Surgical Access Combined With Systematically Administered Antibiotics in the Treatment of Peri-implantitis

Peri-Implantitis Clinical Trial

Official title:

Clinical and Microbiological Effects of Surgical Access Combined With Systematically Administered Antibiotics in the Treatment of Peri-implantitis: 1-year Randomized Double-blinded Controlled Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05444218
• Other study ID #: 40892620.9.0000.5506
• Secondary ID: 1454_2019
• Status: Recruiting
• Phase: N/A
• Start date: May 1, 2021
• Est. completion date: November 5, 2024

Study information

• Verified date: May 2023
• Source: University of Guarulhos
• Contact: Jamil A Shibli, Professor
• Phone: +55 11 2464-1726
• Email: jshibli[@]ung.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized clinical trial evaluates the clinical and microbiological (microbial complexes and changes in the diversity of the submucosal biofilm) effects of MTZ+AMX as adjuncts to anti-infectious surgical treatment plus Er: YAG in the treatment of peri-implantitis.

Description:

Peri-implantitis is a pathological condition characterized by inflammation of peri-implant connective tissues and progressive peri-implant bone. Recently, the therapeutic protocol using non-surgical debridement associated with the combination of systemic metronidazole (MTZ) and amoxicillin (AMX) has not been shown to be effective in controlling the disease. These unfavorable results may have occurred due to the limitation in the change of the submucosal microbiological profile due to mechanical difficulties in the decontamination of the implant threads. Therefore, this randomized clinical trial (RCT) aimed to evaluate the clinical and microbiological (microbial complexes and changes in the diversity of the submucosal biofilm) effects of MTZ+AMX as adjuncts to anti-infectious surgical treatment plus Er:YAG in the treatment of peri-implantitis. Ninety-four subjects with untreated peri-implantitis are being included and will be randomly assigned to receive (i) open flap debridement plus Er:YAG irradiation alone (control), or (ii) with adjunctive systemically administered MTZ (400 mg) + AMX (500 mg) thrice a day (TID) for 14 days (test). Subjects will be monitored up to 12 months post-treatment. Submucosal biofilm samples from the deepest site of each implant with peri-implantitis will be collected in duplicate per patient: at baseline and at 3, 6 and 12 months post-therapy and analyzed by checkerboard DNA-DNA hybridization for 40 bacterial species, and at baseline, 3 and 12 months post-treatment for 16S rRNA sequencing (Ion Torrent PGM System). The primary outcome variable of this trial will be the difference between treatment groups for the change in CAL from baseline to 12 months. The significance of differences in each group (over the course of the study) will be sought using the Student's-t test; and among groups (at each time point) using either ANOVA /ANCOVA or Kruskal Wallis tests and post-hoc analyses, depending on normality of the data. Fisher's exact test will be used to compare differences in the frequency of gender. Statistical significance will be set at 5%.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 94
• Est. completion date: November 5, 2024
• Est. primary completion date: September 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 18-70 years of age;
• in general good health,
• at least one dental implant in function for at least one year with untreated peri-implantitis defined as: presence of bleeding and/or suppuration on gentle probing, probing depths (PD) = 6mm, and bone levels =3mm apical of the most coronal portion of the intraosseous part of the implant.

Exclusion Criteria:

• subjects with =6 sites with PD =5mm;
• individuals that received periodontal treatment within three months prior to entering the study;
• inability to perform proper supramucosal and supragingival plaque control (e.g., due to improper restoration design or lack of skills);
• poorly adapted implant-supported restoration;
• diabetes;
• pregnancy;
• nursing;
• history of allergies to metronidazole and/or amoxicillin, or any other ingredient of oral care products;
• alcohol or drug abuse;
• any systemic diseases that could affect post-operative healing or that required antibiotic premedication for routine dental therapy;
• long-term use of mouthrinses;
• anti-inflammatory medications;
• any other drug that could interfere with the study outcomes within three months prior to entering the study;
• use of antibiotics within six months prior to entering the study.

