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

Primary Purpose

Periodontitis

Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Amoxicillin and Metronidazole
Placebo
Sponsored by
University Hospital Muenster
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Periodontitis focused on measuring Periodontitis, Mechanical Debridement, Antibiotics, Attachment loss, Randomized controlled trial

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Medizinische Fakultät der Humboldt Universität Berlin (Charité)
  • Universitätsklinikum Carl Gustav Carus, Zentrum für Zahn-, Mund- und Kieferheilkunde
  • Zentrum der Zahn-, Mund- und Kieferheilkunde (Carolinum), Poliklinik für Parodontologie
  • Justus-Liebig-Universität Gießen, Poliklinik für Parodontologie
  • Universitätsklinikum Greifswald, Poliklinik für Zahnerhaltung, Parodontologie und Kinderzahnheilkunde
  • Universitätsklinikum Heidelberg, Poliklinik für Zahnerhaltungskunde, Sektion Parodontologie
  • University Hospital Muenster, Dept. of Periodontology
  • Universität Würzburg, Poliklinik für Parodontologie

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

test

control

Arm Description

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

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

Outcomes

Primary Outcome Measures

Percentage of sites showing attachment loss ≥ 1.3 mm over a 27.5-months period

Secondary Outcome Measures

Subjective perception of treatment outcome, attachment gain, pocket probing depths, bleeding on probing, and full mouth plaque score. Microbial colonization dynamic.

Full Information

First Posted
June 24, 2008
Last Updated
March 2, 2015
Sponsor
University Hospital Muenster
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1. Study Identification

Unique Protocol Identification Number
NCT00707369
Brief Title
Adjunctive Antimicrobial Therapy of Periodontitis: Long-Term Effects on Disease Progression and Oral Microbiological Colonization
Acronym
ABPARO-Studie
Official Title
Adjunctive Antimicrobial Therapy of Periodontitis: Long-Term Effects on Disease Progression and Oral Microbiological Colonization
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital Muenster

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Periodontitis
Keywords
Periodontitis, Mechanical Debridement, Antibiotics, Attachment loss, Randomized controlled trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
540 (Actual)

