Evaluation of Perioperative Hydrocortisone Infusion Versus Placebo in Patients Undergoing Pancreatic Resection: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to assess the **efficacy** of the treatment strategy with hydrocortisone infusions in comparison to placebo in patients undergoing pancreatic resection. This evaluation is clinically relevant as it aims to determine the potential benefits of hydrocortisone in improving surgical outcomes and patient recovery in a high-risk surgical population.

Secondary objectives include:

• Assessing the efficacy of per protocol hydrocortisone infusions in comparison to placebo in high-risk patients with planned surgery, as referenced in published data.
• Evaluating the efficacy of the treatment strategy with hydrocortisone infusions in comparison to placebo across multiple parameters.
• Assessing the safety of hydrocortisone infusions in comparison to placebo, ensuring that the treatment does not introduce additional risks to patients.

The sponsor does not provide information regarding the total number of participants in this clinical trial. The study population includes both **male** and **female** patients aged 18 years and older, with no upper age limit specified. Participants are individuals scheduled for an elective **pancreatoduodenectomy**, irrespective of the underlying indication. The trial does not involve a vulnerable population. Participants are required to provide written informed consent in accordance with international guidelines and local laws, and they must have the ability to comprehend the nature of the trial and adhere to trial-related procedures. No specific lifestyle considerations such as diet or physical activity are mentioned in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** interventional study to evaluate the efficacy of perioperative **hydrocortisone** treatment in patients undergoing pancreatoduodenectomy. The trial aims to compare the treatment strategy with hydrocortisone infusions against a placebo. The study is set to commence recruitment on January 1, 2025, and is expected to conclude by January 1, 2030. Participants will be involved in the trial for a maximum treatment period of three days, with the primary endpoint being the occurrence of post-operative pancreatic fistula of grade B or worse within 90 days. Secondary endpoints include overall survival within one year, various grades of complications, and other post-surgical outcomes within 90 days.

Study visits will follow a structured sequence, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as planned elective pancreatoduodenectomy, age of 18 years or older, and the ability to provide informed consent. Follow-up visits will be scheduled to monitor the participants' health status and treatment efficacy, with the end-of-study visit marking the conclusion of the participant's involvement. The expected length of participant involvement is contingent upon the completion of the treatment period and follow-up assessments, with early termination possible in cases of non-compliance, withdrawal of consent, or adverse events that necessitate discontinuation.

The trial will utilize **sodium chloride** as a placebo and hydrocortisone as the active treatment, both administered via infusion. The maximum daily dose for each is set at 300 mg or ml, with a total dose not exceeding 900 mg or ml over the treatment period. The trial is categorized as a Phase II-III study, focusing on the perioperative management of patients undergoing pancreatic resection, specifically targeting the reduction of post-operative complications and improving overall surgical outcomes.

The clinical trial involves the administration of **Sodium Chloride** as a **solution for infusion**. This experimental medication is utilized as a placebo in the study. The **Sodium Chloride** solution is administered via infusion, with a maximum daily dose of 300 ml and a total maximum dose of 900 ml over a treatment period of up to 3 days. The solution is purely chemical in origin and is not a pediatric formulation. The administration of the solution is monitored to ensure participant compliance with the dosing schedule.

The experimental treatment in the trial is **Hydrocortisone**, marketed as **HYDROCORTISON Pfizer 100 mg sine Pulver und Lösungsmittel zur Herstellung einer Injektions- oder Infusionslösung**. This medication is provided as a **solution for injection/infusion** and is administered via infusion. The maximum daily dose is 300 mg, with a total maximum dose of 900 mg over a treatment period of up to 3 days. **Hydrocortisone** is a chemical substance and is not formulated for pediatric use. The trial aims to assess the efficacy of **Hydrocortisone** infusions compared to the placebo, with careful monitoring of dosing schedules and participant adherence to the treatment protocol.

The efficacy of the treatment strategy with **hydrocortisone** infusions in comparison to placebo will be assessed in this clinical trial. The primary endpoint for evaluating efficacy is the occurrence of post-operative pancreatic fistula of grade B or worse within 90 days. Secondary endpoints include overall survival within one year, grade IIIb or worse complications in the Clavien-Dindo Classification within 90 days, grade C or worse postpancreatectomy hemorrhage within 90 days, and other complications such as delayed gastric emptying, bile leak, chyle leak, completion pancreatectomy, surgical site infection, pneumonia, cholangitis, and postpancreatectomy acute pancreatitis, all within 90 days. Additionally, the incidence of (serious) adverse events will be monitored.