Two Different Antibiotic Agents to Treat Generalized Aggressive Periodontitis

• Sponsor: Universidade Estadual Paulista Júlio de Mesquita Filho (Other)
• Overall Status: Completed
• CT.gov ID: NCT02969928
• Collaborator: (none)
• Enrollment: 46
• Location: 1
• Arms: 2
• Duration (Months): 21.1
• Patients Per Site Per Month: 2.2

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Aggressive Periodontitis	Procedure: Full-mouth ultrasonic debridement; Drug: Clarithromycin; Drug: Amoxicillin; Drug: Metronidazole	Phase 2/Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Full-mouth Periodontal Debridement Associated With Two Different Antibiotic Agents to Treat Generalized Aggressive Periodontitis: Randomized Controlled Clinical Trial
• Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Clinical Attachment Level (CAL) [Baseline, 3 and 6 months]

   Evaluate the difference between baseline and 6 months CAL measures.

Secondary Outcome Measures

1. Change in Probing Depth (PB) [Baseline, 3 and 6 months]

   Evaluate the difference between baseline and 6 months PB measures.

2. Change in Bleeding on Probe (BoP) [Baseline, 3 and 6 months]

   Evaluate the difference between baseline and 6 months BoP measures.

Other Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	College of Dentistry - São José dos Campos, Sao Paulo State University	São José dos Campos	SP	Brazil	12245-310

Sponsors and Collaborators

• Universidade Estadual Paulista Júlio de Mesquita Filho

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

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.
• 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.

• Responsible Party: Mauro Pedrine Santamaria, Professor, Universidade Estadual Paulista Júlio de Mesquita Filho
• ClinicalTrials.gov Identifier: NCT02969928
• Other Study ID Numbers: AmxMetClmCFA
• First Posted: Nov 21, 2016
• Last Update Posted: Dec 28, 2021
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Mauro Pedrine Santamaria, Professor, Universidade Estadual Paulista Júlio de Mesquita Filho: Full-mouth ultrasonic debridement; Clarithromycin; Amoxicillin; Metronidazole
• Additional relevant MeSH terms: Periodontitis; Aggressive Periodontitis; Aggression; Amoxicillin; Metronidazole; Clarithromycin

Study Results

Participant Flow

Arm/Group Title	Amoxicillin and Metronidazole	Clarithromycin
Arm/Group Description	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.	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
Period Title: Overall Study
STARTED	23	23
COMPLETED	23	23
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Amoxicillin and Metronidazole	Clarithromycin	Total
Arm/Group Description	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.	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	Total of all reporting groups
Overall Participants	23	23	46
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	23 100%	23 100%	46 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	16 69.6%	19 82.6%	35 76.1%
Male	7 30.4%	4 17.4%	11 23.9%
Region of Enrollment (participants) [Number]
Brazil	23 100%	23 100%	46 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amoxicillin and Metronidazole	Clarithromycin
Arm/Group Description	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.	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
Measure Participants	23	23
Baseline	3.69 (0.7)	3.62 (0.4)
3 months	2.4 (0.5)	3 (0.4)
6 months	3 (0.5)	3 (0.4)

2. Secondary Outcome

Title	Change in Probing Depth (PB)
Description	Evaluate the difference between baseline and 6 months PB measures.
Time Frame	Baseline, 3 and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amoxicillin and Metronidazole	Clarithromycin
Arm/Group Description	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.	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
Measure Participants	23	23
Baseline	3.44 (0.6)	3.41 (0.4)
3 months	2.5 (0.3)	2.7 (0.2)
6 months	2.6 (0.3)	2.7 (0.25)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amoxicillin and Metronidazole	Clarithromycin
Arm/Group Description	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.	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
Measure Participants	23	23
Baseline	53.4 (17.4)	43.7 (8.3)
3 months	30.2 (9.3)	24.8 (9.8)
6 months	27.3 (8.3)	23.3 (9.3)

4. Other Pre-specified Outcome

Title	Compliance
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amoxicillin and Metronidazole	Clarithromycin
Arm/Group Description	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.	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
Measure Participants	23	23
# of patients that did not take ≥1 pills	3 13%	4 17.4%
# of patients that interrupted the drug intake	2 8.7%	0 0%

5. Other Pre-specified Outcome

Title	Adverse Effects That May be Related to Antibiotic Treatment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amoxicillin and Metronidazole	Clarithromycin
Arm/Group Description	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.	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
Measure Participants	23	23
Headache	1 4.3%	2 8.7%
Stomach pain	4 17.4%	3 13%
Nausea/vomiting	3 13%	6 26.1%
Metallic taste	7 30.4%	13 56.5%
Diarrhea/abdominal pain	3 13%	3 13%
Drowsiness	2 8.7%	3 13%
Itching	1 4.3%	0 0%
Skin wounds	0 0%	0 0%
None	5 21.7%	5 21.7%

Adverse Events

Time Frame	during 7 days post-treatment
Adverse Event Reporting Description	7 days after the therapy patients returned to fill out a self-report form about 8 possible adverse effects resulting from the antibiotic intake, based on Martys: Headache, Stomach pain, Nausea/vomiting, Metallic taste, Diarrhea/ abdominal pain, Drowsiness, Itching and Skin wounds.
Arm/Group Title	Amoxicillin and Metronidazole		Clarithromycin
Arm/Group Description	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.		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
All Cause Mortality
	Amoxicillin and Metronidazole		Clarithromycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)
Serious Adverse Events
	Amoxicillin and Metronidazole		Clarithromycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Amoxicillin and Metronidazole		Clarithromycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/23 (78.3%)		18/23 (78.3%)
Gastrointestinal disorders
Stomach pain	4/23 (17.4%)		3/23 (13%)
Diarrhea/ abdominal pain	3/23 (13%)		3/23 (13%)
General disorders
Headache	1/23 (4.3%)		2/23 (8.7%)
Nausea/vomiting	3/23 (13%)		6/23 (26.1%)
Metallic taste	7/23 (30.4%)		13/23 (56.5%)
Drowsiness	2/23 (8.7%)		3/23 (13%)
Skin and subcutaneous tissue disorders
Itching	1/23 (4.3%)		0/23 (0%)
Skin wounds	0/23 (0%)		0/23 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.