Evaluation of Anhydrous Benzoyl Peroxide and Ethanol-Povidone Iodine Solution for Reducing Cutibacterium acnes in Male Shoulder Arthroplasty

The primary objective of this study is to evaluate the **efficacy** of a 5% benzoyl peroxide topical treatment applied daily for five days prior to surgery on reducing the **bacterial load** of **Cutibacterium acnes** in the dermis during shoulder arthroplasty in male patients. This is clinically relevant as reducing bacterial load can potentially decrease the risk of postoperative infections, which are a significant concern in prosthetic surgeries.

Secondary objectives include:

• Evaluating the effectiveness of 5% benzoyl peroxide on the bacterial load of **Cutibacterium acnes** at the skin, fat, and capsular levels, and the incidence of infections within two years post-surgery.
• Assessing the efficacy of 5% alcoholic iodine povidone as an antiseptic on the cutaneous bacterial load of **Cutibacterium acnes**.
• Characterizing the different strains of **Cutibacterium acnes** at the phylotypic and genotypic levels.
• Evaluating the skin tolerance of the 5% benzoyl peroxide gel application.

The clinical trial focuses on evaluating the efficacy of a 5% benzoyl peroxide topical treatment in reducing **Cutibacterium acnes** bacterial load in the dermis of the surgical skin incision area for shoulder arthroplasty in men. The study population consists exclusively of **male** patients who are adults, with an age range corresponding to categories 3 and 4, which typically includes individuals from young adulthood to middle age. Participants are required to have no history of surgical intervention on the operated shoulder and are managed for glenohumeral arthroplasty due to primary osteoarthritis or secondary conditions such as necrosis, massive rotator cuff tear, or old fracture. All participants must be affiliated with a social security system and have provided informed and written consent. The trial does not include female subjects or vulnerable populations. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the efficacy of a **5% benzoyl peroxide** topical treatment in reducing **Cutibacterium acnes** bacterial load in the dermis of the surgical skin incision area in male patients undergoing shoulder arthroplasty. This is a randomized, double-blind, controlled trial with an estimated duration from June 19, 2020, to June 19, 2029. Participants will be randomly assigned to either the interventional group, receiving the benzoyl peroxide treatment, or the control group. The primary endpoint is the number of patients in each group with a positive **Cutibacterium acnes** sample at the dermis. Secondary endpoints include the average number of positive intraoperative samples, incidence of infections up to two years post-implantation, and evaluation of skin tolerance.

The trial involves several study visits. The inclusion visit, or screening visit, will confirm eligibility based on criteria such as being an adult male without prior surgical intervention on the operated shoulder and having provided informed consent. Participants will then undergo a baseline skin sample collection to assess initial bacterial load. The treatment phase involves daily application of the topical treatment for five days preceding the surgical procedure. Follow-up visits will occur post-surgery to collect additional skin samples and assess the incidence of infections and skin tolerance. The end-of-study visit will evaluate long-term outcomes, including infection rates and any adverse effects.

Participant involvement is expected to last from the initial screening through the end-of-study visit, with the primary treatment phase lasting five days. Conditions that may lead to early termination from the study include withdrawal of consent, non-compliance with study procedures, or adverse reactions to the treatment. The trial aims to provide valuable insights into optimizing skin preparation to reduce bacterial colonization during shoulder arthroplasty.

The clinical trial involves the use of **CUTACNYL 5 POUR CENT**, a topical gel containing **anhydrous benzoyl peroxide** as the active ingredient. This pharmaceutical form is a gel intended for **cutaneous use**. The treatment is administered daily for a period of five days prior to the surgical procedure. The maximum daily dose is one unit, with a total maximum dose of five units over the treatment period. The gel is manufactured by Galderma International and is not a pediatric formulation. The primary objective of this treatment is to reduce the bacterial load of **Cutibacterium acnes** in the dermis of the surgical incision area during shoulder arthroplasty in male patients.

In addition to the experimental treatment, the study utilizes **BETADINE ALCOOLIQUE 5%**, a cutaneous solution provided in a unidose container. This solution contains **ethanol (96 per cent)** and **povidone, iodinated** as active substances. The solution is also intended for **cutaneous use** and is applied once, with a maximum treatment period of one day. The product is manufactured by Meda Pharma SAS and is not formulated for pediatric use. The solution serves as an auxiliary treatment in the trial, complementing the primary experimental medication.

The efficacy of the clinical trial will be assessed by evaluating the reduction of **Cutibacterium acnes** bacterial load in the dermis of the surgical skin incision area. The primary endpoint is the number of patients in each group (interventional: benzoyl peroxide 5% for 5 days or control) with a positive **Cutibacterium acnes** sample at the dermis. Secondary endpoints include the average number of positive intraoperative **Cutibacterium acnes** samples taken at the cutaneous level before and after cutaneous antisepsis of the operating area, the incidence of **Cutibacterium acnes** shoulder prosthesis infections up to 2 years post-implantation, and the determination of phylotype and molecular typing of **Cutibacterium acnes** strains.

Measurements will be conducted using molecular biology techniques such as Multi-Locus Sequence Typing and Single-Locus Sequence Typing to compare **Cutibacterium acnes** strains and characterize antibiotic resistance. Additionally, skin tolerance of the topical application will be evaluated using a local tolerance scale assessing irritation, erythema, and desquamation at the time of inclusion and at day 0. The trial is designed to provide comprehensive data on the efficacy of the benzoyl peroxide treatment in reducing bacterial load and preventing infections associated with shoulder prosthesis.