8. Arms, Groups, and Interventions

Arm Title
test
Arm Type
Experimental
Arm Description
Mechanical debridement plus 500 mg amoxicillin and 400 mg metronidazole three times daily for 7 days. Supportive periodontal therapy in 3-month intervals.
Arm Title
control
Arm Type
Placebo Comparator
Arm Description
Mechanical debridement plus two placebo tablets three times daily for 7 days. Supportive periodontal therapy in 3-month intervals.
Intervention Type
Drug
Intervention Name(s)
Amoxicillin and Metronidazole
Other Intervention Name(s)
Flagyl® 400 Filmtablette, Amoxicillin-ratiopharm® 500
Intervention Description
tablets: Amoxicillin 3H2O 574 mg and 400 mg metronidazole three times daily for 7 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets (cellulose powder, lactose monohydrate, magnesium stearate, microcrystalline cellulose): three times daily for 7 days
Primary Outcome Measure Information:
Title
Percentage of sites showing attachment loss ≥ 1.3 mm over a 27.5-months period
Time Frame
27.5-months period (six measurements)
Secondary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benjamin - Ehmke, PhD
Organizational Affiliation
University Hospital Muenster, Dept. of Periodontology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medizinische Fakultät der Humboldt Universität Berlin (Charité)
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus, Zentrum für Zahn-, Mund- und Kieferheilkunde
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Zentrum der Zahn-, Mund- und Kieferheilkunde (Carolinum), Poliklinik für Parodontologie
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Justus-Liebig-Universität Gießen, Poliklinik für Parodontologie
City
Giessen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Universitätsklinikum Greifswald, Poliklinik für Zahnerhaltung, Parodontologie und Kinderzahnheilkunde
City
Greifswald
ZIP/Postal Code
17487
Country
Germany
Facility Name
Universitätsklinikum Heidelberg, Poliklinik für Zahnerhaltungskunde, Sektion Parodontologie
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
University Hospital Muenster, Dept. of Periodontology
City
Muenster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Universität Würzburg, Poliklinik für Parodontologie
City
Würzburg
ZIP/Postal Code
97070
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
35806269
Citation
Walther KA, Gonzales JR, Groger S, Ehmke B, Kaner D, Lorenz K, Eickholz P, Kocher T, Kim TS, Schlagenhauf U, Koch R, Meyle J. The Role of Polymorphisms at the Interleukin-1, Interleukin-4, GATA-3 and Cyclooxygenase-2 Genes in Non-Surgical Periodontal Therapy. Int J Mol Sci. 2022 Jun 30;23(13):7266. doi: 10.3390/ijms23137266.
Results Reference
derived
PubMed Identifier
33197289
Citation
Khattri S, Kumbargere Nagraj S, Arora A, Eachempati P, Kusum CK, Bhat KG, Johnson TM, Lodi G. Adjunctive systemic antimicrobials for the non-surgical treatment of periodontitis. Cochrane Database Syst Rev. 2020 Nov 16;11(11):CD012568. doi: 10.1002/14651858.CD012568.pub2.
Results Reference
derived
PubMed Identifier
32248552
Citation
Matern J, Koch R, Petersmann A, Kocher T, Eickholz P, Lorenz K, Kim TS, Meyle J, Kaner D, Schlagenhauf U, Gravemeier M, Harks I, Ehmke B. Effect of periodontal therapy on adipokine biomarkers in overweight. J Clin Periodontol. 2020 Jul;47(7):842-850. doi: 10.1111/jcpe.13288. Epub 2020 May 11.
Results Reference
derived
PubMed Identifier
30825384
Citation
Eickholz P, Koch R, Kocher T, Hoffmann T, Kim TS, Meyle J, Kaner D, Schlagenhauf U, Harmsen D, Harks I, Ehmke B. Clinical benefits of systemic amoxicillin/metronidazole may depend on periodontitis severity and patients' age: An exploratory sub-analysis of the ABPARO trial. J Clin Periodontol. 2019 Apr;46(4):491-501. doi: 10.1111/jcpe.13096. Epub 2019 Apr 12.
Results Reference
derived
PubMed Identifier
30326764
Citation
Kocher T, Holtfreter B, Petersmann A, Eickholz P, Hoffmann T, Kaner D, Kim TS, Meyle J, Schlagenhauf U, Doering S, Gravemeier M, Prior K, Rathmann W, Harks I, Ehmke B, Koch R. Effect of Periodontal Treatment on HbA1c among Patients with Prediabetes. J Dent Res. 2019 Feb;98(2):171-179. doi: 10.1177/0022034518804185. Epub 2018 Oct 16.
Results Reference
derived
PubMed Identifier
27393928
Citation
Eickholz P, Nickles K, Koch R, Harks I, Hoffmann T, Kim TS, Kocher T, Meyle J, Kaner D, Schlagenhauf U, Doering S, Gravemeier M, Ehmke B. Is furcation involvement affected by adjunctive systemic amoxicillin plus metronidazole? A clinical trials exploratory subanalysis. J Clin Periodontol. 2016 Oct;43(10):839-48. doi: 10.1111/jcpe.12594. Epub 2016 Aug 10.
Results Reference
derived
PubMed Identifier
26250060
Citation
Harks I, Koch R, Eickholz P, Hoffmann T, Kim TS, Kocher T, Meyle J, Kaner D, Schlagenhauf U, Doering S, Holtfreter B, Gravemeier M, Harmsen D, Ehmke B. Is progression of periodontitis relevantly influenced by systemic antibiotics? A clinical randomized trial. J Clin Periodontol. 2015 Sep;42(9):832-842. doi: 10.1111/jcpe.12441. Epub 2015 Sep 22.
Results Reference
derived

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

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