Related Conditions & MeSH terms

• Peri-Implantitis

Intervention

Procedure:
• Open flap debridement
After local anesthesia (2% lidocaine with1:100,000 epinephrine), intrasulcular incisions will be performed to create a horizontal flap extending beyond the adjacent teeth and/or implants. Buccal and lingual full-thickness flaps will be dissected, and granulation tissue will be removed to expose the implant threads and bone defect. The flap will be repositioned in its original position and stabilized with interrupted sutures, which will be removed after 10 days.

Other:
• Er: YAG irradiation
An Er:YAG laser (Lite Touch, Light Instruments, Israel) will be used, with an irradiation energy of 20 mJ, frequency of 20 Hz, output power of 0.4 W, and an energy density of 2.76 J/cm2. An 8 mm long sapphire tip will be used in the respective handpiece and not in contact with the titanium surface, with concomitant water spray irrigation, under air 6 and water spray 6, the irradiation angle will be 90 degrees, at a focal distance of 2 mm, with spot size diameter of 1.3 mm

Drug:
• Metronidazole
Metronidazole 400 mg thrice a day for 14 days in the active phase of the periodontal treatment (beginning after open flap debridement).
• Amoxicillin
Amoxicillin 500 mg thrice a day for 14 days in the active phase of the periodontal treatment (beginning after open flap debridement).
• Placebos
Amoxicillin and metronidazole placebos thrice a day for 14 days in the healing phase (beginning after open flap debridement).

Locations

Country	Name	City	State
Brazil	University of Guarulhos	Guarulhos	São Paulo

Sponsors (2)

Lead Sponsor	Collaborator
University of Guarulhos	ITI Foundation

Country where clinical trial is conducted

Brazil, 

References & Publications (16)

Aoki A, Mizutani K, Schwarz F, Sculean A, Yukna RA, Takasaki AA, Romanos GE, Taniguchi Y, Sasaki KM, Zeredo JL, Koshy G, Coluzzi DJ, White JM, Abiko Y, Ishikawa I, Izumi Y. Periodontal and peri-implant wound healing following laser therapy. Periodontol 20 — View Citation

Berglundh T, Armitage G, Araujo MG, Avila-Ortiz G, Blanco J, Camargo PM, Chen S, Cochran D, Derks J, Figuero E, Hammerle CHF, Heitz-Mayfield LJA, Huynh-Ba G, Iacono V, Koo KT, Lambert F, McCauley L, Quirynen M, Renvert S, Salvi GE, Schwarz F, Tarnow D, Tomasi C, Wang HL, Zitzmann N. Peri-implant diseases and conditions: Consensus report of workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol. 2018 Jun;89 Suppl 1:S313-S318. doi: 10.1002/JPER.17-0739. — View Citation

Borges I, Faveri M, Figueiredo LC, Duarte PM, Retamal-Valdes B, Montenegro SCL, Feres M. Different antibiotic protocols in the treatment of severe chronic periodontitis: A 1-year randomized trial. J Clin Periodontol. 2017 Aug;44(8):822-832. doi: 10.1111/j — View Citation

Carcuac O, Derks J, Charalampakis G, Abrahamsson I, Wennstrom J, Berglundh T. Adjunctive Systemic and Local Antimicrobial Therapy in the Surgical Treatment of Peri-implantitis: A Randomized Controlled Clinical Trial. J Dent Res. 2016 Jan;95(1):50-7. doi: — View Citation

Dreyer H, Grischke J, Tiede C, Eberhard J, Schweitzer A, Toikkanen SE, Glockner S, Krause G, Stiesch M. Epidemiology and risk factors of peri-implantitis: A systematic review. J Periodontal Res. 2018 Oct;53(5):657-681. doi: 10.1111/jre.12562. Epub 2018 Jun 7. — View Citation

Faggion CM Jr, Listl S, Fruhauf N, Chang HJ, Tu YK. A systematic review and Bayesian network meta-analysis of randomized clinical trials on non-surgical treatments for peri-implantitis. J Clin Periodontol. 2014 Oct;41(10):1015-25. doi: 10.1111/jcpe.12292. — View Citation

Feres M, Figueiredo LC, Soares GM, Faveri M. Systemic antibiotics in the treatment of periodontitis. Periodontol 2000. 2015 Feb;67(1):131-86. doi: 10.1111/prd.12075. — View Citation

