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

NCT ID: NCT00707369

Last Updated: 2015-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 540 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2012-01-31

Brief Summary

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.

Detailed Description

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.

Conditions

Periodontitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

test

Mechanical debridement plus 500 mg amoxicillin and 400 mg metronidazole three times daily for 7 days. Supportive periodontal therapy in 3-month intervals.

Group Type: EXPERIMENTAL

Amoxicillin and Metronidazole

Intervention Type: DRUG

tablets: Amoxicillin 3H2O 574 mg and 400 mg metronidazole three times daily for 7 days

control

Mechanical debridement plus two placebo tablets three times daily for 7 days. Supportive periodontal therapy in 3-month intervals.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablets (cellulose powder, lactose monohydrate, magnesium stearate, microcrystalline cellulose): three times daily for 7 days

Interventions

Amoxicillin and Metronidazole

tablets: Amoxicillin 3H2O 574 mg and 400 mg metronidazole three times daily for 7 days

Intervention Type: DRUG

Placebo

Placebo tablets (cellulose powder, lactose monohydrate, magnesium stearate, microcrystalline cellulose): three times daily for 7 days

Intervention Type: DRUG

Other Intervention Names

Flagyl® 400 Filmtablette; Amoxicillin-ratiopharm® 500

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Muenster

OTHER

Sponsor Role: lead

Responsible Party

Benjamin Ehmke

Prof. Dr. med. dent.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Benjamin - Ehmke, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Muenster, Dept. of Periodontology

Locations

Medizinische Fakultät der Humboldt Universität Berlin (Charité)

Berlin, , Germany

Universitätsklinikum Carl Gustav Carus, Zentrum für Zahn-, Mund- und Kieferheilkunde

Dresden, , Germany

Zentrum der Zahn-, Mund- und Kieferheilkunde (Carolinum), Poliklinik für Parodontologie

Frankfurt, , Germany

Justus-Liebig-Universität Gießen, Poliklinik für Parodontologie

Giessen, , Germany

Universitätsklinikum Greifswald, Poliklinik für Zahnerhaltung, Parodontologie und Kinderzahnheilkunde

Greifswald, , Germany

Universitätsklinikum Heidelberg, Poliklinik für Zahnerhaltungskunde, Sektion Parodontologie

Heidelberg, , Germany

University Hospital Muenster, Dept. of Periodontology

Münster, , Germany

Universität Würzburg, Poliklinik für Parodontologie

Würzburg, , Germany

Countries

Germany

References

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Other Identifiers

DFG grant: EH 365/1-1

Identifier Type: -

Identifier Source: secondary_id

ISRCTN : 64254080

Identifier Type: -

Identifier Source: secondary_id

EH 365/1-1

Identifier Type: -

Identifier Source: org_study_id