Evaluation of Preoperative Methylprednisolone Hemisuccinate and Hydrogen Succinate on Postoperative Complications in Elective Digestive Cancer Surgery

The primary objective of this study is to assess the impact of a **flash dose** of preoperative corticosteroids versus placebo on the onset of major complications after elective curative-intent surgery for **digestive cancer**. This evaluation is clinically relevant as it aims to determine whether corticosteroids can reduce postoperative complications, potentially improving surgical outcomes and patient recovery.

Secondary objectives include evaluating the efficacy of a preoperative flash dose of corticosteroids compared to placebo on:

• Overall survival at 3 years
• Disease-free survival at 3 years
• Postoperative infections at 30 days
• Intraabdominal infections at 30 days
• Hospital stay duration

Additionally, the study aims to assess the safety of a preoperative flash dose of corticosteroids. These secondary objectives are crucial for understanding the broader implications of corticosteroid use in surgical oncology, including long-term survival benefits and potential risks associated with their administration.

The clinical trial involves participants scheduled for **elective surgery** for digestive cancer, excluding purely hepatic surgery, with the aim of assessing the impact of a flash dose of preoperative corticosteroids versus placebo on the onset of major complications. The study population includes both male and female subjects aged 18 years and older, who are in general good health and have provided written informed consent. Participants are required to be affiliated with a national health insurance scheme. The trial does not include a vulnerable population. 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 impact of a **flash dose of corticosteroids** on the onset of major complications following elective curative-intent surgery for digestive cancer. This study is a randomized, double-blind, placebo-controlled trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thereby minimizing bias. The trial is expected to run from July 2019 to November 2026, with participant involvement lasting up to 30 days post-surgery.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as age (≥18 years), scheduled elective surgery for digestive cancer, and written informed consent. The primary endpoint is the frequency of patients experiencing major postoperative complications within 30 days, defined by a Clavien-Dindo grade greater than 2. Secondary endpoints include overall survival, disease-free survival, frequency of postoperative infections, and safety assessments such as hyperglycemia and electrolyte disorders.

Follow-up visits will occur at specified intervals 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, assessing the final outcomes and any adverse events. Participants may be withdrawn from the study early if they experience significant adverse effects or if they withdraw consent. The trial involves the administration of **sodium chloride** as a placebo and **methylprednisolone** as the active treatment, both delivered via intravenous infusion. The maximum treatment period for each participant is one day, with a maximum daily dose of 50 ml for sodium chloride and 20 mg/kg for methylprednisolone.

The clinical trial involves the administration of **SODIUM CHLORIDE** as a placebo treatment. This substance is provided in the form of a **solution for infusion**. The maximum daily dose is 50 ml, with a total dose not exceeding 50 ml over the treatment period. The administration route is via **intravenous infusion**, and the treatment duration is limited to one day. The sodium chloride solution serves as a control to evaluate the effects of the experimental treatments.

The experimental treatment includes **SOLUMEDROL 500 mg**, which contains the active substance **methylprednisolone hemisuccinate**. This medication is supplied as a **powder for solution injectable**, which is reconstituted into a solution for injection. The maximum daily dose is 20 mg/kg, with a total dose not exceeding 20 mg/kg over the treatment period. The administration is conducted through **intravenous infusion**, and the treatment is administered for a single day. This corticosteroid is used to assess its impact on reducing major complications following elective curative-intent surgery for digestive cancer.

Another experimental treatment involves **METHYLPREDNISOLONE VIATRIS 500 mg**, containing the active substance **methylprednisolone hydrogen succinate**. Similar to Solumedrol, it is provided as a **powder for solution injectable** and is administered as a solution for injection. The dosing regimen is identical, with a maximum daily dose of 20 mg/kg and a total dose not exceeding 20 mg/kg, administered via **intravenous infusion** over a single day. This treatment is also evaluated for its efficacy in reducing postoperative complications in the specified surgical context.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the frequency of patients experiencing postoperative major complications within 30 days after surgery, defined as complications with a Clavien-Dindo grade greater than 2. Secondary endpoints include overall survival at 3 years, disease-free survival at 3 years, frequency of postoperative infections within 30 days, frequency of intraabdominal infections within 30 days, and the number of hospitalization days. In the event of a patient's death, they will be considered hospitalized until day 30. Additionally, safety will be evaluated by monitoring the frequency and type of side effects, such as **hyperglycemia** and electrolyte disorders, assessed through blood samples within the first 24 postoperative hours, and wound healing assessed by clinical inspection at the day 30 follow-up.