Shaping the Indications for Periodontal Adjunctive Antibiotics in Dental Practice (PAAS)

Rutgers The State University of New Jersey

Status and phase: Enrolling; Phase 3

Conditions: Periodontitis; Periodontal Pocket; Periodontal Diseases

Treatments: Drug: Amoxicillin; Other: Placebo; Drug: Metronidazole

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06131021

4UH3DE031129-02 (U.S. NIH Grant/Contract)

Pro2023001347

Details and patient eligibility

About

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 patient participants from National Dental PBRN practices. Periodontal data will be collected at baseline, re-evaluation (6 weeks), and final (4-12 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.

Full 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 patient participants from National Dental PBRN practices. Periodontal data will be collected at baseline, re-evaluation (6 weeks), and final (4-12 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 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. Also, assess changes in periodontal probing depth from baseline measurements to final visit (4-12 months) 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: A sample size of 150 patient participants enrolled from up to 34 National Dental PBRN practices will be enrolled for adequate power. 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.

Enrollment: 150 estimated patients

Sex: All

Ages: 35+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• The study will recruit 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 35 years old.
• Presence of ≥ 15 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 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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150 participants in 2 patient groups, including a placebo group

Test Arm

Experimental group

Description:

Patient participants in this arm will receive a combination of Amoxicillin 500mg \& Metronidazole 500mg orally (AMXM) as adjuncts along with their scheduled non-surgical periodontal treatment as the study intervention. A loading dose of 1g of Amoxicillin and 1g of Metronidazole will be given 30-60 minutes prior to periodontal treatment. After the loading dose, each patient participant will be instructed to take Amoxicillin 500mg \& Metronidazole 500mg every 8 hours for 10 days.

Treatment:

Drug: Metronidazole

Drug: Amoxicillin

Control Arm

Placebo Comparator group

Description:

Patient participants in this arm will receive a placebo capsules identical to the study drug capsules along with their scheduled non-surgical periodontal treatment as the placebo comparator in an identical frequency and duration fashion as the active drug group.

Treatment:

Other: Placebo