Evaluation of Hydrocortisone, Octreotide, and Teres Ligament Patch in Reducing Postoperative Complications Following High-Risk Pancreaticoduodenectomy

The primary objective of the PANENCA trial is to evaluate the effect of a combined treatment regimen, referred to as the **HOP bundle**, which includes hydrocortisone, octreotide, and a teres patch, on major complications following pancreatoduodenectomy. This surgical procedure is often performed for **pancreatic head carcinoma** or **intraductal papillary mucinous neoplasms (IPMN)**. The clinical relevance of this study lies in its potential to reduce postoperative complications, which are significant concerns in high-risk surgical patients undergoing pancreatoduodenectomy.

Secondary objectives include assessing the impact of the HOP bundle on the incidence of postoperative pancreatic fistulas, specifically those classified as grade B/C. These fistulas are a common and serious complication after pancreatic surgery, and their prevention could significantly improve patient outcomes and reduce healthcare burdens.

The clinical trial involves participants diagnosed with **pancreatic conditions** necessitating pancreaticoduodenectomy, such as pancreatic head carcinoma or intraductal papillary mucinous neoplasms (IPMN). The study population includes both male and female subjects, aged over 18 years, with no vulnerable populations selected. The sponsor has not provided the total number of participants. Participants were selected based on specific criteria, including undergoing elective pancreatoduodenectomy for any indication, with a pancreatic duct diameter of 3mm or less as determined by preoperative CT or MRI. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The sponsor has not disclosed further details regarding the general health status of the participants.

The clinical trial is designed as an **international randomized controlled multicenter trial** to evaluate the efficacy of a combined treatment approach, including **hydrocortisone**, **octreotide**, and a teres ligament patch, in preventing major complications following pancreatoduodenectomy. The trial will involve patients undergoing elective pancreatoduodenectomy for conditions such as pancreatic head carcinoma or intraductal papillary mucinous neoplasms. The study will be conducted over an estimated period from May 2025 to May 2027, with participant recruitment starting in May 2025. The trial is classified as a Phase 4, low-intervention study, adhering to the European Clinical Trials Regulation criteria.

Participants will be randomly assigned to receive the investigational treatment or standard care, ensuring a double-blind methodology to maintain objectivity. The primary endpoint is the rate of major complications, defined by a Clavien-Dindo score of III or higher and/or the need for postoperative abdominal drain placement. Secondary endpoints include rates of postoperative pancreatic fistula, delayed gastric emptying, post-pancreatectomy hemorrhage, and other complications as per the International Study Group for Pancreatic Surgery definitions.

The study will commence with an inclusion (screening) visit to assess eligibility based on criteria such as age over 18 years, pancreatic duct diameter ≤ 3mm, and the indication for pancreatoduodenectomy. Follow-up visits will be scheduled to monitor the participants' progress, assess the occurrence of any adverse drug reactions, and evaluate the primary and secondary endpoints. The end-of-study visit will conclude the participant's involvement, with data collection on outcomes such as functional recovery time, length of hospital stay, and mortality rates.

Participant involvement is expected to last for the duration of the treatment period, with a maximum treatment period of one month. Conditions that may lead to early termination from the study include the occurrence of severe adverse reactions or withdrawal of consent by the participant. The trial aims to provide robust scientific evidence on the safety and efficacy of the combined treatment approach, contributing to improved postoperative outcomes in patients undergoing high-risk pancreatoduodenectomy.

The clinical trial involves the administration of **Octreotide Lyomark**, a **somatostatin analogue** used for hormonal regulation and symptomatic treatment. The pharmaceutical form of this medication is a **solution for injection**, with the active substance being **octreotide acetate**. The medication is administered subcutaneously at a concentration of 0.1 mg/ml. The maximum daily dose is 1.5 mg, with a total maximum dose of 10.5 mg over the treatment period. The treatment duration is limited to one day. The product is manufactured by Lyomark Pharma GmbH and is not a pediatric formulation. Participant compliance with the dosing schedule will be monitored throughout the trial.

Additionally, the trial includes the use of **Solu-Cortef**, a corticosteroid with anti-inflammatory and immunosuppressive properties. The active substance in this medication is **hydrocortisone**, and it is provided as a powder for injection solution. The administration route is intravascular, with a dosage of 100 mg per injection. The maximum daily dose is 500 mg, and the total maximum dose is 3000 mg, also over a one-day treatment period. Solu-Cortef is produced by Pfizer B.V. and is not formulated for pediatric use. Compliance with the administration protocol will be closely monitored to ensure adherence to the study's dosing regimen.

The efficacy of the PANENCA trial will be assessed through a series of predefined primary and secondary endpoints. The primary endpoint is the rate of major complications, which is defined as a Clavien-Dindo score of ≥III and/or the need for postoperative abdominal drain placement. This endpoint will provide a direct measure of the treatment's impact on significant postoperative complications following pancreatoduodenectomy.

Secondary endpoints include a comprehensive range of postoperative outcomes, such as the rate of postoperative pancreatic fistula (POPF) grade B/C, delayed gastric emptying (DGE), post-pancreatectomy hemorrhage (PPH), chyle leakage (CL), bile leakage (BL), and post-pancreatectomy acute pancreatitis (PPAP). These will be evaluated according to the definitions provided by the International Study Group for Pancreatic Surgery (ISGPS). Additional secondary endpoints include the incidence of reinterventions during admission or readmission, adverse drug reactions to hydrocortisone and **octreotide**, multi-organ failure, ICU admissions, time to functional recovery, length of hospital stay, readmission within 90 days post-surgery, and both in-hospital and 90-day mortality rates.

The collection and analysis of these endpoints will be conducted at various timepoints throughout the trial, ensuring a thorough evaluation of the treatment's efficacy. The trial will utilize validated scales and definitions to ensure consistency and reliability in the assessment of these clinical outcomes. The data collected will be analyzed to determine the effectiveness of the HOP bundle in reducing major complications and improving recovery following high-risk pancreatoduodenectomy.