Clinical trial NCT06131021: Shaping the Indications for Periodontal Adjunctive Antibiotics in Dental Practice
Official title: Shaping the Indications for Periodontal Adjunctive Antibiotics in Dental Practice: A PBRN Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Periodontitis
Periodontal Diseases
Periodontal Pocket
Keywords: Antibiotics
Amoxicillin
Metronidazole
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: National Institute of Dental and Craniofacial Research (NIDCR)
name: National Dental PBRN
First posted: 2023-11-14
Enrollment: 544
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The sample size will be a target of approximately 544 patient participants enrolled from approximately 34 National Dental PBRN practices. All patient participants are indicated to receive SRP and have been diagnosed with periodontitis stages II-III, grades A-C. A double-blinded patient participant-randomized design is used to assign patient participants to SRP plus AMXM versus SRP plus placebo prior to treatment.
Primary purpose: TREATMENT

Brief summary: Periodontitis is a bacterial inflammatory disease and antibiotic use is being empirically used as part of its treatment. However, a clinical practice guideline on periodontal treatment adjuncts published in 2015 identified weak evidence on the use of systemic antibiotics and large heterogeneity across small scale studies, suggesting that larger pragmatic clinical trials would benefit clinical decision making. This will be a prospective, randomized, placebo-controlled trial, stratified by practice and practitioner. The study will investigate the effectiveness of adjunctive antibiotics as adjunct to scaling and root planing (SRP) compared to SRP with placebo for the treatment of generalized stage II-III, grades A-C periodontitis in approximately 544 patient participants from about 34 National Dental PBRN practices. Periodontal data will be collected at baseline, re-evaluation (6 weeks), and final (12 months) study visits. Changes in periodontal clinical and patient-reported outcomes will be assessed to determine the effectiveness of SRP plus adjunctive systemic Amoxicillin / Metronidazole antibiotics (AMXM) versus SRP with Placebo.

Detailed description: Précis: Periodontitis is a bacterial inflammatory disease and antibiotic use is being empirically used as part of its treatment. However, a clinical practice guideline on periodontal treatment adjuncts published in 2015 identified weak evidence on the use of systemic antibiotics and large heterogeneity across small scale studies, suggesting that larger pragmatic clinical trials would benefit clinical decision making. This will be a prospective, randomized, placebo-controlled trial, stratified by practice and practitioner. The study will investigate the effectiveness of adjunctive antibiotics as adjunct to scaling and root planing (SRP) compared to SRP with placebo for the treatment of generalized stage II-III, grades A-C periodontitis in approximately 544 patient participants from about 34 National Dental PBRN practices. Periodontal data will be collected at baseline, re-evaluation (6 weeks), and final (12 months) study visits. Changes in periodontal clinical and patient-reported outcomes will be assessed to determine the effectiveness of SRP plus adjunctive systemic Amoxicillin / Metronidazole antibiotics (AMXM) versus SRP with Placebo.

Objectives and Outcomes: Primary: The primary objective will assess the effectiveness of SRP plus adjunctive antibiotics compared to SRP with placebo in periodontitis individuals from baseline to 6 weeks and 12 months following non-surgical periodontal therapy (NSPT) as determined by changes in site-level periodontal probing depth (PD).

Secondary: To assess changes in: i) gingival inflammation (measured by bleeding on probing (BoP)), ii) periodontal tissue attachment (measured by clinical attachment level (CAL)), iii) reduction in diseased sites (measured by remaining sites with maximum probing depth ≥5 mm), and iv) disease remission (measured by number of participants with ≤4 sites with PD≥ 5mm); comparing SRP plus AMXM to SRP with a placebo adjunctive in periodontitis individuals from baseline to re-evaluation (6 weeks) to final (12 month) study visit following intervention. The patient-reported impact of periodontal treatment (measured by the Oral Health Impact Profile-5 (OHIP-5)) and treatment-related adverse events between groups will also be assessed.

Population: The sample size will be a target of approximately 544 patient participants enrolled from approximately 34 National Dental PBRN practices. All patient participants are indicated to receive SRP and have been diagnosed with periodontitis stages II-III, grades A-C.

Description of Intervention: The intervention will involve either SRP, which is considered the standard of care treatment for debriding root surfaces, in conjunction with 500 mg Amoxicillin and 500mg Metronidazole orally every 8 hours (q8h) for ten days following SRP or SRP with placebo.

Eligibility criteria: Inclusion Criteria:

* The study will recruit a target of 544 patient participants presenting for periodontal treatment within the National Dental PBRN practices participating in this study.

To be eligible to participate in this study, a potential patient participant must meet all the following criteria:

* Adult who is at least 40 years old.
* Presence of ≥ 20 permanent teeth excluding 3rd molars.
* In good general health as evidenced by medical history (ASA Class I or II) per the practitioner.
* Planned to receive periodontal care for Generalized Stage II-III, Grade A-C periodontitis (previously Generalized Moderate to Severe Periodontitis) and a minimum of two quadrants of SRP (CDT code 4341) in practices participating in the National Dental PBRN.
* Willing to comply with all study visits and be available for the duration of the study (12-15 months)
* Willing to provide contact information for self, including a cellular phone number for study text, and one to two emergency contacts to be reached for the follow-up visits and any other study-related matters for the duration of the study.

Exclusion Criteria:

* Known drug allergy to any antibiotics or anesthetics.
* Use of systemic antibiotics taken within the previous 3 months prior to enrollment.
* Medical condition which requires antibiotic prophylaxis prior to dental treatments/visits.
* Current use of medications that, in the opinion of the practitioner, may cause adverse effects with AMXM (such as disulfiram, warfarin, and oral contraceptives).
* History of any periodontal therapy (including SRP D4341, D4342) within the last 6 months prior to enrollment.
* Is currently pregnant or lactating per patient participant self-report.
* Is considered immunocompromised, in the opinion of the practitioner (including diseases and conditions such as HIV/AIDS, immunosuppressive drug therapy and/or radiation), or has chronic mucosal lesions (e.g. pemphigus vulgaris) affecting the gingiva.
* Has Diabetes mellitus with an HbA1c score of \>/= 10% within the past 3 months as per patient participant self-report.

Primary outcomes:
measure: Probing Depth (PD) in millimeters
timeFrame: Baseline, Re-evaluation (6 weeks), and Final study visit (12 months) after intervention.
Secondary outcomes:
measure: Clinical attachment level (CAL) in millimeters
timeFrame: Baseline, Re-evaluation (6 weeks), and Final study visit (12 months) after intervention.
measure: Changes in the probability of bleeding on probing (BoP)
timeFrame: Baseline, Re-evaluation (6 weeks), and Final study visit (12 months) after intervention.
measure: Reduction in diseased sites
timeFrame: Baseline, Re-evaluation (6 weeks), and Final study visit (12 months) after intervention.
measure: Disease remission
timeFrame: Baseline, Re-evaluation (6 weeks), and Final study visit (12 months) after intervention.
measure: Changes in oral health-related quality of life
timeFrame: Baseline, Re-evaluation (6 weeks), and Final study visit (12 months) after intervention.
Other outcomes:
measure: Treatment-related adverse events
timeFrame: Through study completion, an average of 12 months
Locations:
city: Birmingham
country: United States
facility: University of Alabame
state: Alabama
Study officials:
affiliation: Rutgers University
name: Georgios Kotsakis, DDS
role: PRINCIPAL_INVESTIGATOR
References: