PeriodontitisNCT05608564
Local and Systemic Antimicrobials in Non-surgical Periodontal Therapy
A study testing Piperacillin and Tazobactam in gel form and Amoxicillin and Metronidazole in people with Periodontitis, run by University of Belgrade at 1 site in Serbia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Periodontitis
- What is being tested?
- Piperacillin and Tazobactam in gel form and Amoxicillin and Metronidazole
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteSerbia
- Study dates
- 17 Jan 2023to 11 Mar 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Both sexes, 18 - 45 years old
- Willingness to participate in the research, comply with all the study protocols, and sign an informed consent;
- 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;
- Non-smokers and light smokers (up to 10 cigarettes per day).
Who cannot join
- Presence of systemic diseases known to affect the tooth-supporting apparatus and bone metabolism (such as uncontrolled diabetes mellitus, cancer, immunodeficiency, metabolic bone diseases);
- Patients receiving an immunosuppressive, anti-resorptive, or anti-inflammatory therapy;
- Allergy to penicillin;
- Patients who had undergone periodontal therapy within the last 6 months;
- Use of local and/or systemic antimicrobial agents within the last 6 months;
- Use of oral anti-plaque mouthwash at least one month prior to the study;
- Alcohol or drug abuse;
- Pregnancy or lactation.
Trial locations and contacts
1 site in 1 country.
Serbia1 site
Department of Periodontology, School of Dental Medicine, University of Belgrade
Belgrade, 11000
About this study
Official title: 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 stage 3.
Read the 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
- Being tested
- Piperacillin and Tazobactam in gel form, Amoxicillin and Metronidazole
- Keywords
- local antibiotics, systemic antibiotics
- Medical subject headings
- Periodontitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Piperacillin and Tazobactam in gel formProcedure or surgery
Also called Gelcide
After non-surgical periodontal treatment, the test group will receive local antibiotics.
Amoxicillin and MetronidazoleProcedure or surgery
Also called Amoxicillin and Orvagyl
After non-surgical periodontal treatment, the control group will receive systemic antibiotics.
| Study group | Role | What they receive |
|---|---|---|
| Local antibiotic group | Experimental | 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. Receives: Procedure: Piperacillin and Tazobactam in gel form |
| Systemic antibiotic group | Active comparator | 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. Receives: Procedure: Amoxicillin and Metronidazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pocket Probing Depth (PPD)
Pocket probing depth (PPD) was measured using a periodontal probe at 6 sites per tooth, recorded in millimeters (mm), at baseline and at 6-month follow-up. This measure was used to compare outcomes between local and systemic antimicrobial therapies.
Measured: baseline and 6 months follow up
Change in Clinical Attachment Level (CAL)
Pocket probing depth (PPD) was measured using a periodontal probe at 6 sites per tooth, recorded in millimeters (mm), at baseline and at 6-month follow-up. This measure was used to compare outcomes between local and systemic antimicrobial therapies.
Measured: baseline and 6 months follow up
Change in Bleeding On Probing (BOP)
Bleeding on probing (BOP) was assessed using a periodontal probe at 6 sites around each present tooth during baseline and 6-month follow-up clinical examinations. BOP was recorded as present (1) or absent (0) at each site, and expressed as a percentage (%).
Measured: baseline and 6 months follow up
Change in Plaque Index (PI)
Plaque Index (PI) was assessed using a periodontal probe at 6 sites around each present tooth during baseline and 6-month follow-up clinical examinations. BOP was recorded as present (1) or absent (0) at each site, and expressed as a percentage (%).
Measured: baseline and 6 months follow up
Secondary outcomes (3)
Changes in Relative Expression Levels of Tumor Necrois Factor Alpha (TNF-α)
Relative expression levels (REL) of TNF-α were assessed in gingival crevicular fluid (GCF) samples collected from periodontal pockets at baseline and 6-month follow-up. GCF was obtained using sterile paper strips, and TNF-α levels were quantified using the real-time polymerase chain reaction (qPCR) method. Results were expressed in nanograms per milliliter (ng/mL) to compare local and systemic antimicrobial therapy groups.
Measured: baseline and 6 months follow up
Change in Total Bacterial Load (TBL)
Total bacterial load (TBL) was assessed in gingival crevicular fluid (GCF) samples collected from periodontal pockets at baseline and at the 6-month follow-up. GCF was obtained using sterile paper strips, and bacterial quantification was performed using the real-time polymerase chain reaction (qPCR) method. Results were expressed in colony-forming units per milliliter (CFU/mL) to evaluate differences between local and systemic antimicrobial therapies.
Measured: baseline and 6 months follow up
Changes in Relative Expression Levels of IL-17
Relative expression levels (REL) of interleukin-17 (IL-17) were assessed in gingival crevicular fluid (GCF) samples collected from periodontal pockets at baseline and at the 6-month follow-up. GCF was obtained using sterile paper strips, and REL of IL-17 was quantified using the real-time polymerase chain reaction (qPCR) method. Results were expressed in nanograms per milliliter (ng/mL) to compare local and systemic antimicrobial therapies.
