Aggressive Periodontitis
Conditions
Keywords
Full-mouth ultrasonic debridement, Clarithromycin, Amoxicillin, Metronidazole
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.
Interventions
PROCEDUREFull-mouth ultrasonic debridement
Full-mouth ultrasonic debridement will be performed in order to treat diseased sites
DRUGClarithromycin
Administration of Clarithromycin 500mg bid for 7 days
DRUGAmoxicillin
Administration of Amoxicillin 500mg tid for 7 days.
DRUGMetronidazole
Administration of Metronidazole 400mg tid for 7 days.
Sponsors
Universidade Estadual Paulista Júlio de Mesquita Filho
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinical Attachment Level (CAL) | Baseline, 3 and 6 months | Evaluate the difference between baseline and 6 months CAL measures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Compliance | One week post treatment | 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. |
| Adverse Effects That May be Related to Antibiotic Treatment | One week post 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. |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Full-mouth ultrasonic debridement: Full-mouth ultrasonic debridement will be performed in order to treat diseased sites
Amoxicillin: Administration of Amoxicillin 500mg tid for 7 days.
Metronidazole: Administration of Metronidazole 400mg tid for 7 days. | 23 |
| 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.
Full-mouth ultrasonic debridement: Full-mouth ultrasonic debridement will be performed in order to treat diseased sites
Clarithromycin: Administration of Clarithromycin 500mg bid for 7 days | 23 |
| Total | 46 |
Baseline characteristics
| Characteristic | Amoxicillin and Metronidazole | Clarithromycin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 23 Participants | 46 Participants |
| Region of Enrollment Brazil | 23 participants | 23 participants | 46 participants |
| Sex: Female, Male Female | 16 Participants | 19 Participants | 35 Participants |
| Sex: Female, Male Male | 7 Participants | 4 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 18 / 23 | 18 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
Change in Clinical Attachment Level (CAL)
Evaluate the difference between baseline and 6 months CAL measures.
Time frame: Baseline, 3 and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin and Metronidazole | Change in Clinical Attachment Level (CAL) | Baseline | 3.69 mm | Standard Deviation 0.7 |
| Amoxicillin and Metronidazole | Change in Clinical Attachment Level (CAL) | 3 months | 2.4 mm | Standard Deviation 0.5 |
| Amoxicillin and Metronidazole | Change in Clinical Attachment Level (CAL) | 6 months | 3 mm | Standard Deviation 0.5 |
| Clarithromycin | Change in Clinical Attachment Level (CAL) | Baseline | 3.62 mm | Standard Deviation 0.4 |
| Clarithromycin | Change in Clinical Attachment Level (CAL) | 3 months | 3 mm | Standard Deviation 0.4 |
| Clarithromycin | Change in Clinical Attachment Level (CAL) | 6 months | 3 mm | Standard Deviation 0.4 |
Secondary
Change in Bleeding on Probe (BoP)
Evaluate the difference between baseline and 6 months BoP measures.
Time frame: Baseline, 3 and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin and Metronidazole | Change in Bleeding on Probe (BoP) | Baseline | 53.4 % of sites with bleeding on probe | Standard Deviation 17.4 |
| Amoxicillin and Metronidazole | Change in Bleeding on Probe (BoP) | 3 months | 30.2 % of sites with bleeding on probe | Standard Deviation 9.3 |
| Amoxicillin and Metronidazole | Change in Bleeding on Probe (BoP) | 6 months | 27.3 % of sites with bleeding on probe | Standard Deviation 8.3 |
| Clarithromycin | Change in Bleeding on Probe (BoP) | Baseline | 43.7 % of sites with bleeding on probe | Standard Deviation 8.3 |
| Clarithromycin | Change in Bleeding on Probe (BoP) | 3 months | 24.8 % of sites with bleeding on probe | Standard Deviation 9.8 |
| Clarithromycin | Change in Bleeding on Probe (BoP) | 6 months | 23.3 % of sites with bleeding on probe | Standard Deviation 9.3 |
Secondary
Change in Probing Depth (PB)
Evaluate the difference between baseline and 6 months PB measures.
