Intervention Type DRUG

Administration of Metronidazole 400mg tid for 7 days.

Repeated application of PDT

Intervention Type PROCEDURE

Repeated application of photodynamic therapy (PDT) at 0, 1, 2, 7 and 14 days post-operatively.

PD + CLM + rPDT

periodontal pockets that will receive full-mouth ultrasonic debridement associated with systemic Clarithromycin 500 mg and repeated application of PDT

Group Type ACTIVE_COMPARATOR

Full-mouth ultrasonic debridement

Intervention Type PROCEDURE

Full-mouth ultrasonic debridement will be performed in order to treat diseased sites

Clarithromycin 500mg

Intervention Type DRUG

Administration of Clarithromycin 500mg bid for 7 days

Repeated application of PDT

Intervention Type PROCEDURE

Repeated application of photodynamic therapy (PDT) at 0, 1, 2, 7 and 14 days post-operatively.

Interventions

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Full-mouth ultrasonic debridement

Full-mouth ultrasonic debridement will be performed in order to treat diseased sites

Intervention Type PROCEDURE

Amoxicillin 500mg

Administration of Amoxicillin 500mg tid for 7 days

Intervention Type DRUG

Metronidazole 400mg

Administration of Metronidazole 400mg tid for 7 days.

Intervention Type DRUG

Clarithromycin 500mg

Administration of Clarithromycin 500mg bid for 7 days

Intervention Type DRUG

Single application of PDT

Single application of photodynamic therapy (PDT) at day 0.

Intervention Type PROCEDURE

Repeated application of PDT

Repeated application of photodynamic therapy (PDT) at 0, 1, 2, 7 and 14 days post-operatively.

Intervention Type PROCEDURE

Other Intervention Names

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Periodontal debridement Amoxil Flagyl Biaxin

Eligibility Criteria

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Inclusion Criteria

* diagnosis of GAgP (Armitage, 1999; American Academy of Periodontology, 2015);
* presence of ≥20 teeth, excluding third molars and teeth indicated for extraction;
* presence of ≥6 sites presenting PD ≥5 mm with bleeding on probing and ≥2 sites with PD ≥7 mm (including incisors and first molars, in addition to two other non-contiguous teeth between them);
* presence of three non-adjacent periodontal pockets with probing depth ≥5 mm and bleeding on probing not located in furcation area;
* good general health (ASA I/II);
* 18-35 years old;
* agree to participate in the study and sign a written consent (Resolution # 196 of October 1996 and the Brazilian Professional Code of Dental Ethics - 179/93).

Exclusion Criteria

* pregnant or nursing;
* suffer from any systemic disease (e.g. cardiovascular, diabetes, blood dyscrasias, immunodeficiency, etc - ASA III/IV/V);
* antimicrobials or anti-inflammatory drugs in the previous 6 months;
* periodontal treatment within the last 12 months;
* smoke ≥10 cigarettes/day;
* reported allergy to amoxicillin, metronidazole or clarithromycin;
* required antibiotic prophylaxis;
* current use of any medication that could interfere with periodontal response were excluded from the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Universidade Estadual Paulista Júlio de Mesquita Filho

OTHER

Sponsor Role lead

Responsible Party

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Mauro Pedrine Santamaria

PhD Adjunct professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Mauro P Santamaria, DDS, PhD

Role: PRINCIPAL_INVESTIGATOR

Universidade Estadual Paulista Júlio de Mesquita Filho

Locations

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College of Dentistry - São José dos Campos, São Paulo State University

São José dos Campos, São Paulo, Brazil

Site Status

Countries

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Brazil

References

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Lulic M, Leiggener Gorog I, Salvi GE, Ramseier CA, Mattheos N, Lang NP. One-year outcomes of repeated adjunctive photodynamic therapy during periodontal maintenance: a proof-of-principle randomized-controlled clinical trial. J Clin Periodontol. 2009 Aug;36(8):661-6. doi: 10.1111/j.1600-051X.2009.01432.x. Epub 2009 Jun 25.

Reference Type BACKGROUND
PMID: 19563331 (View on PubMed)

Other Identifiers

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rPDT&antibioticsCFA

Identifier Type: -

Identifier Source: org_study_id