Clinical trial NCT06715150: Non-Surgical Treatment of Peri-implantitis with Systemic Azithromycin or Placebo
Official title: NON-SURGICAL TREATMENT of PERI-IMPLANTITIS with or WITHOUT SYSTEMIC AZITHROMYCIN: a RANDOMIZED CLINICAL TRIAL in HUMANS
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Peri-implantitis
Keywords: Non-surgical treatment
Azithromycin
Systemic antibiotic
Lead sponsor: University of Santiago de Compostela
Sponsor class: OTHER
First posted: 2024-12-04
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the change in probing depth in patients with peri-implantitis, assessing the influence of systemic antibiotic (azithromycin) adjunctive to non-surgical treatment at 12 months. The secondary objective is to assess clinical, radiographic, microbiological, and systemic changes at 3, 6, and 12 months.

This study is designed as a placebo-controlled, randomized, triple-blind clinical trial in subjects diagnosed with peri-implantitis.

The treatment will consist of debridement of the implant surface and curettage of the pocket epithelium. The control group will receive placebo (1 placebo tablet per day for 3 days), and the test group will receive systemic azithromycin 500 mg per day for 3 days (1 tablet of 500 mg azithromycin per day for 3 days).

Detailed description: Peri-implantitis is defined as the pathological alteration associated with plaque that occurs in the tissues surrounding dental implants, characterized by inflammation of the peri-implant mucosa and subsequent progressive loss of supporting bone. Bacterial colonization of the implant surface in a susceptible subject is considered the primary etiological factor of this pathology. Case series and clinical trials have demonstrated an additional benefit when using systemic antibiotics such as ornidazole or metronidazole after non-surgical treatment of peri-implantitis.

The rationale for conducting this clinical trial lies in the lack of randomized studies that have tested the non-surgical treatment of peri-implantitis with shorter antibiotic regimens and their potential impact on systemic health.

The primary objective of this randomized clinical trial is to evaluate the change in probing depth at 12 months in patients with peri-implantitis, assessing the influence of systemic antibiotic (azithromycin) as an adjunct to the non-surgical treatment of peri-implantitis.

The secondary objective is to assess clinical, radiographic, and microbiological changes at 3, 6, and 12 months. Additionally, systemic biomarkers, complete blood count, glycosylated hemoglobin and creatinine will be evaluated at day 7, and 3, 6, and 12 months. Endothelial function (endothelium-dependent vasodilation measured in the brachial artery) and subclinical atherosclerosis (measurement of carotid artery intima-media thickness) will be evaluated at 12 months.

Design: This research is designed as a 1-year randomized controlled trial (RCT), with 2 parallel groups, triple-blind, and placebo-controlled.

Population: Patients who come to the Periodontology Department, Faculty of Dentistry, University of Santiago de Compostela with dental implants presenting pathology.

Treatment Groups: Study group: patients treated by non-surgical treatment in conjunction with systemic azithromycin. Control group: patients treated by non-surgical treatment in conjunction with a placebo. Subjects will be randomly assigned to one of the two treatment groups.

Randomization: A balanced randomization by blocks will be performed to avoid imbalances between the two treatment groups. The randomization outcome will be stored in envelopes along with the antibiotic or placebo containers that will be delivered on the day of the non-surgical treatment.

Treatment: After the diagnosis of peri-implantitis, patients were instructed in oral hygiene and motivation was reinforced. After that, one session of nonsurgical treatment consisting of supra- and submucosal mechanical debridement using ultrasound with a metal periodontal tip was performed with concomitant irrigation of chlorhexidine of 0.12%. The tip removed granulation tissue and also touched the implant surface. After that, a steel curette Columbia 4R/4L was used to remove granulation tissue and minor mucosa curettage. If oral hygiene was not allowed by prosthetic design, a contour correction was made. Immediately after treatment, patients were prescribed to apply a chlorhexidine gel in the area 2 times a day for 2 weeks and depending on the result of randomization, the exact number of antibiotic or placebo tablets to be taken by the patient in the following days will be provided.

Eligibility criteria: Inclusion Criteria:

* older than 18 years;
* absence of systemic pathology contraindicating treatment;
* presence of at least 1 implant diagnosed with peri-implantitis: presence of bleeding on probing, probing depth ≥6 mm, and radiographic bone level ≥3 mm apical to the most coronal portion of the intraosseous part of the implant;
* absence of implant mobility;
* patients without periodontitis or with treated periodontitis;
* patients who understand the treatment and are willing to comply with it by providing written informed consent.

