Metronidazole vs Azithromycin in Periodontal Surgery for Patients Positive to Porphyromonas Gingivalis

Clinical and Microbiological Comparison of Two Different Systemic Antimicrobials (Azithromycin Versus Metronidazole) as Adjuncts to Periodontal Surgery in the Treatment of P.Gingivalis Periodontitis Patients

The objective of this study is to determine whether, in patients with non treated periodontitis (stage III and IV) positive to Porphyromonas gingivalis, the use of systemic antimicrobials (metronidazole versus azithromycin) as an adjunctive treatment to periodontal surgery provides clinical and microbiological benefits.

Study Overview

• Status: Unknown
• Conditions: Periodontitis; Surgery
• Intervention / Treatment: Other: Azithromycin; Other: Metronidazole

Detailed Description

Design: randomized, parallel and triple blind clinical trial

Sample: Patients with periodontitis (stages III and IV) and positive to Porphyromonas gingivalis who potentially need periodontal surgery were recruited. 25 patients were randomized to the test group (periodontal surgery + azithromycin) and another 25 subjects to the control group (periodontal surgery + metronidazole).

Study visits:

• Examiner calibration
• Recruitment of patients. Screening. Data collection (clinical and microbiological variables).

• Phase I.

  • Non-surgical periodontal treatment (2 visits).
  • Reevaluation at 6 weeks. Data collection (clinical and microbiological variables). Identification of study candidate patients (Patients with probing pocket depth > 5 mm and positive to Porphyromonas gingivalis). Randomization of study groups.

• Phase II. Surgical periodontal treatment.

  • Periodontal surgery sessions. In the last surgery, the antibiotic test (azithromycin) or metronidazole (control) is administered according to randomization.
  • Suture removal 1 week after performing periodontal surgery. Data collection 1 week after antibiotic consumption with the last surgery (patient-centered variables on the side effects of antibiotics).
  • Re-evaluation of the surgical phase at 6 weeks after the last surgery session. Data collection (clinical variables).

• Phase III. Periodontal maintenance.

  • Maintenance 1 (3 months post surgery). Data collection (Clinical and microbiological variables).
  • Maintenance 2 (6 months post surgery). Data collection (Clinical and microbiological variables).
  • Maintenance 3 (9 months post surgery). Data collection (Clinical variables).
  • Maintenance 4 (12 months post surgery). Data collection (Clinical and microbiological variables).
  • Maintenance 5 (4 years post surgery). Data collection (Clinical and microbiological variables).

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28040
    • Faculty of Dentistry, Univesity Complutense, Madrid

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of periodontitis (stages III or IV) that may require periodontal surgery
• Have at least 10 teeth in function, excluding third molars.
• Present locations with probing depth (PS)> 6 mm in at least 30% of the teeth.
• Present radiographic evidence of moderate-severe bone loss in at least 30% of the dentition.
• Detection of P. gingivalis in subgingival samples taken at the screening visit as well as in the post-scaling and root planning visit and processed by culture.
• Systemically healthy patients.

Exclusion Criteria:

• Pregnant or lactating women.
• Presenting systemic pathology and / or taking medication that may affect the periodontal situation and / or patients requiring antibiotic prophylaxis.
• Have received systemic antimicrobial treatment in the previous 6 months.
• Have received periodontal treatment in the 6 months prior to the beginning of the study.
• Patients allergic to metronidazole, or to any of the components of commercial formulations thereof (Flagyl®).
• Patients allergic to azithromycin, or to any of the components of commercial formulations thereof (Zithromax®).
• Patients who refuse to sign the informed consent.

