Local and Systemic Antimicrobials in Non-surgical Periodontal Therapy

NCT ID: NCT05608564

Last Updated: 2025-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-17
• Study Completion Date: 2024-03-11

Brief Summary

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 stage 3.

Detailed Description

Study protocol:

This randomized clinical study will include 40 patients diagnosed with periodontitis stage 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 (PPD), 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.

Conditions

Periodontitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Piperacillin and Tazobactam in gel form

Intervention Type: PROCEDURE

After non-surgical periodontal treatment, the test group will receive local antibiotics.

Systemic antibiotic 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.

Group Type: ACTIVE_COMPARATOR

Amoxicillin and Metronidazole

Intervention Type: PROCEDURE

After non-surgical periodontal treatment, the control group will receive systemic antibiotics.

Interventions

Piperacillin and Tazobactam in gel form

After non-surgical periodontal treatment, the test group will receive local antibiotics.

Intervention Type: PROCEDURE

Amoxicillin and Metronidazole

After non-surgical periodontal treatment, the control group will receive systemic antibiotics.

Intervention Type: PROCEDURE

Other Intervention Names

Gelcide; Amoxicillin and Orvagyl

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Belgrade

OTHER

Sponsor Role: lead

Responsible Party

Iva Milinkovic

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Iva Z Milinkovic, DDS, PhD

Role: PRINCIPAL_INVESTIGATOR

School of Dental Medicine, University of Belgrade, Department of Periodontology and Oral Medicine

Locations

Department of Periodontology, School of Dental Medicine, University of Belgrade

Belgrade, , Serbia

Countries

Serbia

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

22.10.1980

Identifier Type: -

Identifier Source: org_study_id