Feres M, Retamal-Valdes B, Fermiano D, Faveri M, Figueiredo LC, Mayer MPA, Lee JJ, Bittinger K, Teles F. Microbiome changes in young periodontitis patients treated with adjunctive metronidazole and amoxicillin. J Periodontol. 2021 Apr;92(4):467-478. doi: — View Citation

Perez-Chaparro PJ, Duarte PM, Shibli JA, Montenegro S, Lacerda Heluy S, Figueiredo LC, Faveri M, Feres M. The Current Weight of Evidence of the Microbiologic Profile Associated With Peri-Implantitis: A Systematic Review. J Periodontol. 2016 Nov;87(11):1295-1304. doi: 10.1902/jop.2016.160184. Epub 2016 Jul 15. — View Citation

Schwarz F, Derks J, Monje A, Wang HL. Peri-implantitis. J Periodontol. 2018 Jun;89 Suppl 1:S267-S290. doi: 10.1002/JPER.16-0350. — View Citation

Shibli JA, Ferrari DS, Siroma RS, Figueiredo LC, Faveri M, Feres M. Microbiological and clinical effects of adjunctive systemic metronidazole and amoxicillin in the non-surgical treatment of peri-implantitis: 1 year follow-up. Braz Oral Res. 2019 Sep 30;3 — View Citation

Shibli JA, Melo L, Ferrari DS, Figueiredo LC, Faveri M, Feres M. Composition of supra- and subgingival biofilm of subjects with healthy and diseased implants. Clin Oral Implants Res. 2008 Oct;19(10):975-82. doi: 10.1111/j.1600-0501.2008.01566.x. — View Citation

Shibli JA. Is Laser the Best Choice for the Treatment of Peri-Implantitis? Photomed Laser Surg. 2018 Nov;36(11):569-570. doi: 10.1089/pho.2018.4521. No abstract available. — View Citation

Swider K, Dominiak M, Grzech-Lesniak K, Matys J. Effect of Different Laser Wavelengths on Periodontopathogens in Peri-Implantitis: A Review of In Vivo Studies. Microorganisms. 2019 Jun 29;7(7):189. doi: 10.3390/microorganisms7070189. — View Citation

Tamashiro NS, Duarte PM, Miranda TS, Maciel SS, Figueiredo LC, Faveri M, Feres M. Amoxicillin Plus Metronidazole Therapy for Patients with Periodontitis and Type 2 Diabetes: A 2-year Randomized Controlled Trial. J Dent Res. 2016 Jul;95(7):829-36. doi: 10. — View Citation

Teughels W, Feres M, Oud V, Martin C, Matesanz P, Herrera D. Adjunctive effect of systemic antimicrobials in periodontitis therapy: A systematic review and meta-analysis. J Clin Periodontol. 2020 Jul;47 Suppl 22:257-281. doi: 10.1111/jcpe.13264. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference between treatment groups for the change in the clinical attachment level (CAL).		12 months.
Secondary	Percentage of patients (and implants) reaching the following clinical endpoint for treatment: PD< 5mm, absence of BOP and no further bone loss.		12 months.
Secondary	Mean plaque index.		Baseline, 3, 6 and 12 months.
Secondary	Mean gingival index.		Baseline, 3, 6 and 12 months.
Secondary	Percentage of sites with bleeding on probing.		Baseline, 3, 6 and 12 months.
Secondary	Percentage of sites with suppuration.		Baseline, 3, 6 and 12 months.
Secondary	Probing depth.		Baseline, 3, 6 and 12 months.
Secondary	Occurrence of headache obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Occurrence of vomiting obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Occurrence of diarrhea obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Occurrence of metallic taste obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Occurrence of nausea obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Occurrence of irritability obtained through a questionnaire of adverse effects.		14 days after taking antibiotic.
Secondary	Proportions of periodontal pathogenic bacterial species.		Baseline, 3, 6 and 12 months.
Secondary	Counts of periodontal pathogenic bacterial species.		Baseline, 3, 6 and 12 months.