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

Sponsor

University Hospital Muenster (Other)

Overall Status

Completed

CT.gov ID

NCT00707369

Collaborator

(none)

540

Enrollment

Locations

Arms

Duration (Months)

67.5

Patients Per Site

1.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Periodontitis	Drug: Amoxicillin and Metronidazole Drug: Placebo	Phase 4

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:

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

Study Design

Study Type:

Interventional

Actual Enrollment :

540 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2008

Actual Primary Completion Date :

Dec 1, 2011

Actual Study Completion Date :

Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: Amoxicillin and Metronidazole tablets: Amoxicillin 3H2O 574 mg and 400 mg metronidazole three times daily for 7 days Other Names: Flagyl® 400 Filmtablette Amoxicillin-ratiopharm® 500
Placebo Comparator: control Mechanical debridement plus two placebo tablets three times daily for 7 days. Supportive periodontal therapy in 3-month intervals.	Drug: Placebo Placebo tablets (cellulose powder, lactose monohydrate, magnesium stearate, microcrystalline cellulose): three times daily for 7 days

Arm

Intervention/Treatment

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.

Drug: Amoxicillin and Metronidazole

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

Other Names:

Flagyl® 400 Filmtablette

Amoxicillin-ratiopharm® 500

Placebo Comparator: control

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

Drug: Placebo

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

Outcome Measures

Primary Outcome Measures

Percentage of sites showing attachment loss ≥ 1.3 mm over a 27.5-months period [27.5-months period (six measurements)]

Secondary Outcome Measures

Subjective perception of treatment outcome, attachment gain, pocket probing depths, bleeding on probing, and full mouth plaque score. Microbial colonization dynamic. [over a 27.5-months period]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Medizinische Fakultät der Humboldt Universität Berlin (Charité)	Berlin	Germany	13353
2	Universitätsklinikum Carl Gustav Carus, Zentrum für Zahn-, Mund- und Kieferheilkunde	Dresden	Germany	01307
3	Zentrum der Zahn-, Mund- und Kieferheilkunde (Carolinum), Poliklinik für Parodontologie	Frankfurt	Germany	60590
4	Justus-Liebig-Universität Gießen, Poliklinik für Parodontologie	Giessen	Germany	35392
5	Universitätsklinikum Greifswald, Poliklinik für Zahnerhaltung, Parodontologie und Kinderzahnheilkunde	Greifswald	Germany	17487
6	Universitätsklinikum Heidelberg, Poliklinik für Zahnerhaltungskunde, Sektion Parodontologie	Heidelberg	Germany	69120
7	University Hospital Muenster, Dept. of Periodontology	Muenster	Germany	48149
8	Universität Würzburg, Poliklinik für Parodontologie	Würzburg	Germany	97070