Antibiotics as Adjuncts to Periodontal Therapy:Pharmacokinetic Considerations and Dosing Strategies

NCT04669717 | Recruiting Phase 4 DMC

• 1 other identifier: BASEC 2020-01074
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Periodontitits is a bacteria induced inflammatory disease that destroys the supporting tissues of the tooth and leads to tooth loss. Treatment consists mainly of the mechanical cleaning of the tooth surfaces in order to remove the bacterial deposits (plaque and calculus). This procedure can reduce the level of pathogenic bacteria but it can not eradicate them. In severe cases, for the complete resolution of the disease, the elimantion of certain species of bacteria is needed. In order to achieve that, the combination of different regimens of antibiotics adjunctive to the mechanical treatment has been proposed. However, dosage and duration of antimicrobial therapy should be optimal and not excessive as issues may arise related to increased antimicrobial resistance in the population and the individual due to habitual prescription of wide-spectrum antibiotic regimens, horizontal gene transfer and genetic mutation. In the present study, in an effort to optimize the dosage and duration of the antimicrobial regimen, we will determine the pharmacokinetics (PK) and pharmacodynamic (PD) properties of the MET-AMO combination and of AZI in Gingival Crevicular Fluid (GCF), saliva and serum in severe periodontitis patients during and after either a 3-day or a 7-day course of treatment.

Conditions

Periodontal Diseases; Antibiotics; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• The concentration of AMO+MET and AZI in GCF, saliva and serum

  The concentration of the drugs will be assessed in samples of gingival crevicular fluid, saliva and serum at days 0, 2, 4 and 8 after the start of the antibiotic administration.The concentration of the studied antibiotics in the different fluids will be expressed as ng/ml

  At Day 0,2,4,8 post-dose

Secondary Outcomes (4)

• Differences between the three treatment arms in the proportion of participants classed as treatment success at 6 months; defined as absence of sites with PD ≥ 5 mm and concomitant bleeding on probing.

  At Month 3 and Month 6 post-intervention

• Differences between the three treatment arms in the levels of 6 organisms in subgingival plaque samples. For those bacteria with a threshold of >1000cells/ml, results will be expressed as median counts.

  At Month 3 and Month 6 post-intervention

• Number of participant per treatment arm with adverse events as a mesure of safety.

  At Day 2, Day 4 and Day 8 post-intervention

• Patient's compliance will be evaluated

  At Day 8 after intervention

Study Arms (3)

Amoxicilline and Metronidazole for 7 days

ACTIVE COMPARATOR

Drug: AMOXICILLINE Sandoz cpr pell 500mg, Sandoz Pharmaceuticals AG + FLAGYL cpr pell 500mg, Sanofi-Aventis ( Suisse) SA, 3/d for 7 days Systemic antibiotics after sub gingival mechanical debridement

Drug: 3/d 500 mg Amoxicilline Sandoz plus 500 mg Flagyl for 7 days

Amoxicilline and Metronidazole for 3 days

ACTIVE COMPARATOR

Drug: AMOXICILLINE Sandoz cpr pell 500mg, Sandoz Pharmaceuticals AG + FLAGYL cpr pell 500mg, Sanofi-Aventis ( Suisse) SA, 3/d for 3 days Systemic antibiotics after sub gingival mechanical debridement

Drug: 3/d 500 mg Amoxicilline Sandoz plus 500 mg Flagyl for 3 days

Azithromycine for 3 days

ACTIVE COMPARATOR

Drug: AZITHROMYCIN Pfizer cpr pell 500mg, Pfizer PFE Switzerland GmbH 1/d 500mg for 3 days Systemic antibiotics after sub gingival mechanical debridement

Drug: 1/d 500 mg Azithromycine Pfizer for 3 days

Interventions

3/d 500 mg Amoxicilline Sandoz plus 500 mg Flagyl for 7 days DRUG

Non-surgical periodontal therapy and radnomly administration of the antibiotics

Also known as: AMOXICILLINE Sandoz cpr pell 500 mg, Sandoz Pharmaceuticals AG + FLAGYL cpr pell 500 mg, Sanofi-Aventis ( Suisse) SA

Amoxicilline and Metronidazole for 7 days

3/d 500 mg Amoxicilline Sandoz plus 500 mg Flagyl for 3 days DRUG

Non-surgical periodontal therapy and radnomly administration of the antibiotics

Also known as: AMOXICILLINE Sandoz cpr pell 500 mg, Sandoz Pharmaceuticals AG + FLAGYL cpr pell 500 mg, Sanofi-Aventis ( Suisse) SA

Amoxicilline and Metronidazole for 3 days

1/d 500 mg Azithromycine Pfizer for 3 days DRUG

Non-surgical periodontal therapy and radnomly administration of the antibiotics

Also known as: AZITHROMYCIN Pfizer cpr pell 500mg, Pfizer PFE Switzerland GmbH

Azithromycine for 3 days

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed Consent as documented by signature
• Aged 18-80 years old with need of periodontal treatment associated with adjunctive antibiotic therapy
• Presence of at least 30% of the teeth in the mouth with PD\>6mm and BOP

You may not qualify if:

• Persons with systemic illnesses (uncontrolled diabetes mellitus, cancer, human immunodeficiency virus, bone metabolic diseases or disorders that compromise wound healing, radiation, or immunosuppressive therapy)
• Pregnancy or lactation
• Persons who had taken AB within the previous 2 months
• Persons who are taking nonsteroidal anti-inflammatory drugs
• Persons who have a confirmed or suspected intolerance to 5-nitroimidazole derivatives or amoxicillin or macrolides
• Previous periodontal therapy the last 1 year
• Known or suspected non-compliance, drug or alcohol abuse
• Inability to follow due to language problems, psychological disorders, dementia, etc. of the participant
• Participants not willing to attend regular dental maintenance visits and follow-up evaluations
• Participation in another study with investigational drug within the 30 days preceding and during the present study

Sponsors & Collaborators

• University of Geneva, Switzerland: lead
• University of Lausanne: collaborator

Study Sites (1)

University of Geneva, University Clinics of Dental Medicine

Geneva, Canton of Geneva, 1205, Switzerland

RECRUITING

Related Publications (1)

• Giannopoulou C, Cionca N, Almaghlouth A, Cancela J, Courvoisier DS, Mombelli A. Systemic Biomarkers in 2-Phase Antibiotic Periodontal Treatment: A Randomized Clinical Trial. J Dent Res. 2016 Mar;95(3):349-55. doi: 10.1177/0022034515618949. Epub 2015 Nov 24.

  PMID: 26604272 BACKGROUND

MeSH Terms

Conditions

Periodontal Diseases

Interventions

Metronidazole

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Catherine Giannopoulou, Dr med dent

  University Clinics of Dental Medicine, University of Geneva

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Catherine Giannopoulou, Dr med dent

CONTACT

0041223794068; ekaterini.giannopoulou@unige.ch

Alkisti Zekeridou, Dr med dent

CONTACT

0041223794031; alkisti.zekeridou@unige.ch

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: The examiner, the biostatistician and people working in the laboratory for the analyses, will be blinded for the allocation group. Only the two operators and the participants will be aware of the type of treatment based on the computer-generated allocation table that will be kept at the Trial Master File (TMF) of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomized, 3-arm parallel group, single-blind, comparative superiority and exploratory clinical trial with 1:1 allocation ratio.

Study Record Dates

• First Submitted: November 20, 2020
• First Posted: December 17, 2020
• Study Start: September 1, 2021
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)