Evaluation of Linezolid Versus Vancomycin for Surgical Site Infection Prophylaxis in Surgical Patients: A Non-Inferiority Clinical Trial

The primary objective of this study is to demonstrate the **non-inferiority** of **linezolid** compared to **vancomycin** as surgical antibiotic prophylaxis for all types of surgery in terms of preventing surgical site infections (SSIs) at day-30 post-surgery. This is clinically relevant as it aims to establish an alternative prophylactic option that may offer similar efficacy in preventing SSIs, which are a significant concern in postoperative care.

Secondary objectives include:

• Comparing rates of SSIs at day-90 and day-365 between the two groups to assess non-inferiority.
• Evaluating compliance to treatment, delays in surgery onset, and hospital length of stay for superiority between the groups.
• Assessing in-hospital mortality rates, incidence and type of micro-organisms causing SSIs, and conducting a health economic analysis for superiority.
• Comparing the quality of life and patient satisfaction between the groups.

The clinical trial focuses on evaluating the efficacy of **linezolid** versus vancomycin for **surgical antibiotic prophylaxis**. The study population comprises adult patients aged 18 years and older, undergoing elective surgeries where vancomycin is recommended as an alternative to beta-lactams. Both male and female participants are included, and the trial does not involve a vulnerable population. Participants are selected based on specific criteria, including a known allergy to beta-lactams or suspected/proven MRSA colonization. The trial encompasses various surgical specialties such as neurological, cardiac, orthopedic, vascular, urology, ENT, maxillo-facial, or digestive surgeries. Lifestyle factors such as diet and physical activity are not specified. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the **non-inferiority** of **linezolid** compared to **vancomycin** for surgical antibiotic prophylaxis in preventing surgical site infections (SSIs) by day 30 post-surgery. This study employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The trial is expected to run from July 1, 2023, to July 31, 2026, with participant involvement lasting up to 30 days post-surgery.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), type of surgery, and known allergies. The primary inclusion criteria include adult patients undergoing elective surgeries where **vancomycin** is recommended as an alternative to beta-lactams, with a known allergy to beta-lactams or suspected/proven MRSA colonization. The screening visit will also involve obtaining informed consent and verifying social security affiliation.

Following the inclusion visit, participants will be randomized to receive either **linezolid** 1200 mg or **vancomycin** 30 mg/kg as a single dose via infusion. The primary endpoint is the rate of SSIs at day 30 post-surgery. Participants will have follow-up visits to monitor for any adverse events and assess the primary endpoint. The end-of-study visit will occur at day 30, where final assessments will be conducted to evaluate the presence of SSIs and any other relevant outcomes.

Participant involvement is expected to last for the duration of the 30-day post-surgery period. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that necessitate discontinuation of the study drug. The trial is categorized as a low-intervention study due to the single-dose administration and the low-risk profile of the participants.

The clinical trial involves the administration of **Linezolid Kabi 2 mg/ml solution for infusion** as the experimental medication. This pharmaceutical product is a solution for infusion, containing the active substance **linezolid**, a chemical compound. The maximum daily dose is 1200 mg, administered via infusion. The treatment period is limited to one day. The administration of the drug is monitored to ensure compliance with the dosing schedule.

In addition to the experimental treatment, the trial includes a comparator treatment using various formulations of **vancomycin** and **vancomycin hydrochloride**. These comparator products are provided in the form of powders for solution for infusion, with the active substances being chemical in origin. The maximum daily dose for these comparator treatments is 30 mg/kg, also administered via infusion, with a treatment period of one day. The comparator products include: VANCOMYCINE HIKMA 500 mg, VANCOMYCINE VIATRIS 500 mg, VANCOMYCINE VIATRIS 125 mg, Vancomycine MIP 500 mg, VANCOMYCINE SANDOZ 1 g, VANCOMYCINE VIATRIS 1000 mg, Vancomycine MIP 1000 mg, VANCOMYCINE SANDOZ 125 mg, VANCOMYCINE VIATRIS 250 mg, VANCOMYCINE SANDOZ 500 mg, VANCOMYCINE SANDOZ 250 mg, and VANCOMYCINE HIKMA 1000 mg. Each of these products is administered under strict compliance monitoring to ensure adherence to the dosing regimen.

The efficacy of the clinical trial will be assessed by evaluating the primary endpoint, which is the rate of surgical site infections (SSIs) at day 30 post-surgery. This trial aims to demonstrate the non-inferiority of **linezolid** compared to **vancomycin** as surgical antibiotic prophylaxis across various types of surgeries. The primary endpoint will be measured by comparing the incidence of SSIs in patients receiving linezolid 1200 mg with those receiving vancomycin 30 mg/kg. The assessment will be conducted at a specific time point, which is 30 days after the surgical procedure.