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

NCT00707369 | Completed Phase 4 DMC

• 3 other identifiers: EH 365/1-1DFG grant: EH 365/1-1ISRCTN : 64254080
• Study Type: interventional
• Target: 540
• Locations: 1 country
• Sites: 8

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.

Conditions

Periodontitis

Keywords

Periodontitis; Mechanical Debridement; Antibiotics; Attachment loss; Randomized controlled trial

Outcome Measures

Primary Outcomes (1)

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

  27.5-months period (six measurements)

Secondary Outcomes (1)

• 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

Study Arms (2)

test

EXPERIMENTAL

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

control

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Amoxicillin and Metronidazole DRUG

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

Also known as: Flagyl® 400 Filmtablette, Amoxicillin-ratiopharm® 500

test

Placebo DRUG

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

control

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital Muenster: lead

Study Sites (8)

Medizinische Fakultät der Humboldt Universität Berlin (Charité)

Berlin, 13353, Germany

Location

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

Dresden, 01307, Germany

Location

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

Frankfurt, 60590, Germany

Location

Justus-Liebig-Universität Gießen, Poliklinik für Parodontologie

Giessen, 35392, Germany

Location

Universitätsklinikum Greifswald, Poliklinik für Zahnerhaltung, Parodontologie und Kinderzahnheilkunde

Greifswald, 17487, Germany

Location

Universitätsklinikum Heidelberg, Poliklinik für Zahnerhaltungskunde, Sektion Parodontologie

Heidelberg, 69120, Germany

Location

University Hospital Muenster, Dept. of Periodontology

Münster, 48149, Germany

Location

Universität Würzburg, Poliklinik für Parodontologie

Würzburg, 97070, Germany

Location

Related Publications (7)

• 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.

  PMID: 35806269 DERIVED

• 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.

  PMID: 33197289 DERIVED

• 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.

  PMID: 32248552 DERIVED

• 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.

  PMID: 30825384 DERIVED

• 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.

  PMID: 30326764 DERIVED

• 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.

  PMID: 27393928 DERIVED

• 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.

  PMID: 26250060 DERIVED

MeSH Terms

Conditions

Periodontitis

Interventions

Amoxicillin; Metronidazole

Condition Hierarchy (Ancestors)

Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Benjamin - Ehmke, PhD

  University Hospital Muenster, Dept. of Periodontology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med. dent.

Study Record Dates

• First Submitted: June 24, 2008
• First Posted: June 30, 2008
• Study Start: October 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: January 1, 2012
• Last Updated: March 3, 2015

Record last verified: 2015-03

Locations

DE (8)