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

Primary Purpose

Periodontal Diseases, Antibiotics, Pharmacokinetics

Status
Recruiting
Phase
Phase 4
Locations
Switzerland
Study Type
Interventional
Intervention
3/d 500 mg Amoxicilline Sandoz plus 500 mg Flagyl for 7 days
3/d 500 mg Amoxicilline Sandoz plus 500 mg Flagyl for 3 days
1/d 500 mg Azithromycine Pfizer for 3 days
Sponsored by
University of Geneva, Switzerland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Periodontal Diseases

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • University of Geneva, University Clinics of Dental MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Amoxicilline and Metronidazole for 7 days

Amoxicilline and Metronidazole for 3 days

Azithromycine for 3 days

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
Comparisons between groups assessed at 3 and 6 months after treatment
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.
Comparisons between groups will be assessed at 3 and 6 months after treatment
Number of participant per treatment arm with adverse events as a mesure of safety.
Adverse events will be collected from the start of study treatment and until the end of the study (at 6 months evaluation)
Patient's compliance will be evaluated
Compliance will be evaluated by pill count at the end of the antibiotherapy.

Full Information

First Posted
November 20, 2020
Last Updated
November 1, 2022
Sponsor
University of Geneva, Switzerland
Collaborators
University of Lausanne
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1. Study Identification

Unique Protocol Identification Number
NCT04669717
Brief Title
Antibiotics as Adjuncts to Periodontal Therapy:Pharmacokinetic Considerations and Dosing Strategies
Acronym
AMA
Official Title
Pharmacokinetic Considerations and Dosing Strategies of Amoxicillin and Metronidazole or Azithromycin as Adjunct to Non-surgical Periodontal Therapy. A Randomized,6-month, Parallel-group, Clinical Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2021 (Actual)
Primary Completion Date
March 1, 2024 (Anticipated)
Study Completion Date
March 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Geneva, Switzerland
Collaborators
University of Lausanne

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
This is a randomized, 3-arm parallel group, single-blind, comparative superiority and exploratory clinical trial of 44 months involving 45 patients with periodontitis attending the Division of Regenarative Dental Medecine and Periodontology of the University of Geneva. First, a routine clinical and radiographic periodontal examination will be conducted by a periodontist. Treatment will be done in 2 appointments by mechanical debridement of the diseased sites by two experienced clinicians. At the end of the treatment, one third of the patients will be assigned for treatment with 500mgAMO+ 500mgMET 3 times a day during 1 week, one third for treatment with 500mgAMO+ 500mgMET 3 times a day during 3 days and the last third for treatment with 500mg AZI once a day for 3 days. Clinical samples will be taken at Days 0, 2, 4 and 8 after the start of the antibiotic administration . Gingival Crevicular Fluid (GCF) will be collected from four sites with paperpoints, blood sample by finger puncture, unstimulated saliva and subgingival plaque from four sites with paper points. The concentration and duration effect of AMO+MET and AZI in GCF, saliva and serum will be assessed in the Laboratory of Clinical Pharmacology at the University Hospital of Lausanne (CHUV) by high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The microbiological effect on 6 selected organisms will be assessed by RT-PCR at 3 and 6 months after treatment. The clinical results will be evaluated 6 months later. The study duration for the patient will be approximately 8 months. All adverse events (AE) and all serious adverse events (SAEs) will be recorded and addressed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Periodontal Diseases, Antibiotics, Pharmacokinetics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Randomized, 3-arm parallel group, single-blind, comparative superiority and exploratory clinical trial with 1:1 allocation ratio.
Masking
Investigator
Masking Description
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.
Allocation
Randomized
Enrollment
45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Amoxicilline and Metronidazole for 7 days
Arm Type
Active Comparator
Arm Description
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
Arm Title
Amoxicilline and Metronidazole for 3 days
Arm Type
Active Comparator
Arm Description
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
Arm Title
Azithromycine for 3 days
Arm Type
Active Comparator
Arm Description
Drug: AZITHROMYCIN Pfizer cpr pell 500mg, Pfizer PFE Switzerland GmbH 1/d 500mg for 3 days Systemic antibiotics after sub gingival mechanical debridement
Intervention Type
Drug
Intervention Name(s)
3/d 500 mg Amoxicilline Sandoz plus 500 mg Flagyl for 7 days
Other Intervention Name(s)
AMOXICILLINE Sandoz cpr pell 500 mg, Sandoz Pharmaceuticals AG + FLAGYL cpr pell 500 mg, Sanofi-Aventis ( Suisse) SA
Intervention Description
Non-surgical periodontal therapy and radnomly administration of the antibiotics
Intervention Type
Drug
Intervention Name(s)
3/d 500 mg Amoxicilline Sandoz plus 500 mg Flagyl for 3 days
Other Intervention Name(s)
AMOXICILLINE Sandoz cpr pell 500 mg, Sandoz Pharmaceuticals AG + FLAGYL cpr pell 500 mg, Sanofi-Aventis ( Suisse) SA
Intervention Description
Non-surgical periodontal therapy and radnomly administration of the antibiotics
Intervention Type
Drug
Intervention Name(s)
1/d 500 mg Azithromycine Pfizer for 3 days
Other Intervention Name(s)
AZITHROMYCIN Pfizer cpr pell 500mg, Pfizer PFE Switzerland GmbH
Intervention Description
Non-surgical periodontal therapy and radnomly administration of the antibiotics
Primary Outcome Measure Information:
Title
The concentration of AMO+MET and AZI in GCF, saliva and serum
Description
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
Time Frame
At Day 0,2,4,8 post-dose
Secondary Outcome Measure Information:
Title
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.
Description
Comparisons between groups assessed at 3 and 6 months after treatment
Time Frame
At Month 3 and Month 6 post-intervention
Title
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.
Description
Comparisons between groups will be assessed at 3 and 6 months after treatment
Time Frame
At Month 3 and Month 6 post-intervention
Title
Number of participant per treatment arm with adverse events as a mesure of safety.
Description
Adverse events will be collected from the start of study treatment and until the end of the study (at 6 months evaluation)
Time Frame
At Day 2, Day 4 and Day 8 post-intervention
Title
Patient's compliance will be evaluated
Description
Compliance will be evaluated by pill count at the end of the antibiotherapy.
Time Frame
At Day 8 after intervention

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Catherine Giannopoulou, Dr med dent
Phone
0041223794068
Email
ekaterini.giannopoulou@unige.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Alkisti Zekeridou, Dr med dent
Phone
0041223794031
Email
alkisti.zekeridou@unige.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Catherine Giannopoulou, Dr med dent
Organizational Affiliation
University Clinics of Dental Medicine, University of Geneva
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Geneva, University Clinics of Dental Medicine
City
Geneva
ZIP/Postal Code
1205
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Catherine Giannopoulou, Dr med dent
Phone
022 379 40 68
Email
ekaterini.giannopoulou@unige.ch
First Name & Middle Initial & Last Name & Degree
Alkisti Zekeridou, Dr med dent
Phone
022 379 40 30
Email
alkisti.zekeridou@unige.ch

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
26604272
Citation
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.
Results Reference
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Antibiotics as Adjuncts to Periodontal Therapy:Pharmacokinetic Considerations and Dosing Strategies

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