Comparative Efficacy of Cefoxitin Sodium Administration Regimens in Preventing Surgical Site Infections Post-Colorectal Surgery: A Multicenter RCT

The primary objective of this clinical trial is to demonstrate the **superiority** of a loading dose of cefoxitin followed by continuous infusion over standard of care boluses in reducing surgical site infections (SSI) within 30 days after colorectal surgery. This is clinically relevant as it aims to improve postoperative outcomes and reduce the incidence of infections, which can lead to complications and prolonged recovery times.

Secondary objectives include evaluating the incidence of individual types of SSI, surgical reintervention, anastomotic leak, and postoperative complications according to the Dindo and Clavien classification. Additionally, the study will assess the incidence of **Clostridium difficile** infection, hospital readmission, unexpected admission to the ICU, and the duration of hospital stay. Postoperative mortality and adverse events during antibiotic administration will also be monitored. These secondary objectives provide a comprehensive assessment of the potential benefits and risks associated with the intervention, contributing to a better understanding of its overall impact on patient health and healthcare resource utilization.

The clinical trial involves **adult patients** aged 18 years and older who are undergoing **colorectal surgery** with a predictable duration of more than 90 minutes. The study population includes both male and female participants, and it is noted that a vulnerable population is selected. Participants must be free individuals, not under guardianship, curatorship, or subordination, and must have given their informed consent. Additionally, they should be benefiting from a Social Security system or through a third party. The sponsor has not provided information regarding the total number of participants. The trial aims to assess the effectiveness of a loading dose of cefoxitin followed by continuous infusion compared to standard care boluses in reducing surgical site infections within 30 days post-surgery.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy of a loading dose of **cefoxitin sodium** followed by continuous infusion compared to standard bolus administration in preventing surgical site infections (SSI) in patients undergoing colorectal surgery. The trial aims to demonstrate the superiority of the continuous infusion method in reducing SSI within 30 days post-surgery. The study will involve adult patients aged 18 years and older who are scheduled for colorectal surgery with an expected duration of more than 90 minutes. Participants must be free from guardianship, have given informed consent, and be covered by a Social Security system.

The trial will span from the estimated recruitment start date of June 22, 2023, to the estimated end date of March 22, 2027. Participants will be involved in the study for a maximum treatment period of one day, with the primary endpoint being the proportion of patients experiencing any SSI within 30 days post-surgery. Secondary endpoints include the incidence of different types of SSI, surgical reintervention rates, anastomotic leaks, postoperative complications, and other related outcomes.

Study visits will follow a structured sequence, beginning with an inclusion (screening) visit to assess eligibility based on the inclusion criteria. Follow-up visits will be conducted to monitor the participants' health status and collect data on the primary and secondary endpoints. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any adverse events are addressed. Participants may be terminated early from the study if they withdraw consent, experience significant adverse events, or if the investigator deems it necessary for their safety.

The clinical trial involves the administration of **CEFOXITIN PANPHARMA 1 g**, a **powder for solution injectable (IV)**, which contains the active substance **cefoxitin sodium**. This medication is classified under the ATC code **J01DA05**, indicating its use as an antibacterial for systemic use. The pharmaceutical form is a solution for injection, and it is administered intravenously. The maximum daily dose is 4 grams, with a total maximum dose of 4 grams over a treatment period of one day. The trial aims to evaluate the efficacy of a loading dose of cefoxitin followed by continuous infusion compared to standard bolus administration in preventing surgical site infections in colorectal surgery.

Additionally, the trial utilizes **CHLORURE DE SODIUM 0,9 % AGUETTANT**, a **solution for infusion** containing the active substance **sodium chloride**. This product is used as an electrolyte solution and is administered intravenously. The maximum daily dose is 100 milliliters, with a total maximum dose of 100 milliliters over a treatment period of one day. This solution serves as a non-experimental treatment, providing a standard-of-care therapy to maintain electrolyte balance during the trial. Both substances are chemically derived and are not formulated for pediatric use. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

Efficacy in this clinical trial will be assessed by evaluating the primary and secondary endpoints related to the prevention of surgical site infections (SSI) in patients undergoing colorectal surgery. The primary endpoint is the proportion of patients experiencing any SSI within 30 days post-surgery. Secondary endpoints include the proportion of patients with specific types of SSI (superficial, deep, and organ-space infections), surgical reintervention rates, incidence of anastomotic leaks, and postoperative complications classified according to the Dindo and Clavien system. Additional secondary endpoints encompass the proportion of patients with **Clostridium difficile** infection, hospital readmission rates, unexpected ICU admissions, duration of hospital stay, hospital-free days, all-cause mortality, and the occurrence of perioperative adverse events.

The trial will employ a multicentre, double-blind, randomized controlled design to compare the efficacy of a loading dose of cefoxitin followed by continuous infusion against standard care boluses. Efficacy parameters will be collected and analyzed at specified time points, with the primary endpoint being assessed within 30 days following surgery. The trial aims to demonstrate the superiority of the continuous infusion method in reducing SSI rates, thereby improving patient outcomes in colorectal surgery.