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

Sponsor:	University Hospital Muenster
Information provided by:	University Hospital Muenster
ClinicalTrials.gov Identifier:	NCT00707369

Purpose

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	Intervention	Phase
Periodontitis	Drug: Amoxicillin and Metronidazole Drug: Placebo	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Adjunctive Antimicrobial Therapy of Periodontitis: Long-Term Effects on Disease Progression and Oral Microbiological Colonization

Resource links provided by NLM:

MedlinePlus related topics: Antibiotics

Drug Information available for: Amoxicillin Amoxicillin sodium Amoxicillin trihydrate Metronidazole hydrochloride Metronidazole phosphate Metronidazole

U.S. FDA Resources

Further study details as provided by University Hospital Muenster:

Primary Outcome Measures:

Percentage of sites showing attachment loss ≥ 1.3 mm over a 27.5-months period [ Time Frame: 27.5-months period (six measurements) ] [ Designated as safety issue: No ]

Secondary Outcome 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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	500
Study Start Date:	October 2008
Estimated Study Completion Date:	January 2012
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00707369

Locations

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

Sponsors and Collaborators

University Hospital Muenster

Investigators

Principal Investigator:

Benjamin - Ehmke, PhD

University Hospital Muenster, Dept. of Periodontology

More Information

Additional Information:

study web page This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Prof. Dr. med. dent. Benjamin Ehmke, Universitätsklinikum Münster, Poliklinik für Parodontologie,
ClinicalTrials.gov Identifier:	NCT00707369 History of Changes
Other Study ID Numbers:	EH 365/1-1, DFG grant: EH 365/1-1, ISRCTN : 64254080
Study First Received:	June 24, 2008
Last Updated:	August 11, 2011
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Muenster:

Periodontitis
Mechanical Debridement
Antibiotics
Attachment loss
Randomized controlled trial

Additional relevant MeSH terms:

Periodontitis
Disease Progression
Periodontal Diseases
Mouth Diseases
Stomatognathic Diseases
Disease Attributes
Pathologic Processes
Amoxicillin
Anti-Infective Agents

Metronidazole
Anti-Bacterial Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on February 12, 2012