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

NCT07262957 | Recruiting Phase 4 DMC

• 1 other identifier: 2024-519667-18-00
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Whipple; Pancreatoduodenectomy; POPF; Major complications; Fistula; ISGPS; Hydrocortisone; Octreotide; Ligament teres patch

Outcome Measures

Primary Outcomes (1)

• Major complications

  Rate of Major Complications, defined as a Clavien-Dindo score of ≥III and/or postoperative abdominal drain placement

  Until postoperative day 90

Secondary Outcomes (1)

• Postoperative Pancreatic Fistula (POPF)

  Until postoperative day 90

Study Arms (2)

Intervention arm (HOP bundle)

EXPERIMENTAL

Patients in the intervention group will receive the HOP bundle approach: a combination intervention of: Hydrocortisone, octreotide and the ligamentum teres patch

Combination Product: HOP bundle

Controle arm

NO INTERVENTION

Standard care

Interventions

HOP bundle COMBINATION_PRODUCT

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.

Also known as: Hydrocortisone, Octreotide, Ligament teres patch

Intervention arm (HOP bundle)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Elective pancreatoduodenectomy for any indication (both minimally invasive and open)
• Pancreatic duct diameter ≤ 3mm on preoperative CT or MRI\*
• years of age or older
• Signature of informed consent
• In the opinion of the investigator, the patient is eligible for the administration of hydrocortisone and octreotide, based on contraindications, warnings, and precautions as listed in the respective SmPCs

You may not qualify if:

• Age \< 18 years
• Pregnancy or current breastfeeding
• Known allergy or hypersensitivity to hydrocortisone or octreotide
• Systemic fungal infection
• Concomitant use of strong CYP3A4 inhibitors or moderate-to-strong inducers that cannot be discontinued (see CYTOCHROME P450 DRUG INTERACTION TABLE (iu.edu))
• Inhibitors must be discontinued ≥7 days before randomization
• Inducers must be discontinued ≥28 days before randomization

Sponsors & Collaborators

• Erasmus Medical Center: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• UMC Utrecht: collaborator
• Medisch Spectrum Twente: collaborator
• Jeroen Bosch Ziekenhuis: collaborator
• Maastricht University Medical Center: collaborator
• Radboud University Medical Center: collaborator
• Isala: collaborator
• Catharina Ziekenhuis Eindhoven: collaborator
• Helsinki University Central Hospital: collaborator
• Oslo University Hospital: collaborator
• Karolinska University Hospital: collaborator
• Sahlgrenska University Hospital: collaborator
• University Hospital, Linkoeping: collaborator
• Lund University Hospital: collaborator
• Azienda Ospedaliera Universitaria Integrata Verona: collaborator
• Azienda Ospedaliera di Padova: collaborator
• San Raffaele University Hospital, Italy: collaborator
• Leiden University Medical Center: collaborator
• University Medical Center Groningen: collaborator
• Clinical Cancer Hospital, Kyiv: collaborator
• Rigshospitalet, Denmark: collaborator
• University Hospital, Antwerp: collaborator

Study Sites (1)

Amsterdam UMC

Amsterdam, Netherlands

RECRUITING

MeSH Terms

Conditions

Pancreatic Intraductal Neoplasms; Duodenal Neoplasms; Pancreatitis; Fistula

Interventions

Hydrocortisone; Octreotide

Condition Hierarchy (Ancestors)

Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Duodenal Diseases; Intestinal Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Peptides, Cyclic; Macrocyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Sterre Bosscha, BSc

CONTACT

+31622534263; s.r.bosscha@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Model Details: The PANENCA trial is an international, multicenter, randomized controlled trial with 1:1 parallel allocation to the intervention group (HOP bundle) or the control group (standard care).

Study Record Dates

• First Submitted: November 25, 2025
• First Posted: December 4, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 22, 2025

Record last verified: 2025-12

Locations

NL (1)