Non-Surgical Treatment of Peri-implantitis with Systemic Azithromycin or Placebo (NSTP)

December 4, 2024 updated by: Juan Blanco Carrión, University of Santiago de Compostela

NON-SURGICAL TREATMENT of PERI-IMPLANTITIS with or WITHOUT SYSTEMIC AZITHROMYCIN: a RANDOMIZED CLINICAL TRIAL in HUMANS

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).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

52

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Spain
    • A Coruña
      • Santiago de Compostela, A Coruña, Spain, 15782
        • Department of Surgery and Medical-Surgical Specialties, Teaching and Research Unit in Periodontology. Faculty of Medicine and Dentistry, University of Santiago de Compostela.
        • Contact:
        • Contact:
          • Juan Blanco Carrión

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Azithromycin 500 mg
Systemic antibiotic: Azithromycin 500 mg every 24 hours for 3 days
Drug: Azithromcyin
Immediately after the end of non surgical treatment of periimplantitis and depending on the result of randomization, the exact number of tablets of the placebo to be taken during the following days will be given to the patient.
Placebo Comparator: Placebo
Same shape, size and dosage as test
Other: Placebo
Immediately after the end of non surgical treatment of periimplantitis and depending on the result of randomization, the exact number of tablets of the placebo to be taken during the following days will be given to the patient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in probing depth
Time Frame: From enrollment to the end of treatment at 12 months
The change in probing depth (quantitative dependent variable) at 12 months will be measured in millimeters as the distance from the mucosal margin to the bottom of the peri-implant pocket, using a millimetric CP15 UNC Hu-Friedy probe. The change in probing depth will also be measured at 3 and 6 months.
From enrollment to the end of treatment at 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recession
Time Frame: From enrollment to the end of treatment at 12 months
Distance from the implant shoulder to the margin of the peri-implant mucosa, measured in millimeters using a millimetric CP15 UNC Hu-Friedy probe. If the margin of the peri-implant mucosa is located apically to the implant shoulder, it will be recorded as a positive value (+); conversely, if the margin of the peri-implant mucosa is located coronally to the implant shoulder, it will be recorded as a negative value (-)
From enrollment to the end of treatment at 12 months
Clinical attachment level
Time Frame: From enrollment to the end of treatment at 12 months
Distance from the implant shoulder to the bottom of the peri-implant pocket (probing depth + recession) measured in millimeters using a millimetric CP15 UNC Hu-Friedy probe
From enrollment to the end of treatment at 12 months
Bleeding index
Time Frame: From enrollment to the end of treatment at 12 months
0: absent bleeding / 1: present bleeding
From enrollment to the end of treatment at 12 months
Plaque index
Time Frame: From enrollment to the end of treatment at 12 months
0: absent plaque / 1: present plaque
From enrollment to the end of treatment at 12 months
Width of the keratinized mucosa
Time Frame: From enrollment to the end of treatment at 12 months
From the peri-implant mucosal margin to the mucogingival line measured in millimeters using a millimetric CP15 UNC Hu-Friedy probe
From enrollment to the end of treatment at 12 months
Changes in radiographic bone level
Time Frame: From enrollment to the end of treatment at 12 months
Distance from the implant shoulder to the apical extent of the bone defect in mesial, distal, and total (calculated as the average of mesial and distal distances) of each implant on standardized periapical radiographs following the long cone paralleling technique with individualized positioning devices.
From enrollment to the end of treatment at 12 months
Change in bacterial load
Time Frame: From enrollment to the end of treatment at 12 months
The levels of the following pathogens will be determined: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Parvimonas micra, Fusobacterium nucleatum, Campylobacter rectus, Eikenella corrodens, Candida albicans and the total bacterial count.
From enrollment to the end of treatment at 12 months
Implant survival
Time Frame: From enrollment to the end of treatment at 12 months
Maintenance of each implant's function included in the study
From enrollment to the end of treatment at 12 months
Endothelial function
Time Frame: From enrollment to the end of treatment at 12 months
Measured by endothelium-dependent vasodilation in the brachial artery using a vascular ultrasound
From enrollment to the end of treatment at 12 months
Subclinical atherosclerosis
Time Frame: From enrollment to the end of treatment at 12 months
Measured by the intima-media thickness of the carotid artery using a vascular ultrasound
From enrollment to the end of treatment at 12 months
Treatment success
Time Frame: From enrollment to the end of treatment at 12 months
Treatment success will be established as achieving a probing depth ≤5 mm, without bleeding in more than one point, and without suppuration, in each implant included in the study.
From enrollment to the end of treatment at 12 months
Concentration of inflammatory cytokines biomarkers
Time Frame: From enrollment to the end of treatment at 12 months
The predetermined biomarkers to be analyzed include a multiplex inflammatory panel (IL-1β, IL-12p70, IFN-γ, IL-6, IL-10, IL-8, TNF-α), measured in pg/mL
From enrollment to the end of treatment at 12 months
Concentration of endothelial activation/injury markers
Time Frame: From enrollment to the end of treatment at 12 months
Endothelial activation/injury markers (E-selectin, P-selectin, thrombomodulin, ICAM-1, ICAM-3, VCAM-1), measured in ng/mL
From enrollment to the end of treatment at 12 months
Concentration of serum C-reactive protein
Time Frame: From enrollment to the end of treatment at 12 months
C-reactive protein (CRP), measured in mg/L using Meso Scale assays (pro-inflammatory 7-PLEX, Vascular Injury Panel I, and V-PLEX Panel II)
From enrollment to the end of treatment at 12 months
Concentration of serum amyloid A
Time Frame: From enrollment to the end of treatment at 12 months
Serum amyloid A (SAA), measured in µg/mL using Meso Scale assays (pro-inflammatory 7-PLEX, Vascular Injury Panel I, and V-PLEX Panel II)
From enrollment to the end of treatment at 12 months
Concentration of circulating blood cells
Time Frame: From enrollment to the end of treatment at 12 months
Circulating blood cells will be measured in 10³/µL
From enrollment to the end of treatment at 12 months
Concentration of high-sensitivity CRP
Time Frame: From enrollment to the end of treatment at 12 months
High-sensitivity CRP (hs-CRP) will be assessed using ELISA, in mg/L
From enrollment to the end of treatment at 12 months
Rate of lipid fractions
Time Frame: From enrollment to the end of treatment at 12 months
Lipid fractions (triglycerides, total cholesterol, HDL, LDL) will be assessed in mg/dL using standard biochemical methods
From enrollment to the end of treatment at 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Santiago de Compostela

Investigators

  • Principal Investigator: Juan Blanco Carrión, Universidade de Santiago de Compostela

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 10, 2025

Primary Completion (Estimated)

January 10, 2026

Study Completion (Estimated)

January 10, 2027

Study Registration Dates

First Submitted

November 11, 2024

First Submitted That Met QC Criteria

December 2, 2024

First Posted (Actual)

December 4, 2024

Study Record Updates

Last Update Posted (Estimated)

December 10, 2024

Last Update Submitted That Met QC Criteria

December 4, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • USC77/2024
  • Self founding (Other Identifier: Universidade de Santiago de Compostela)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Peri-implantitis

Clinical Trials on Azithromcyin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kyrgyzstan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe