Shaping the Indications for Periodontal Adjunctive Antibiotics in Dental Practice

NCT06131021 | Completed Phase 3 FDA Drug

• 2 other identifiers: Pro20230013474UH3DE031129-02
• Study Type: interventional
• Target: 236
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Periodontitis; Periodontal Diseases; Periodontal Pocket

Keywords

Antibiotics; Amoxicillin; Metronidazole

Outcome Measures

Primary Outcomes (1)

• Probing Depth (PD) in millimeters

  The primary outcome of treatment effectiveness will be assessed by full-mouth probing depth (PD) from baseline to 6 weeks following intervention. Full-mouth PD measurements (excluding 3rd molars) will be obtained utilizing a UNC 15mm periodontal probe.

  Baseline to Re-evaluation (6 weeks)

Secondary Outcomes (6)

• Clinical attachment level (CAL) in millimeters

  Baseline, Re-evaluation (6 weeks), and Final study visit (4-12 months) after intervention.

• Changes in the probability of bleeding on probing (BoP)

  Baseline, Re-evaluation (6 weeks), and Final study visit (4-12 months) after intervention.

• Reduction in diseased sites

  Baseline, Re-evaluation (6 weeks), and Final study visit (4-12 months) after intervention.

• Disease remission

  Baseline, Re-evaluation (6 weeks), and Final study visit (4-12 months) after intervention.

• Changes in oral health-related quality of life

  Baseline, Re-evaluation (6 weeks), and Final study visit (4-12 months) after intervention.

Other Outcomes (1)

• Treatment-related adverse events

  Through study completion, up to the 4-12 months final visit

Study Arms (2)

Test Arm

EXPERIMENTAL

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.

Drug: Amoxicillin; Drug: Metronidazole

Control Arm

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

Amoxicillin DRUG

Amoxicillin belongs to the penicillin category, and it is a commonly prescribed broad-spectrum antibiotic as a periodontal treatment adjunct.

Test Arm

Metronidazole DRUG

Metronidazole is effective against anaerobic bacteria, and it is often combined with Amoxicillin for an enhanced antimicrobial effect as a periodontal treatment adjunct.

Test Arm

Placebo OTHER

Placebo in identical drug-safe vials with capsules identical in appearance to the active drugs

Control Arm

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator
• National Dental PBRN: collaborator

Study Sites (1)

University of Alabame

Birmingham, Alabama, 35233, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Periodontitis; Periodontal Diseases; Periodontal Pocket

Interventions

Amoxicillin; Metronidazole

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Georgios Kotsakis, DDS

  Rutgers University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: PBRN practitioner- and patient participant-level masking. Statistician assessor will also remain blinded; a separate biostatistician will remain unblinded in order to implement randomization.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The sample size will be a target of approximately 214 patient participants enrolled from up to 34 National Dental PBRN practices. All patient participants are indicated to receive SRP and have been diagnosed with periodontitis. A double-blinded patient participant-randomized design is used to assign patient participants to SRP plus AMXM versus SRP plus placebo prior to treatment.

Study Record Dates

• First Submitted: October 31, 2023
• First Posted: November 14, 2023
• Study Start: April 25, 2024
• Primary Completion: April 7, 2026
• Study Completion: April 7, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)