Official Title: “Adjunctive Antimicrobial Therapy of Periodontitis: Long-Term Effects on Disease Progression and Oral Microbiological Colonization”

The purpose of this study is to determine the size of the benefit of an adjunctive empiric antibiotic therapy compared to standard mechanical debridement and oral hygiene instructions in a representative sample of German periodontitis patients.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: August 2011

Periodontitis is an endemic inflammatory disease caused by a mixed bacterial biofilm infection that is followed by destruction of tooth supporting tissues. Standard of care consists of lifelong mechanical removal of the biofilm. However, outcome is variable.

According to recent EFP and AAP reviews, adjunctive antimicrobial therapy may be beneficial.

We plan to conduct a double-blind, parallel group, randomized, placebo-controlled multi-center efficacy study that addresses the following objectives:

1. What is the size of the benefit of an adjunctive empiric antibiotic therapy compared to standard mechanical debridement and oral hygiene instructions in a representative sample of German periodontitis patients?

2. Does the administration of the antibiotic therapy delay recurrence of periodontitis in the general population and in specific high risk groups (e.g.

smokers) under standard supportive therapy?

3. Is the presence of specific microbial complexes a useful predictor of outcome and recurrence of periodontitis?

4. Does the administration of the antibiotic therapy affect the "oral health related quality of life"?

The primary hypothesis tested is: the administered empiric adjunctive antibiotic therapy reduces about one half of the proportion of sites with attachment loss compared to subgingival debridement alone over a 27.5-month period in a statistical and clinical significant manner.

To test this hypothesis about 500 patients will be enrolled in the clinical trial. According to the intention-to-treat principle, the primary efficacy analysis will include all randomized subjects. In addition, a per-protocol analysis will be done.

Intervention(s) in this Clinical Trial

• Drug: Amoxicillin and Metronidazole
  • tablets: Amoxicillin 3H2O 574 mg and 400 mg metronidazole three times daily for 7 days
• Drug: Placebo
  • Placebo tablets (cellulose powder, lactose monohydrate, magnesium stearate, microcrystalline cellulose): three times daily for 7 days

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: test
  • Mechanical debridement plus 500 mg amoxicillin and 400 mg metronidazole three times daily for 7 days. Supportive periodontal therapy in 3-month intervals.
• Placebo Comparator: control
  • Mechanical debridement plus two placebo tablets three times daily for 7 days. Supportive periodontal therapy in 3-month intervals.

Primary Measures

• Percentage of sites showing attachment loss ≥ 1.3 mm over a 27.5-months period
  • Time Frame: 27.5-months period (six measurements)
    Safety Issue?: No

Secondary Measures

• Subjective perception of treatment outcome, attachment gain, pocket probing depths, bleeding on probing, and full mouth plaque score. Microbial colonization dynamic.
  • Time Frame: over a 27.5-months period
    Safety Issue?: No

Inclusion Criteria:

• periodontal screening index (PSI) of IV in at least one sextant;
• range from 18 to 75 years of age;
• clinical and radiographic signs of moderate (clinical attachment loss [CAL] of 3 to 4 mm) to severe (CAL 5 mm or more) chronic or aggressive periodontitis;
• at least 10 natural teeth in situ;
• pocket probing depths (PPDs) of ≥ 6 mm at a minimum of four teeth;
• willingness to participate and to be available at all times required for participation;
• willingness to abstain from using antimicrobial mouth-rinses during the study except for those explicitly prescribed;
• informed consent signed by the patient;
• sufficient knowledge of German language.

Exclusion Criteria:

• if they (or parents or siblings) show confirmed or assumed allergies or hyper-sensitive skin reactions against amoxicillin (or other penicillins or other ingredients of Amoxicillin-ratiopharm® 500mg as listed in the "summary of product characteristics, Version Juli 2005"), metronidazole (or other 5-nitroimidazoles and ingredients of Flagyl® 400mg as listed in the "summary of product characteristics, Version Juli 2007"), systemic diseases or conditions as listed in the above mentioned
• "summary of product characteristics", or show confirmed lactose intolerance;
• have Down's syndrome;
• known AIDS/HIV;
• regularly take systemic medication affecting the periodontal conditions, e.g.
• phenytoin, nifedipine, and/or steroid drugs;
• professional periodontal therapy during 6 months prior to baseline;
• require antibiotic treatment for dental appointments;
• are undergoing or require extensive dental or orthodontic treatment;
• are pregnant or breastfeeding;
• have rampant caries;
• any oral or extraoral piercing in or around the oral cavity with ornaments or accessory jewelry;
• are dental students or dental professionals;
• have participated in a clinical dental trial in the six months preceding the study;
• cognitive deficits.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University Hospital Muenster

Overall Clinical Trial Officials and Contacts

Benjamin - Ehmke, PhD Principal Investigator University Hospital Muenster, Dept. of Periodontology  

Overall Contact: Benjamin - Ehmke, PhD 49-025-1834-7059 ehmke@uni-muenster.de

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00707369

Study ID Number: EH 365/1-1

ClinicalTrials.gov Identifier: NCT00707369

Health Authority: Germany: Federal Institute for Drugs and Medical Devices