Antibiotics for Gum Disease

(PAAS Trial)

Overseen By Varvara Chrepa, DDS, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Antibiotics, Disulfiram, Warfarin, others

Disqualifiers: Drug allergy, Recent antibiotics, Immunocompromised, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 10 days

544 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have used systemic antibiotics in the last 3 months or if you are taking medications that might interact with the trial antibiotics, like disulfiram, warfarin, or oral contraceptives.

What data supports the effectiveness of the drug Amoxicillin / Metronidazole for treating gum disease?

Research shows that using amoxicillin and metronidazole together can help improve the treatment of aggressive gum disease by reducing harmful bacteria and improving gum health. ^{1 2 3 4 5}

Is the combination of amoxicillin and metronidazole safe for humans?

A study analyzing five clinical trials found that there are side effects associated with taking amoxicillin and metronidazole, but it did not specify the nature or severity of these side effects. ^{4 6 7 8 9}

How does the drug amoxicillin plus metronidazole differ from other treatments for gum disease?

Amoxicillin plus metronidazole is unique because it targets specific bacteria associated with gum disease, particularly in patients with certain microbiologic profiles, and is used alongside standard cleaning procedures to enhance treatment effectiveness. ^{1 5 7 8 10}

What is the purpose of this trial?

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.

Research Team

Georgios Kotsakis, DDS

Principal Investigator

Rutgers University

Eligibility Criteria

This trial is for adults at least 40 years old in good general health with generalized stage II-III, grades A-C periodontitis. They must have ≥20 permanent teeth and be willing to undergo treatment and follow-up for 12-15 months. Participants will come from National Dental PBRN practices.

Inclusion Criteria

I have at least 20 permanent teeth, not counting wisdom teeth.

I am 40 years old or older.

Willing to comply with all study visits and be available for the duration of the study (12-15 months)

Exclusion Criteria

Known drug allergy to any antibiotics or anesthetics

Is currently pregnant or lactating

I need antibiotics before any dental work due to a medical condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive scaling and root planing (SRP) with either adjunctive antibiotics (Amoxicillin and Metronidazole) or placebo

10 days

1 visit (in-person) for loading dose, followed by self-administration

Re-evaluation

Participants are assessed for changes in periodontal clinical and patient-reported outcomes

6 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

1 visit (in-person)

Treatment Details

Interventions

• Amoxicillin / Metronidazole

Trial Overview The study tests the effectiveness of using antibiotics Amoxicillin/Metronidazole alongside scaling and root planing (SRP) compared to SRP with a placebo in treating gum disease. It's a large-scale, randomized, controlled trial involving about 544 patients across various dental practices.

Participant Groups

Group I: Test Arm Experimental Treatment 2 Interventions

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.

Group II: Control Arm Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

National Institute of Dental and Craniofacial Research (NIDCR)

Collaborator

Trials

312

Recruited

853,000+

National Dental PBRN

Collaborator

Trials

1

Recruited

540+

Findings from Research

In a study of 42 patients with generalized aggressive periodontitis, the use of adjunctive amoxicillin and metronidazole (AMX + MET) during or after scaling and root planing (SRP) significantly improved periodontal outcomes, particularly in reducing pocket probing depth (PD).

The effectiveness of nonsurgical periodontal treatment was primarily influenced by site-level factors, with deeper initial PD and intrabony defects showing greater improvement, while persistent infections and tooth mobility negatively impacted treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multilevel Analysis of Non-surgical Periodontal Treatment of Patients with Generalised Aggressive Periodontitis. Lu, RF., Xu, L., Feng, XH., et al.[2021]

In a study of 102 patients with severe chronic periodontitis, the addition of a 3 or 7-day course of amoxicillin and metronidazole to non-surgical periodontal treatment resulted in significantly greater reductions in probing pocket depth compared to placebo, indicating enhanced efficacy of the antibiotic regimen.

Both the 3-day and 7-day antibiotic treatments led to statistically significant clinical improvements in periodontal health, demonstrating that systemic antibiotics can effectively support non-surgical periodontal therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-surgical periodontal treatment in conjunction with 3 or 7 days systemic administration of amoxicillin and metronidazole in severe chronic periodontitis patients. A placebo-controlled randomized clinical study. Cosgarea, R., Juncar, R., Heumann, C., et al.[2018]

A systematic review of six randomized clinical trials showed that the combination of amoxicillin and metronidazole significantly improves clinical parameters in patients with stage II - III grade C periodontitis, particularly in moderate and severe pockets.

For optimal efficacy in clinical attachment level gain, higher doses of metronidazole (400 to 500 mg) are recommended as an adjunct to scaling and root planning treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amoxicillin/Metronidazole Dose Impact as an Adjunctive Therapy for Stage II - III Grade C Periodontitis (Aggressive Periodontitis) at 3- And 6-Month Follow-Ups: a Systematic Review and Meta-Analysis. Karrabi, M., Baghani, Z.[2022]

In a study involving 15 individuals with aggressive periodontitis, non-surgical periodontal treatment combined with antibiotics (amoxicillin and metronidazole) significantly improved most clinical parameters after three months, except for clinical attachment level (CAL).

The treatment also led to a significant reduction in harmful bacteria associated with periodontitis, specifically Tannerella forsythia and Treponema denticola, indicating its effectiveness in addressing the microbiological aspects of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and microbiologic evaluation, by real-time polymerase chain reaction, of non-surgical treatment of aggressive periodontitis associated with amoxicillin and metronidazole. Rodrigues, AS., Lourenção, DS., Lima Neto, LG., et al.[2015]

In a study of 82 participants with moderate to advanced periodontitis, those treated with amoxicillin plus metronidazole showed significantly fewer sites with deep probing depths and bleeding compared to the placebo group, indicating the efficacy of the antibiotic treatment.