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
Experimental: azythromycin + periodontal surgery.; Periodontal surgery + Azithromycin (500 mg every 24 h for 3 days).	Other: Azithromycin; azithromycin (500 mg/24h/3 days)
Active Comparator: metronidazole + periodontal surgery; Periodontal surgery + Metronidazole (500 mg every 8 h for 7 days).	Other: Metronidazole; metronidazole (500 mg/8h/7 days)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probing pocket depth (PPD)	Full mouth measurement at 6 sites per tooth, with a manual periodontal probe University North Carolina 15 (UNC-15 mm)	At 6 weeks after periodontal surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probing pocket depth (PPD)	Full mouth measurement at 6 sites per tooth, with a manual periodontal probe UNC-15 mm	At the beginning of the study, 6 weeks after scaling and root planning (Reevaluation phase I), 6 weeks after the last surgery session (Reevaluation Phase II) and during the maintenance Phase III (3, 6, 9, 12 and 48 months after periodontal surgery)
Gingival Recession (REC)	Full mouth measurement at 6 sites per tooth, with a manual periodontal probe UNC-15 mm	At the beginning of the study, 6 weeks after scaling and root planning (Reevaluation phase I), 6 weeks after the last surgery session (Reevaluation Phase II) and during the maintenance Phase III (3, 6, 9, 12 and 48 months after periodontal surgery)
Plaque index (PlI)	Full mouth measurement at 6 sites per tooth, with a manual periodontal probe UNC-15 mm	At the beginning of the study, 6 weeks after scaling and root planning (Reevaluation phase I), 6 weeks after the last surgery session (Reevaluation Phase II) and during the maintenance Phase III (3, 6, 9, 12 and 48 months after periodontal surgery)
Gingival index (GI)	Full mouth measurement of the bleeding on probing at 6 sites per tooth, with a manual periodontal probe UNC-15 mm	At the beginning of the study, 6 weeks after scaling and root planning (Reevaluation phase I), 6 weeks after the last surgery session (Reevaluation Phase II) and during the maintenance Phase III (3, 6, 9, 12 and 48 months after periodontal surgery)
Furcations	Measurement of furcations with a manual periodontal probe UNC-15 mm	At the beginning of the study, 6 weeks after scaling and root planning (Reevaluation phase I), 6 weeks after the last surgery session (Reevaluation Phase II) and during the maintenance Phase III (3, 6, 9, 12 and 48 months after periodontal surgery)
Clinical attachment level (CAL)	Full mouth measurement at 6 sites per tooth, with a manual periodontal probe UNC-15 mm	At the beginning of the study, 6 weeks after scaling and root planning (Reevaluation phase I), 6 weeks after the last surgery session (Reevaluation Phase II) and during the maintenance Phase III (3, 6, 9, 12 and 48 months after periodontal surgery)
Total bacterial counts	A microbiological sample is taken with sterilized paper points from the gingival crevicular fluid and the total bacterial counts (expressed in total colony-forming units) are analyzed by culture.	At the beginning of the study, 6 weeks after scaling and root planning (Reevaluation phase I) and during the maintenance Phase III (3, 6, 12 and 48 months after periodontal surgery)
Percentage of periodontal pathogens	Determination of the percentage of the following periodontal pathogens: Porphyromonas gingivalis; Tannerella forsythia; Aggregatibacter actinomycetemcomitans; Prevotella intermedia; Fusobacterium nucleatum; Eikenella corrodens; Campylobacter rectus; Capnocytophaga sp.; Enterobacter sp.	At the beginning of the study, 6 weeks after scaling and root planning (Reevaluation phase I) and during the maintenance Phase III (3, 6, 12 and 48 months after periodontal surgery)
Counts of periodontal pathogens	Determination of the following periodontal pathogens: Porphyromonas gingivalis; Tannerella forsythia; Aggregatibacter actinomycetemcomitans; Prevotella intermedia; Fusobacterium nucleatum; Eikenella corrodens; Campylobacter rectus; Capnocytophaga sp.; Enterobacter sp.	At the beginning of the study, 6 weeks after scaling and root planning (Reevaluation phase I) and during the maintenance Phase III (3, 6, 12 and 48 months after periodontal surgery)
Appearance of side effects after taking antibiotic	The patient was asked if he had side effects after taking antibiotic (Yes / No)	1 week after antibiotic consumption
Type of adverse effect after taking antibiotic	The patient was asked to write freely on a form the type of side effect suffered	1 week after antibiotic consumption
Degree of affectation	The patient was asked to categorize the degree of affectation (mild, moderate or severe) of the secondary effect of the antibiotic if it had appeared.	1 week after antibiotic consumption

Collaborators and Investigators

• Sponsor: Universidad Complutense de Madrid
• Investigators: Study Director: Mariano Sanz, University Complutense Madrid (UCM)

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Anticipated): July 1, 2019
• Study Completion (Anticipated): July 1, 2019

Study Registration Dates

• First Submitted: February 20, 2019
• First Submitted That Met QC Criteria: March 1, 2019
• First Posted (Actual): March 5, 2019

Study Record Updates

• Last Update Posted (Actual): March 5, 2019
• Last Update Submitted That Met QC Criteria: March 1, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Metronidazole; Microbiota; Disease Progression; Azithromycin; Porphyromonas gingivalis; Periodontitis/surgery; Periodontitis/therapy; Periodontitis/drug effect; Periodontitis/drug therapy; Periodontal diseases/surgery; Periodontal diseases/therapy; Periodontal pocket/drug therapy; Metronidazole/therapeutic use; Periodontal pocket/surgery; Periodontal pocket/therapy; Azithromycin/therapeutic use
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Periodontitis; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole; Azithromycin
• Other Study ID Numbers: ATB1

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No