Measured: baseline and 6 months follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2022
- Study start17 Jan 2023
- Primary completion10 Aug 2023
- Study completion11 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PeriodontitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- After the non-surgical periodontal treatment, the test group will be treated with local antibiotics, while the control group will be treated with systemic antibiotics. Randomization will be performed using randomization envelopes.
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Belgrade
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Iva Milinkovic, University of Belgrade
- Investigators
- Iva Z Milinkovic, DDS, PhD, Principal investigator, School of Dental Medicine, University of Belgrade, Department of Periodontology and Oral Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05608564
- Sponsor's protocol ID
- 22.10.1980
- Status last verified
- Jul 2025
- First submitted
- 24 Oct 2022
- Last updated
- 17 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05608564
- Acronym / sponsor ID
- 22.10.1980
- Conditions
- Periodontitis
- Keywords
- local antibiotics, systemic antibiotics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- University of BelgradeUniversity, hospital or other
- Study start
- 17 Jan 2023 (actual)
- Primary completion
- 10 Aug 2023 (actual)
- Study completion
- 11 Mar 2024 (actual)
- First posted
- 8 Nov 2022 (actual)
- Results
- Posted 14 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- After the non-surgical periodontal treatment, the test group will be treated with local antibiotics, while the control group will be treated with systemic antibiotics. Randomization will be performed using randomization envelopes.
| Arm | Type | Receives |
|---|---|---|
| Local antibiotic group | Experimental | Procedure: Piperacillin and Tazobactam in gel formA 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. |
| Systemic antibiotic group | Active comparator | Procedure: Amoxicillin and MetronidazoleAmoxicillin (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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Both sexes, 18 - 45 years old
- Willingness to participate in the research, comply with all the study protocols, and sign an informed consent;
- 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;
- Non-smokers and light smokers (up to 10 cigarettes per day).
Key exclusion criteria (8 listed)
- Presence of systemic diseases known to affect the tooth-supporting apparatus and bone metabolism (such as uncontrolled diabetes mellitus, cancer, immunodeficiency, metabolic bone diseases);
- Patients receiving an immunosuppressive, anti-resorptive, or anti-inflammatory therapy;
- Allergy to penicillin;
- Patients who had undergone periodontal therapy within the last 6 months;
- Use of local and/or systemic antimicrobial agents within the last 6 months;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Piperacillin and Tazobactam in gel formAlso: GelcideAfter non-surgical periodontal treatment, the test group will receive local antibiotics. | Procedure or surgery | Local antibiotic group |
| Amoxicillin and MetronidazoleAlso: Amoxicillin and OrvagylAfter non-surgical periodontal treatment, the control group will receive systemic antibiotics. | Procedure or surgery | Systemic antibiotic group |
Primary outcome
Change in Pocket Probing Depth (PPD)
Time frame: baseline and 6 months follow up
Pocket probing depth (PPD) was measured using a periodontal probe at 6 sites per tooth, recorded in millimeters (mm), at baseline and at 6-month follow-up. This measure was used to compare outcomes between local and systemic antimicrobial therapies.
Change in Clinical Attachment Level (CAL)
Time frame: baseline and 6 months follow up
Pocket probing depth (PPD) was measured using a periodontal probe at 6 sites per tooth, recorded in millimeters (mm), at baseline and at 6-month follow-up. This measure was used to compare outcomes between local and systemic antimicrobial therapies.
Change in Bleeding On Probing (BOP)
Time frame: baseline and 6 months follow up
Bleeding on probing (BOP) was assessed using a periodontal probe at 6 sites around each present tooth during baseline and 6-month follow-up clinical examinations. BOP was recorded as present (1) or absent (0) at each site, and expressed as a percentage (%).
Change in Plaque Index (PI)
Time frame: baseline and 6 months follow up
Plaque Index (PI) was assessed using a periodontal probe at 6 sites around each present tooth during baseline and 6-month follow-up clinical examinations. BOP was recorded as present (1) or absent (0) at each site, and expressed as a percentage (%).
3 secondary outcomes
Changes in Relative Expression Levels of Tumor Necrois Factor Alpha (TNF-α)
Time frame: baseline and 6 months follow up
Change in Total Bacterial Load (TBL)
Time frame: baseline and 6 months follow up
Changes in Relative Expression Levels of IL-17
Time frame: baseline and 6 months follow up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Iva Z Milinkovic, DDS, PhD principal investigator
School of Dental Medicine, University of Belgrade, Department of Periodontology and Oral Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Piperacillin and Tazobactam in gel form and Amoxicillin and Metronidazole in people with Periodontitis, run by University of Belgrade at 1 site in Serbia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Pocket Probing Depth (PPD) (time frame: baseline and 6 months follow up). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2025.