The Effect of Different Antibiotic Protocols on Peri-implant Tissue Health

The Effect of Different Antibiotic Protocols for Dental Implant Surgery on Peri-implant Tissue Health and on Oral Microbiome and Resistome

The aim of the present project (non-inferiority trial) is to evaluate the effect of different antibiotic strategies (long-span vs. short-span) for implant surgery on peri-implant tissue health, oral microbiome (included resistome) and salivary MiRNomics in healthy patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Antibiotic
• Intervention / Treatment: Drug: Amoxicillin Long; Drug: Amoxicillin Short

Detailed Description

A total of 80 patients will be included and randomly divided in two groups:

1. Long-span prescription: 1 g Amoxicillin every 8 h starting 1 day before surgery and for 5 days after surgery
2. Short-span prescription: 2 g Amoxicillin 1 h before surgery Before surgery, patients will undergo an antibiotic sensitivity test (AST), and non-invasive samples will be taken to analyse oral microbiome including resistome. Saliva samples will be also taken for miRNomics analysis. Patients will be rehabilitated with single implants or partial implant-supported fixed prostheses. The day of surgery, samples of peripheral blood will be taken and peripheral blood mononuclear cells (PBMCs) isolated from the first 30 patients in order to implement a micro-fluidic bioreactor replicating the bone healing process of each patient. 3D bone models will be developed that are suitable for drug screening.

At 2 and 6 months post-treatment, AST test and oral microbiome and resistome analysis will be performed again. 2 months after treatment, a new saliva sample of the patients will be also taken, analysed and compared using MiRnomics technology with the preoperative one with the further aim of identifying reliable biomarkers of mucositis and perimplantitis. During the 12-month follow-up implant survival rate, marginal bone loss (MBL), biologic and technical complication rate and peri-implant health parameters (including plaque index, probing depth and bleeding on probing) will be evaluated.

Parametric or non-parametric comparative tests, as appropriate, will be performed to detect differences between the groups in the various outcome variables. The effect of patient-related and implant-related predictive factors on the various outcomes will be evaluated using multilevel logistic regression analysis. Metadata will be analyzed also with 4th generation Artificial Neural Networks (ANNs) (machine learning) using unsupervised and supervised systems.

Expected results: The present project is expected to clarify if the short-span antibiotic therapy is not inferior to the long-span one in healthy patients undergoing implant surgery. The outcomes will contribute to the development of effective clinical guidelines that will help to tackle the issue of antimicrobial resistance. In addition, the development and validation of a 3D bone model to be used for drug screening is expected, that might overcome limitations of currently available 2D bone models and animal studies. A further expected result is the identification of biomarkers for diagnosis and prognosis in implant dentistry, through salivary miRNomics that might lead to the development of a non-invasive liquid biopsy.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Maria Menini; Phone Number: 3396598789‬; Email: maria.menini@unige.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Healthy volunteers requiring one single implant or partial implant-supported rehabilitation in an edentulous area of the posterior mandible or maxilla

Exclusion Criteria:

• Patients unable to commit to follow-up
• General contraindications to implant surgery
• Immuno-suppressed/immune-compromised patients
• Patients irradiated in the head and/or neck
• Uncontrolled diabetes
• Pregnancy, childbearing potential, breastfeeding
• Smoking habit
• Untreated periodontal disease (Caton et al, J Clin Periodontol 2018)
• Poor oral hygiene and motivation (plaque index > 20%)
• Addiction to alcohol or drugs
• Psychiatric problems and/or unrealistic expectations
• Patients with an acute infection (abscess) or suppuration in the site intended for implant placement
• Patients treated or under treatment with intravenous amino-bisphosphonates
• Patients referred only for implant placement if the follow-up cannot be done at the treatment center
• Patients participating in other studies, if the present protocol could not be fully adhered to
• Patients with allergy/hypersensitivity to penicillin or drug excipients
• Patients recently treated with antibiotics for other indications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Long-span therapy; 1 g Amoxicillin every 8 h starting 1 day before surgery and for 5 days after surgery	Drug: Amoxicillin Long; Long span
Experimental: Short-span therapy; 2 g Amoxicillin 1 h before surgery	Drug: Amoxicillin Short; Short Span

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean peri-implant bone loss	bone loss	at 6 and 12 months after prosthesis delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of biological and technical complications at the implant site	complications	12 months
implant survival rate	CSR	12 months
Antibiotic sensitivity	sensitivity	1 week before and 2 months and 6 months after implant insertion
Peri-implant myco-, microbiome and resistome	resistome	1 week before and 2 months and 6 months after implant insertion
Salivary miRNomics	miRNomics	1 week before and 2 months after implant insertion
Adverse reactions	reaction	during the entire follow-up period
Development of a 3D bone model	3D bone model	1 year
Plaque index (PI)	measured on 6 surfaces each tooth - percentage value	3, 6 and 12 months after prosthesis delivery
Bleeding on probing (BOP)	measured on 6 surfaces each tooth - percentage value	3, 6 and 12 months after prosthesis delivery
Peri-implant pocket probing depth (PPD)	measured on 6 surfaces each tooth - percentage value	3, 6 and 12 months after prosthesis delivery

Collaborators and Investigators

• Sponsor: Universita degli Studi di Genova

Study record dates

Study Major Dates

• Study Start (Estimated): May 3, 2024
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: April 17, 2024
• First Submitted That Met QC Criteria: April 17, 2024
• First Posted (Actual): April 22, 2024

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Amoxicillin
• Other Study ID Numbers: antibiotic-resistence

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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