Evaluation of Methylprednisolone on Postoperative Recovery in Elderly Patients Undergoing Major Surgery

The primary objective of the CORTERAS study is to evaluate the effect of moderate dose **corticosteroids** on early post-operative outcomes, with a specific focus on muscle weakness, in elderly patients aged 60 years and older undergoing complex major surgery. This is clinically relevant as muscle weakness post-surgery can significantly impact recovery and quality of life in this patient population.

Secondary objectives include monitoring outcomes related to early recovery after surgery, investigating the effects on systemic inflammation and coagulation, and assessing functional and clinical outcomes. Additionally, biochemical analysis and markers of coagulation will be evaluated to provide a comprehensive understanding of the corticosteroids' impact on the recovery process.

The clinical trial involves a study population of **elderly patients** aged 60 years or older, both male and female, who are scheduled for complex major surgical procedures. The trial aims to evaluate the effect of moderate dose corticosteroids on early post-operative outcomes, particularly focusing on muscle weakness. The specific surgeries include robotic-assisted laparoscopic radical prostatectomies, peripheral vascular surgeries such as femoral popliteal bypass, on and off pump coronary bypass surgeries, thoracoscopic lung resection surgeries, laparoscopic colorectal surgeries, and minimally invasive valve repair or replacement surgeries. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on their age and the requirement for complex major surgery, with no vulnerable populations being included. Lifestyle considerations such as diet, physical activity, or habits have not been specified in the available data.

This clinical trial is designed to evaluate the effect of moderate dose **corticosteroids** on early post-operative outcomes, specifically focusing on muscle weakness in elderly patients aged 60 years or older undergoing complex major surgery. The trial is a prospective, randomized, double-blind, controlled study, ensuring that neither the participants nor the researchers know who is receiving the active treatment or the placebo, which in this case is **sodium chloride** 0.9% intravenous infusion. The trial is expected to run from April 1, 2022, to August 31, 2025, with the primary endpoint being postoperative muscle strength. Secondary endpoints include assessments of postoperative muscle function, lung function, cognitive status, fatigue, quality of recovery, pain, postoperative nausea and vomiting, and biochemical analyses.

Participants will be involved in the study for a maximum treatment period of one day, with the possibility of early termination if they do not meet the inclusion criteria or if adverse events occur. The study visits will begin with a screening visit to confirm eligibility based on criteria such as age and scheduled surgery type. Follow-up visits will be conducted to monitor the primary and secondary endpoints, with the final visit marking the end of the study. The trial will include various types of major surgeries, such as robotic-assisted laparoscopic radical prostatectomies, peripheral vascular surgeries, coronary bypass surgeries, thoracoscopic lung resections, laparoscopic colorectal surgeries, and minimally invasive valve repairs or replacements. The study aims to provide insights into the potential benefits of corticosteroids in improving early recovery outcomes in this patient population.

The clinical trial involves the administration of **methylprednisolone**, marketed under the name Solu-Medrol S.A.B. (= Sine Alcohol Benzylicus) 125 mg. This experimental medication is provided in the form of a powder and solvent for solution for injection. The pharmaceutical form is a **solution for injection**, and it is administered via **intravenous administration**. The maximum daily dose is 500 mg, with a total dose not exceeding 500 mg over the treatment period. The treatment period is limited to one day. The active substance, methylprednisolone, is of chemical origin and is classified under the ATC code H02AB04. The product is manufactured by Pfizer S.A. and is authorized for use in Belgium.

In addition to the experimental treatment, the study utilizes **sodium chloride** 0.9% as a non-experimental treatment. This is provided as a **solution for infusion** and is administered intravenously. The maximum daily dose is 200 ml, with a total dose not exceeding 200 ml over the treatment period, which is also limited to one day. Sodium chloride serves as a standard-of-care therapy and is classified under the ATC code B05BB01, which pertains to electrolytes. The product is manufactured by Fresenius Kabi Limited and is authorized for use in the United Kingdom.

Efficacy in the clinical trial titled "The effect of corticosteroids on early recovery after major surgery in elderly patients: CORTERAS study" will be assessed using both primary and secondary endpoints. The primary endpoint is the evaluation of postoperative muscle strength. Secondary endpoints include assessments of postoperative muscle function, lung function, cognitive status using the S5Q, fatigue levels via the Chalder fatigue questionnaire, quality of recovery through the QoR-15 questionnaire, health status with the EQ5D, pain intensity using the NRS pain score (0-10), incidence of postoperative nausea and vomiting (PONV), and biochemical analyses including markers of coagulation.

The trial aims to evaluate the effect of moderate dose corticosteroids on early postoperative outcomes, particularly focusing on muscle weakness in patients aged 60 years or older undergoing complex major surgery. The efficacy parameters will be collected and analyzed at specified timepoints throughout the trial duration, which is estimated to conclude by August 31, 2025. The study will utilize validated scales and questionnaires to ensure accurate and reliable measurement of the endpoints. The trial is categorized as a Phase IV study, indicating the investigation of potential benefits of an already authorized investigational medicinal product (IMP).