The presence of Aggregatibacter actinomycetemcomitans did not influence the effectiveness of the antibiotics, suggesting that all patients benefited from the treatment, with molar sites showing a greater improvement than non-molar sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are there specific benefits of amoxicillin plus metronidazole in Aggregatibacter actinomycetemcomitans-associated periodontitis? Double-masked, randomized clinical trial of efficacy and safety. Mombelli, A., Cionca, N., Almaghlouth, A., et al.[2013]

In a review of five clinical trials involving 656 subjects, the combination of metronidazole and amoxicillin (MTZ + AMX) showed a side effect frequency ranging from 1.0% to 17.7%, with diarrhea and metallic taste being the most common adverse effects compared to placebo.

Factors such as diabetes, being female, and being under 49 years old significantly increased the likelihood of reporting side effects, particularly when antibiotics were taken during the healing phase after mechanical treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of metronidazole and amoxicillin: Retrospective analysis of a large data set of five randomized clinical trials. Retamal-Valdes, B., Tavares, APL., Monique, S., et al.[2022]

The study found that the combination of amoxicillin and metronidazole, administered systemically, achieves high concentrations in gingival connective tissue, significantly exceeding the minimum inhibitory concentration needed to combat periodontal pathogens.

After 7 days of treatment, amoxicillin levels in inflamed tissue reached 124.8 μg/mL, while metronidazole levels were 36.0 μg/mL, indicating effective drug distribution in both healthy and inflamed gingival tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local concentration of systemic amoxicillin and metronidazole in healthy and inflamed gingiva: a comparative in vivo study. Amid, R., Tabeie, MB., Kadkhodazadeh, M., et al.[2013]

This systematic review and meta-analysis evaluated the efficacy of amoxicillin-plus-metronidazole as an adjunct to nonsurgical periodontal therapy, analyzing randomized, placebo-controlled trials to determine optimal dosing and duration.

The findings suggest that the combination of these antibiotics can enhance treatment outcomes in periodontal therapy, although specific optimal doses and treatment durations were not detailed in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Amoxicillin (500 Mg) Plus Metronidazole (500 Mg) for 7 Days Adds Adjunctive Benefits for Nonsurgical Periodontal Therapy, but Limited Evidence Supports Higher/Longer Dose. Wang, JC.[2019]

In a study of 39 patients with generalized aggressive periodontitis, the combination of metronidazole and amoxicillin with the One-Stage-Full-Mouth-Disinfection protocol significantly improved clinical outcomes, such as probing depth and clinical attachment level, compared to a placebo group.

The test group also showed a notable reduction in harmful bacteria associated with periodontitis, including Aggregatibacter actinomycetemcomitans and Treponema denticola, indicating that this antibiotic combination effectively targets key pathogens in periodontal disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Full-mouth disinfection and systemic antimicrobial therapy in generalized aggressive periodontitis: a randomized, placebo-controlled trial. Aimetti, M., Romano, F., Guzzi, N., et al.[2022]

In a study of 30 subjects with generalized aggressive periodontitis, the combination of metronidazole and amoxicillin alongside scaling and root planing significantly improved clinical outcomes, including probing depth and clinical attachment, at 1 year post-treatment.

The adjunctive antibiotic therapy resulted in deeper reductions in probing depth and fewer residual sites with high probing depths compared to scaling and root planing alone, demonstrating its efficacy in enhancing non-surgical treatment for periodontitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of adjunctive metronidazole plus amoxicillin in the treatment of generalized aggressive periodontitis: a 1-year double-blinded, placebo-controlled, randomized clinical trial. Mestnik, MJ., Feres, M., Figueiredo, LC., et al.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Multilevel Analysis of Non-surgical Periodontal Treatment of Patients with Generalised Aggressive Periodontitis. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Non-surgical periodontal treatment in conjunction with 3 or 7 days systemic administration of amoxicillin and metronidazole in severe chronic periodontitis patients. A placebo-controlled randomized clinical study. [2018]

3. Lithuania pubmed.ncbi.nlm.nih.gov

Amoxicillin/Metronidazole Dose Impact as an Adjunctive Therapy for Stage II - III Grade C Periodontitis (Aggressive Periodontitis) at 3- And 6-Month Follow-Ups: a Systematic Review and Meta-Analysis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Clinical and microbiologic evaluation, by real-time polymerase chain reaction, of non-surgical treatment of aggressive periodontitis associated with amoxicillin and metronidazole. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Are there specific benefits of amoxicillin plus metronidazole in Aggregatibacter actinomycetemcomitans-associated periodontitis? Double-masked, randomized clinical trial of efficacy and safety. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Adverse events of metronidazole and amoxicillin: Retrospective analysis of a large data set of five randomized clinical trials. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Local concentration of systemic amoxicillin and metronidazole in healthy and inflamed gingiva: a comparative in vivo study. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

The Use of Amoxicillin (500 Mg) Plus Metronidazole (500 Mg) for 7 Days Adds Adjunctive Benefits for Nonsurgical Periodontal Therapy, but Limited Evidence Supports Higher/Longer Dose. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Full-mouth disinfection and systemic antimicrobial therapy in generalized aggressive periodontitis: a randomized, placebo-controlled trial. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

The effects of adjunctive metronidazole plus amoxicillin in the treatment of generalized aggressive periodontitis: a 1-year double-blinded, placebo-controlled, randomized clinical trial. [2013]