Time frame: Baseline, 3 and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin and Metronidazole | Change in Probing Depth (PB) | Baseline | 3.44 mm | Standard Deviation 0.6 |
| Amoxicillin and Metronidazole | Change in Probing Depth (PB) | 3 months | 2.5 mm | Standard Deviation 0.3 |
| Amoxicillin and Metronidazole | Change in Probing Depth (PB) | 6 months | 2.6 mm | Standard Deviation 0.3 |
| Clarithromycin | Change in Probing Depth (PB) | Baseline | 3.41 mm | Standard Deviation 0.4 |
| Clarithromycin | Change in Probing Depth (PB) | 3 months | 2.7 mm | Standard Deviation 0.2 |
| Clarithromycin | Change in Probing Depth (PB) | 6 months | 2.7 mm | Standard Deviation 0.25 |
Other Pre-specified
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.
Time frame: One week post treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin and Metronidazole | Adverse Effects That May be Related to Antibiotic Treatment | Stomach pain | 4 Participants |
| Amoxicillin and Metronidazole | Adverse Effects That May be Related to Antibiotic Treatment | Drowsiness | 2 Participants |
| Amoxicillin and Metronidazole | Adverse Effects That May be Related to Antibiotic Treatment | Metallic taste | 7 Participants |
| Amoxicillin and Metronidazole | Adverse Effects That May be Related to Antibiotic Treatment | Itching | 1 Participants |
| Amoxicillin and Metronidazole | Adverse Effects That May be Related to Antibiotic Treatment | Nausea/vomiting | 3 Participants |
| Amoxicillin and Metronidazole | Adverse Effects That May be Related to Antibiotic Treatment | Skin wounds | 0 Participants |
| Amoxicillin and Metronidazole | Adverse Effects That May be Related to Antibiotic Treatment | Diarrhea/abdominal pain | 3 Participants |
| Amoxicillin and Metronidazole | Adverse Effects That May be Related to Antibiotic Treatment | None | 5 Participants |
| Amoxicillin and Metronidazole | Adverse Effects That May be Related to Antibiotic Treatment | Headache | 1 Participants |
| Clarithromycin | Adverse Effects That May be Related to Antibiotic Treatment | None | 5 Participants |
| Clarithromycin | Adverse Effects That May be Related to Antibiotic Treatment | Headache | 2 Participants |
| Clarithromycin | Adverse Effects That May be Related to Antibiotic Treatment | Stomach pain | 3 Participants |
| Clarithromycin | Adverse Effects That May be Related to Antibiotic Treatment | Nausea/vomiting | 6 Participants |
| Clarithromycin | Adverse Effects That May be Related to Antibiotic Treatment | Metallic taste | 13 Participants |
| Clarithromycin | Adverse Effects That May be Related to Antibiotic Treatment | Diarrhea/abdominal pain | 3 Participants |
| Clarithromycin | Adverse Effects That May be Related to Antibiotic Treatment | Drowsiness | 3 Participants |
| Clarithromycin | Adverse Effects That May be Related to Antibiotic Treatment | Itching | 0 Participants |
| Clarithromycin | Adverse Effects That May be Related to Antibiotic Treatment | Skin wounds | 0 Participants |
Other Pre-specified
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.
Time frame: One week post treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin and Metronidazole | Compliance | # of patients that did not take ≥1 pills | 3 Participants |
| Amoxicillin and Metronidazole | Compliance | # of patients that interrupted the drug intake | 2 Participants |
| Clarithromycin | Compliance | # of patients that did not take ≥1 pills | 4 Participants |
| Clarithromycin | Compliance | # of patients that interrupted the drug intake | 0 Participants |