Local and Systemic Antimicrobials in Non-surgical Periodontal Therapy

February 29, 2024 updated by: Iva Milinkovic, University of Belgrade

The Impact of Local vs. Systemic Adjuvant Antibiotics During Non-surgical Periodontitis Therapy on Clinical Parameters, Bacterial Count and Cytokine Levels - a Randomized Clinical Trial

The main treatment of every patient with periodontitis is non-surgical periodontal treatment (NSPT) with the ultimate goal to arrest inflammation. Given the biofilm microorganisms associated etiology of the periodontitis, NSPT can be combined with adjunctive antimicrobial therapy. Hence, this randomized clinical trial aims to compare the clinical and microbiological effectiveness and relative expression levels (REL) of proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17) between local and systemic antibiotics as adjunctive therapy to NSPT in patents with periodontitis stages 3.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study protocol:

This randomized clinical study will include 40 patients diagnosed with periodontitis stages 2 and 3. The investigation will be conducted at the Department of Periodontology and Oral Medicine, at the School of Dental Medicine, University of Belgrade. The laboratory part of the research will be carried out at the Department of Human genetics, at the School of Dental Medicine, University of Belgrade. Patients will be divided into two groups. The test group will consist of 20 patients who will be prescribed a local antibiotic (LA group), while the control group will consist of 20 patients who will be prescribed systemic antibiotic therapy (SA group). The division of patients into groups will be done with randomization envelopes after the diagnostic procedure.

Upon clinical examination, clinical periodontal parameters such as periodontal probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI) will be recorded for each patient around every tooth. Previous to treatment, subgingival crevicular fluid will be sampled with paper points from periodontal pockets for laboratory analysis.

Sampling will be performed as follows: first, a relatively dry working field will be established using paper water rollers and air jets, and then 3 paper points (number 30 - marked in blue) will be applied for 30 seconds in the periodontal pocket area of the selected premolar/molar tooth with a depth of more than 5mm. The procedure will be repeated immediately in the same region, to obtain duplicate samples. After that, the paper points will be placed in Eppendorf tubes and immediately transported to the basic research laboratory, where they will be stored at a temperature of -80 degrees Celsius and where microbiological and molecular analyses will be carried out.

After sampling, all patients will undergo a non-surgical phase of periodontal therapy, following a Full-mouth disinfection protocol. Six months after the NSPT, at the follow-up, clinical examination, detection of clinical parameters, and sampling procedure will be repeated. In the LA group, antibiotics will be applied after the NSPT, while in the SA group therapy will be prescribed at the beginning of the treatment. Locally will be applied a combination of piperacillin and tazobactam in gel form (Gelcide ®, Italmed MedTechDental, Florence, Italy) designed for use in the subgingival region. The local antibiotic will be applied into the periodontal pockets, using a syringe and a flexible blunt needle, 24 hours after the NSPT. The administration will be done by quadrants, following the principles of a dry work field, and after application, the dry field should be maintained for 5 minutes. After this procedure, the patient should not rinse the oral cavity for 15 minutes. For systemic use in the SA group, patients will receive a combination of Amoxicillin (Amoxicillin ®, 500mg, 3 times a day, 7 days) and Metronidazole (Orvagyl ®, 400mg, 3 times a day, 7 days) for oral use.

Total bacterial count (TBC) and REL of proinflammatory cytokines TNF-α and IL-17 will be detected using the quantitative real-time polymerase chain reaction (qPCR) in a basic research laboratory at the Department of Human genetics, at the School of Dental Medicine, University of Belgrade.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Serbia
      • Belgrade, Serbia, 11000
        • Department of Periodontology, School of Dental Medicine, University of Belgrade

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Both sexes, 18 - 45 years old
  2. Willingness to participate in the research, comply with all the study protocols, and sign an informed consent;
  3. Active periodontitis stage II and III according to the criteria of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions;
  4. Non-smokers and light smokers (up to 10 cigarettes per day).

Exclusion Criteria:

  1. Presence of systemic diseases known to affect the tooth-supporting apparatus and bone metabolism (such as uncontrolled diabetes mellitus, cancer, immunodeficiency, metabolic bone diseases);
  2. Patients receiving an immunosuppressive, anti-resorptive, or anti-inflammatory therapy;
  3. Allergy to penicillin;
  4. Patients who had undergone periodontal therapy within the last 6 months;
  5. Use of local and/or systemic antimicrobial agents within the last 6 months;
  6. Use of oral anti-plaque mouthwash at least one month prior to the study;
  7. Alcohol or drug abuse;
  8. Pregnancy or lactation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Local antibiotic group
A combination of Piperacillin and Tazobactam in gel form is applied using a syringe and a flexible blunt needle into the periodontal pockets 24 hours after the non-surgical periodontal therapy. After administration, the dry field should be maintained for 5 minutes and the patient should not rinse the oral cavity for 15 minutes.
Procedure: Piperacillin and Tazobactam in gel form
After non-surgical periodontal treatment, the test group will receive local antibiotics.
Other Names:
  • Gelcide
Active Comparator: Systemic antibotic group
Amoxicillin (500mg, 3 times a day, 7 days) and Metronidazole (400mg, 3 times a day, 7 days) per os at the beginning of non-surgical treatment.
Procedure: Amoxicillin and Metronidazole
After non-surgical periodontal treatment, the control group will receive systemic antibiotics.
Other Names:
  • Amoxicillin and Orvagyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Local antimicrobials comparable to systemic according to periodontal clinical parameters
Time Frame: 6 months
A significant change in clinical parameters such as probing depth, clinical attachment level, bleeding on probing, and plaque index is expected after both therapies in a similar matter. It will be detected with the periodontal probe in mm initially and at the follow-up clinical examination 3 months after the initial.
6 months
Local antimicrobials comparable to systemic according to total bacterial load
Time Frame: 6 months
Lower total bacteria number after prescription of both systemic and local antibiotics is expected to be proved by analyzing samples of crevicular fluid from pockets using the quantitative real-time polymerase chain reaction (qPCR).
6 months
Local antimicrobials comparable to systemic according to cytokine levels
Time Frame: 6 months
Lower relative expression levels of proinflammatory cytokines TNF-α and IL-17 are expected after both systemic and local antibiotics. They will be assessed by analyzing samples of crevicular fluid from pockets detected by using the quantitative real-time polymerase chain reaction (qPCR).
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Belgrade

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 17, 2022

Primary Completion (Actual)

August 31, 2022

Study Completion (Actual)

May 30, 2023

Study Registration Dates

First Submitted

October 24, 2022

First Submitted That Met QC Criteria

October 31, 2022

First Posted (Actual)

November 8, 2022

Study Record Updates

Last Update Posted (Estimated)

March 4, 2024

Last Update Submitted That Met QC Criteria

February 29, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22.10.1980

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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