Preventing Postoperative Complications in Patients Undergoing High-risk Pancreatoduodenectomy With a Bundle Approach Including Hydrocortisone, Octreotide, and the Teres Ligament Patch (PANENCA)

Summary

The PANENCA trial aims to reduce postoperative complications in patients undergoing pancreatoduodenectomy (also known as a Whipple procedure), a complex surgical operation performed to remove tumors located in or near the head of the pancreas. One of the most frequent and serious complications after this surgery is postoperative pancreatic fistula (POPF), a leakage of pancreatic fluid from the surgical connection. POPF can lead to intra-abdominal infection, bleeding, and inflammation, often resulting in delayed recovery and postponement of subsequent oncological treatment. In severe cases, these complications may be life-threatening.

Patients with a small main pancreatic duct (3 millimeters or less) are known to have a substantially higher risk of developing POPF. Previous studies have shown that several existing interventions may reduce the risk or severity of these complications. These include hydrocortisone, a medication that suppresses postoperative inflammation; octreotide, a medication that reduces the production of pancreatic secretions; and a surgical technique known as the ligamentum teres hepatis patch, which uses the patient's own tissue to protect nearby blood vessels in the event of a pancreatic leak.

Because the development of pancreatic fistulas is multifactorial, the investigators hypothesize that a combined approach targeting different underlying mechanisms may provide a complementary and more effective protective effect than any single intervention alone. The PANENCA trial therefore evaluates whether the combined use of hydrocortisone, octreotide, and the ligamentum teres patch can reduce the rate of major postoperative complications after pancreatoduodenectomy.

Patients participating in the study are randomly assigned to receive either the combination treatment in addition to standard perioperative care or standard perioperative care alone. The study medications are administered only during the first postoperative days, and the surgical patch is applied during the operation itself. No additional tests, monitoring procedures, or hospital visits are required beyond routine clinical care.

This international, multicenter randomized trial includes patients at high risk for POPF who are undergoing pancreatoduodenectomy. The primary objective is to determine whether the combination treatment reduces the incidence of major postoperative complications. If proven effective, this bundle approach may be implemented more consistently across participating countries and incorporated into international clinical guidelines for pancreatic surgery.

Conditions

• Pancreas Head Cancer
• Pancreas Adenocarcinoma
• IPMN, Pancreatic
• Cholangio Carcinoma
• Ampulla of Vater Adenocarcinoma
• PDAC - Pancreatic Ductal Adenocarcinoma
• Duodenal Carcinoma
• Mucinous Cystic Neoplasm
• Neuro Endocrine Tumours
• Pancreatitis

Interventions

COMBINATION_PRODUCT

HOP bundle

Patients in the intervention group will receive the HOP bundle approach: * Hydrocortisone intravenous: 100mg hydrocortisone as sodium succinate i.v. starting during the induction of general anesthesia, administered every 8 hours until 2 days perioperative (last dose evening postoperative day 2) (total 9 dosages). * Octreotide subcutaneous: 0,1 mg every 8 hours during maximum 7 days, starting during the induction of general anesthesia, administered minimal 1 hour before surgery (to a maximum of 21 dosages or until earlier discharge). * Intraoperative coverage of the gastroduodenal artery stump using a teres ligament patch, separating it from the pancreato-enteric anastomosis.

Sponsors & Collaborators

• Erasmus Medical Center

  collaborator OTHER

• UMC Utrecht

  collaborator OTHER

• Medisch Spectrum Twente

  collaborator OTHER

• Jeroen Bosch Ziekenhuis

  collaborator OTHER

• Maastricht University Medical Center

  collaborator OTHER

• Radboud University Medical Center

  collaborator OTHER

• Isala

  collaborator OTHER

• Catharina Ziekenhuis Eindhoven

  collaborator OTHER

• Helsinki University Central Hospital

  collaborator OTHER

• Oslo University Hospital

  collaborator OTHER

• Karolinska University Hospital

  collaborator OTHER

• Sahlgrenska University Hospital

  collaborator OTHER

• University Hospital, Linkoeping

  collaborator OTHER

• Lund University Hospital

  collaborator OTHER

• Azienda Ospedaliera Universitaria Integrata Verona

  collaborator OTHER

• Azienda Ospedaliera di Padova

  collaborator OTHER

• San Raffaele University Hospital, Italy

  collaborator OTHER

• Leiden University Medical Center

  collaborator OTHER

• University Medical Center Groningen

  collaborator OTHER

• Clinical Cancer Hospital, Kyiv

  collaborator OTHER

• Rigshospitalet, Denmark

  collaborator OTHER

• University Hospital, Antwerp

  collaborator OTHER

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-09-01

Primary Completion

2027-09-01

Completion

2027-12-01

Countries

• Netherlands

Study Locations