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NCT Number: NCT04669717

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

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.

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Key information

Conditions

Periodontal Diseases Antibiotics Mouth Diseases Pharmacokinetics Stomatognathic Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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

Drug

Non-surgical periodontal therapy and radnomly administration of the antibiotics

Other names: AMOXICILLINE Sandoz cpr pell 500 mg, Sandoz Pharmaceuticals AG + FLAGYL cpr pell 500 mg, Sanofi-Aventis ( Suisse) SA

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

Drug

Non-surgical periodontal therapy and radnomly administration of the antibiotics

Other names: AMOXICILLINE Sandoz cpr pell 500 mg, Sandoz Pharmaceuticals AG + FLAGYL cpr pell 500 mg, Sanofi-Aventis ( Suisse) SA

1/d 500 mg Azithromycine Pfizer for 3 days

Drug

Non-surgical periodontal therapy and radnomly administration of the antibiotics

Other names: AZITHROMYCIN Pfizer cpr pell 500mg, Pfizer PFE Switzerland GmbH

Primary outcomes

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

    Time frame: At Day 0,2,4,8 post-dose

    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 outcomes

  1. 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.

    Time frame: At Month 3 and Month 6 post-intervention

    Comparisons between groups assessed at 3 and 6 months after treatment

  2. 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.

    Time frame: At Month 3 and Month 6 post-intervention

    Comparisons between groups will be assessed at 3 and 6 months after treatment

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

    Time frame: At Day 2, Day 4 and Day 8 post-intervention

    Adverse events will be collected from the start of study treatment and until the end of the study (at 6 months evaluation)

  4. Patient's compliance will be evaluated

    Time frame: At Day 8 after intervention

    Compliance will be evaluated by pill count at the end of the antibiotherapy.

Study contacts

Contact information is provided by the study sponsor or research team.

Alkisti Zekeridou, Dr med dent

CONTACT

[email protected]

0041223794031

Catherine Giannopoulou, Dr med dent

CONTACT

[email protected]

0041223794068

Sponsors and collaborators

Lead sponsor

University of Geneva, Switzerland

Other

Collaborators

  • University of Lausanne

Registry information

Official study 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.

Acronym: AMA

Important dates

Study start
2021
Primary completion
2028
Study completion
2028
First posted
Dec 17, 2020
Registry last updated
Apr 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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