Exclusion Criteria:

* smokers ≥10 cigarettes/day;
* diabetic patients (HbA1c level ≥6,5%);
* pregnant or breastfeeding women;
* use of antibiotics, corticosteroids, and/or immunosuppressive treatment in the 3 months prior to the start of the study;
* allergy to azithromycin;
* patients with a history of bisphosphonate treatment;
* chronic consumption of non-steroidal anti-inflammatory drugs;
* bone loss exceeding the apex of the implant;
* prosthesis that does not allow access to peri-implantitis treatment

Primary outcomes:
measure: Change in probing depth
timeFrame: From enrollment to the end of treatment at 12 months
Secondary outcomes:
measure: Recession
timeFrame: From enrollment to the end of treatment at 12 months
measure: Clinical attachment level
timeFrame: From enrollment to the end of treatment at 12 months
measure: Bleeding index
timeFrame: From enrollment to the end of treatment at 12 months
measure: Plaque index
timeFrame: From enrollment to the end of treatment at 12 months
measure: Width of the keratinized mucosa
timeFrame: From enrollment to the end of treatment at 12 months
measure: Changes in radiographic bone level
timeFrame: From enrollment to the end of treatment at 12 months
measure: Change in bacterial load
timeFrame: From enrollment to the end of treatment at 12 months
measure: Implant survival
timeFrame: From enrollment to the end of treatment at 12 months
measure: Endothelial function
timeFrame: From enrollment to the end of treatment at 12 months
measure: Subclinical atherosclerosis
timeFrame: From enrollment to the end of treatment at 12 months
measure: Concentration of inflammatory cytokines biomarkers
timeFrame: From enrollment to the end of treatment at 12 months
measure: Concentration of endothelial activation/injury markers
timeFrame: From enrollment to the end of treatment at 12 months
measure: Concentration of serum C-reactive protein
timeFrame: From enrollment to the end of treatment at 12 months
measure: Concentration of serum amyloid A
timeFrame: From enrollment to the end of treatment at 12 months
measure: Concentration of circulating blood cells
timeFrame: From enrollment to the end of treatment at 12 months
measure: Concentration of high-sensitivity CRP
timeFrame: From enrollment to the end of treatment at 12 months
measure: Rate of lipid fractions
timeFrame: From enrollment to the end of treatment at 12 months
measure: Treatment success
timeFrame: From enrollment to the end of treatment at 12 months
Other outcomes:
Locations:
city: Santiago de Compostela
country: Spain
facility: Department of Surgery and Medical-Surgical Specialties, Teaching and Research Unit in Periodontology. Faculty of Medicine and Dentistry, University of Santiago de Compostela.
state: A Coruña
Study officials:
affiliation: Universidade de Santiago de Compostela
name: Juan Blanco Carrión
role: PRINCIPAL_INVESTIGATOR
References:
citation: Orlandi M, Pranno N, Patel V, Papi P, Di Murro B, Pompa G, Polimeni A, Letizia C, Suvan J, D'Aiuto F. Peri-implant diseases and systemic inflammation: A preliminary analysis from a cross-sectional survey of patients with hypertension. J Periodontol. 2024 Jun;95(6):525-534. doi: 10.1002/JPER.21-0338. Epub 2024 May 14.
citation: Blanco C, Linares A, Dopico J, Pico A, Sobrino T, Leira Y, Blanco J. Peri-implantitis, systemic inflammation, and dyslipidemia: a cross-sectional biochemical study. J Periodontal Implant Sci. 2021 Oct;51(5):342-351. doi: 10.5051/jpis.2100920046.
citation: Linares A, Pico A, Blanco C, Blanco J. Adjunctive Systemic Metronidazole to Nonsurgical Therapy of Peri-implantitis with Intrabony Defects: A Retrospective Case Series Study. Int J Oral Maxillofac Implants. 2019 Sep/Oct;34(5):1237-1245. doi: 10.11607/jomi.7343.
citation: Renvert S, Lessem J, Dahlen G, Renvert H, Lindahl C. Mechanical and repeated antimicrobial therapy using a local drug delivery system in the treatment of peri-implantitis: a randomized clinical trial. J Periodontol. 2008 May;79(5):836-44. doi: 10.1902/jop.2008.070347.
citation: Linares A, Sanz-Sanchez I, Dopico J, Molina A, Blanco J, Montero E. Efficacy of adjunctive measures in the non-surgical treatment of peri-implantitis: A systematic review. J Clin Periodontol. 2023 Jun;50 Suppl 26:224-243. doi: 10.1111/jcpe.13821. Epub 2023 May 4.
citation: Estefania-Fresco R, Garcia-de-la-Fuente AM, Egana-Fernandez-Valderrama A, Bravo M, Aguirre-Zorzano LA. One-year results of a nonsurgical treatment protocol for peri-implantitis. A retrospective case series. Clin Oral Implants Res. 2019 Jul;30(7):702-712. doi: 10.1111/clr.13456. Epub 2019 Jun 1.
citation: Blanco C, Pico A, Dopico J, Gandara P, Blanco J, Linares A. Adjunctive benefits of systemic metronidazole on non-surgical treatment of peri-implantitis. A randomized placebo-controlled clinical trial. J Clin Periodontol. 2022 Jan;49(1):15-27. doi: 10.1111/jcpe.13564. Epub 2021 Oct 28.