Local and Systemic Antimicrobials in Non-surgical Periodontal Therapy

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05608564

Enrollment

Registered

2022-11-08

Start date

2023-01-17

Completion date

2024-03-11

Last updated

2025-07-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Periodontitis

Keywords

local antibiotics, systemic antibiotics

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.

Interventions

PROCEDUREPiperacillin and Tazobactam in gel form

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

PROCEDUREAmoxicillin and Metronidazole

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Intervention 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.

Eligibility

Sex/Gender

ALL

Age

18 Years to 45 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Change in Pocket Probing Depth (PPD)	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)	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)	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)	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 (%).

Secondary

Measure	Time frame	Description
Change in Total Bacterial Load (TBL)	baseline and 6 months follow up	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.
Changes in Relative Expression Levels of IL-17	baseline and 6 months follow up	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.
Changes in Relative Expression Levels of Tumor Necrois Factor Alpha (TNF-α)	baseline and 6 months follow up	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.

Countries

Serbia

Participant flow

Recruitment details

Of the 38 participants screened at the Department of Periodontology and Oral Medicine at the School of Dental Medicine University of Belgrade, 38 participants were enrolled

Pre-assignment details

All 38 participants who met the inclusion criteria were enrolled and directly assigned to study groups without a pre-assignment phase.

Participants by arm

Arm	Count
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. Piperacillin and Tazobactam in gel form: After non-surgical periodontal treatment, the test group will receive local antibiotics.	19
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. Amoxicillin and Metronidazole: After non-surgical periodontal treatment, the control group will receive systemic antibiotics.	19
Total	38

Baseline characteristics

Characteristic	Local Antibiotic Group	Systemic Antibotic Group	Total
Age, Continuous	33.59 years	36.06 years	34.83 years
BOP baseline	0.6311 percentage STANDARD_DEVIATION 0.1214	0.6794 percentage STANDARD_DEVIATION 0.1861	0.655 percentage STANDARD_DEVIATION 0.157
CAL baseline	4.4 mm STANDARD_DEVIATION 0.8452	4.494 mm STANDARD_DEVIATION 0.7677	4.447 mm STANDARD_DEVIATION 0.8088
IL-17	0.008072 ng/mL STANDARD_DEVIATION 0.004611	0.007164 ng/mL STANDARD_DEVIATION 0.008121	0.00762 ng/mL STANDARD_DEVIATION 0.00653
PI baseline	0.6537 percentage STANDARD_DEVIATION 0.1283	0.7041 percentage STANDARD_DEVIATION 0.2525	0.670 percentage STANDARD_DEVIATION 0.119
PPD baseline	3.932 mm STANDARD_DEVIATION 0.5355	4.082 mm STANDARD_DEVIATION 0.5812	4.007 mm STANDARD_DEVIATION 0.556
Race and Ethnicity Not Collected	—	—	0 Participants
Region of Enrollment Serbia	19 participants	19 participants	38 participants
Sex: Female, Male Female	11 Participants	12 Participants	23 Participants
Sex: Female, Male Male	8 Participants	7 Participants	15 Participants
TBL	1.87 CFU/mL STANDARD_DEVIATION 5.44	1.79 CFU/mL STANDARD_DEVIATION 5.54	1.80 CFU/mL STANDARD_DEVIATION 5.42
TNF-α	0.03347 ng/mL STANDARD_DEVIATION 0.01475	0.05048 ng/mL STANDARD_DEVIATION 0.06895	0.042 ng/mL STANDARD_DEVIATION 0.05

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 19	0 / 19
other Total, other adverse events	0 / 19	0 / 19
serious Total, serious adverse events	0 / 19	0 / 19

Outcome results

Primary

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 (%).

Time frame: baseline and 6 months follow up