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

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether antibiotics, taken alongside standard dental cleaning procedures, can better treat gum disease. The focus is on individuals with generalized periodontitis, a condition where gums become inflamed due to bacteria. Participants will receive either antibiotics (Amoxicillin and Metronidazole) or a placebo during their regular gum treatment to determine if antibiotics make a difference. Suitable candidates have at least 15 permanent teeth and plan to undergo gum treatment involving scaling and root planing. The study aims to clarify whether antibiotics can effectively enhance typical gum care routines. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in dental care.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that taking amoxicillin and metronidazole together is usually safe for treating gum disease. Studies have found that this antibiotic combination effectively treats periodontitis (a gum infection) and reduces harmful bacteria when used with deep gum cleaning. Some people might experience mild side effects like an upset stomach or diarrhea, but these are generally not serious. This treatment is widely used and considered safe for many. However, discussing any concerns with a healthcare provider before starting the treatment is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for gum disease?

Researchers are excited about using Amoxicillin and Metronidazole for gum disease because this combination targets the bacterial infection directly, a different approach than typical treatments like scaling and root planing alone. This antibiotic combo is taken orally, providing a systemic effect that could enhance the healing process by reducing bacterial load more effectively than localized treatments. Additionally, the use of a loading dose before periodontal treatment could lead to quicker and more substantial improvements, potentially reducing the time needed for noticeable results.

What evidence suggests that this trial's treatments could be effective for gum disease?

In this trial, participants in the test arm will receive a combination of the antibiotics amoxicillin and metronidazole alongside their regular dental cleanings to help manage gum disease. Research has shown that adding these antibiotics can significantly improve the treatment of periodontitis, especially when used with scaling and root planing, a common gum treatment. Specifically, patients who took these antibiotics with their cleanings experienced better short-term results. Evidence also suggests that this treatment is effective for people without other health issues affecting their gums. Overall, these antibiotics appear promising for improving gum health when combined with standard treatments. ^{1 2 6 7 8}

Who Is on the Research Team?

Georgios Kotsakis, DDS

Principal Investigator

Rutgers University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9069637/

Amoxicillin/Metronidazole Dose Impact as an Adjunctive ... Amoxicillin/metronidazole has positive short-term effects as an adjunct to scaling and root planning for treatment of stage II - III grade C periodontitis.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9695465/

Efficacy of Systemic Amoxicillin–Metronidazole in ... Systemic amoxicillin–metronidazole was proven to be effective in managing periodontitis in systemically healthy patients.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02954393

Amoxicillin and Metronidazole During Periodontal Treatment The combination of systemic metronidazole (MTZ) and amoxicillin (AMX) to scaling and root planing (SRP) has shown to be a promising periodontal treatment.

4. sciencedirect.com sciencedirect.com/science/article/pii/S153233821300047X

The 1-Year Treatment Outcome of Generalized Chronic ... Studies show that these medications, including amoxicillin and metronidazole5, 6 and clarithromycin and others, contribute to a significant improvement in the ...

5. cureus.com cureus.com/articles/350401-the-effectiveness-of-metronidazole-as-a-localized-drug-delivery-system-in-the-treatment-of-periodontal-diseases-a-narrative-review

The Effectiveness of Metronidazole as a Localized Drug ... Metronidazole and amoxicillin yield positive results when used with scaling and root planing [36,37]. Metronidazole is a notable pharmacological ...

6. mdpi.com mdpi.com/1648-9144/58/11/1605

Efficacy of Systemic Amoxicillin–Metronidazole in ... Systemic amoxicillin–metronidazole was proven to be effective in managing periodontitis in systemically healthy patients.

7. withpower.com withpower.com/trial/phase-3-periodontitis-3-2024-31643

Antibiotics for Gum Disease (PAAS Trial) Research shows that using amoxicillin and metronidazole together can help improve the treatment of aggressive gum disease by reducing harmful bacteria and ...

8. cureus.com cureus.com/articles/341290-targeted-use-of-antimicrobials-in-periodontal-therapy

Targeted Use of Antimicrobials in Periodontal Therapy Given its proven efficacy, the amoxicillin-metronidazole combination remains the preferred regimen for treating aggressive periodontitis.