Evaluation of Short-Span Versus Long-Span Amoxicillin Therapy on Peri-Implant Tissue Healing and Antimicrobial Resistance in Healthy Patients

The primary objective of this study is to evaluate whether a short-span antibiotic therapy with **amoxicillin** administered orally is not inferior to a long-span antibiotic prescription in promoting peri-implant tissue healing, specifically by reducing peri-implant bone loss. Additionally, the study aims to assess the potential of short-span therapy in minimizing the risk of developing antimicrobial resistance. This is clinically relevant as it addresses the balance between effective peri-implant healing and the growing concern of antimicrobial resistance, which is a significant issue in dental implant surgery and broader healthcare contexts.

The clinical trial involves a study population comprising **healthy patients** who require a single implant or partial implant-supported rehabilitation in an edentulous area of the posterior mandible or maxilla. The trial includes both male and female participants, with an age range that corresponds to adults. The selection process for the trial population is not specified, and the sponsor has not provided the total number of participants. The study does not focus on a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted. The trial aims to assess the efficacy of short-span antibiotic therapy with amoxicillin in comparison to long-span antibiotic prescriptions in promoting peri-implant tissue healing and reducing the risk of antimicrobial resistance.

The clinical trial is designed to evaluate the efficacy of short-span antibiotic therapy with **amoxicillin** compared to long-span antibiotic prescriptions in promoting peri-implant tissue healing and reducing antimicrobial resistance. This study is a randomized, double-blind, controlled trial involving healthy patients who require a single implant or partial implant-supported rehabilitation in an edentulous area of the posterior mandible or maxilla. The trial is expected to commence on April 2, 2024, and conclude by January 31, 2026, with an estimated duration of participant involvement spanning up to 12 months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on the principal inclusion criteria. Following successful screening, participants will be randomized to receive either short-span or long-span antibiotic therapy. The primary endpoint of the study is the mean bone loss, while secondary endpoints include the incidence of biological and technical complications, implant survival rate, antibiotic sensitivity, peri-implant microbiome and resistome, salivary miRNomics, adverse reactions, and the development of a 3D bone model. Follow-up visits will occur at 1 week before and 2-6 months after implant insertion, with additional assessments at 3, 6, and 12 months to evaluate plaque index, bleeding on probing, and probing depth.

The trial will employ **ZIMOX 1 g compresse**, administered via buccal use, with a maximum daily dose of 3 grams and a total dose not exceeding 18 grams over a maximum treatment period of 6 days. Participants may be withdrawn from the study if they experience significant adverse reactions or fail to comply with the study protocol. The trial is categorized as low-intervention, with the primary objective of demonstrating that short-span antibiotic therapy is not inferior to long-span therapy in terms of peri-implant tissue healing and antimicrobial resistance outcomes.

The clinical trial involves the administration of **ZIMOX 1 g compresse**, which contains the active substance **amoxicillin trihydrate**. This experimental medication is provided in the form of a **tablet** and is intended for **buccal use**. The maximum daily dose is set at 3 grams, with a total maximum dose of 18 grams over the course of the treatment. The treatment period is limited to a maximum of 6 days. The medication is manufactured by Pfizer Italia S.R.L. and is classified under the ATC code J01CA04, indicating its use as an antibiotic. The trial aims to assess the efficacy of short-span antibiotic therapy in dental implant surgery, focusing on peri-implant tissue health and the reduction of antimicrobial resistance.

In addition to the experimental treatment, the study may include non-experimental treatments such as standard-of-care therapy or a comparator treatment, although specific details are not provided in the source data. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial's main objective is to determine if the short-span antibiotic therapy with amoxicillin is not inferior to long-span antibiotic prescriptions in promoting peri-implant tissue healing while minimizing the risk of developing antimicrobial resistance.

Efficacy in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the **mean bone loss** associated with peri-implant tissue healing. This will be measured to determine the effectiveness of short-span antibiotic therapy with amoxicillin compared to long-span antibiotic prescriptions. Secondary endpoints include the incidence of biological and technical complications, implant survival rate (CSR), and antibiotic sensitivity, which will be evaluated one week before and between two to six months after implant insertion. Additionally, the study will assess peri-implant myco-, microbiome, and resistome at similar timepoints, as well as salivary miRNomics one week before and two months after implant insertion. Other secondary endpoints include adverse reactions, the development of a 3D bone model as part of a sub-study, and clinical parameters such as plaque index (PI), bleeding on probing (BOP), and probing depth (PPD) at three, six, and twelve months.