Ignite Creation Date:
2025-12-24 @ 6:38 PM
Ignite Modification Date:
2025-12-24 @ 6:38 PM
Study NCT ID:
NCT07262957
Status:
RECRUITING
Last Update Posted:
2025-12-22
First Post:
2025-11-25
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Preventing Postoperative Complications in Patients Undergoing High-risk Pancreatoduodenectomy With a Bundle Approach Including Hydrocortisone, Octreotide, and the Teres Ligament Patch (PANENCA)
Sponsor:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Organization:
Study Overview
Official Title:
Preventing Postoperative Complications in Patients Undergoing High-risk Pancreatoduodenectomy With a Bundle Approach Including Hydrocortisone, Octreotide, and the Teres Ligament Patch (PANENCA): an International Randomized Controlled Multicenter Trial
Status:
RECRUITING
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PANENCA
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.
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.
Detailed Description:
The PANENCA trial is an international, multicenter, randomized controlled superiority trial designed to evaluate whether a standardized perioperative bundle approach reduces major postoperative complications in patients undergoing pancreatoduodenectomy who are at high risk for postoperative pancreatic fistula (POPF). High risk is defined preoperatively by a small main pancreatic duct diameter (≤3 mm) on cross-sectional imaging, which is associated with soft pancreatic parenchyma and an increased risk of anastomotic failure.
POPF remains the leading cause of morbidity and mortality following pancreatoduodenectomy. Several low-cost and widely available interventions have individually demonstrated effectiveness in reducing POPF or its sequelae; however, these measures have not been implemented consistently, systematically evaluated in a large international randomized trial, nor combined into a standardized perioperative strategy. The PANENCA trial therefore evaluates a bundled intervention (the HOP bundle) consisting of the following components:
1. Hydrocortisone, administered intravenously starting during induction of anesthesia to attenuate the postoperative inflammatory response, which is considered a key contributor to the development of POPF. Hydrocortisone is administered at a dose of 100 mg three times daily for three days, resulting in a total of 9 doses.
2. Octreotide, administered subcutaneously starting during induction of anesthesia, to reduce exocrine pancreatic secretion during the early postoperative period. Octreotide is administered at a dose of 0.1 mg three times daily for up to seven days or until earlier discharge, with a maximum of 21 doses.
3. A ligamentum teres hepatis patch, applied intraoperatively to mechanically protect the gastroduodenal artery stump from enzymatic erosion in the event of a POPF. The ligamentum teres is positioned between the gastroduodenal artery stump and the pancreatojejunostomy, functioning as an interpositional layer or wrap around one or both structures.
These interventions have potential complementary and non-overlapping mechanisms of action and are supported by prior randomized trials and meta-analyses. All investigational medicinal products are authorized and are used within approved or evidence-based indications.
Eligible patients are randomized in a 1:1 ratio prior to surgery to receive either the HOP bundle in addition to standard perioperative care or standard perioperative care alone. Randomization is stratified by participating center to account for potential inter-center variability. The trial is classified as a low-interventional clinical trial according to the European Union Clinical Trials Regulation (EU No 536/2014), as it uses authorized medicinal products, evidence-based dosing regimens, and does not require additional diagnostic or monitoring procedures beyond standard clinical practice.
Patients are followed from the day of surgery until hospital discharge, with additional follow-up to 90 days postoperatively for assessment of postoperative complications, readmissions, and mortality. No additional outpatient visits or diagnostic procedures are mandated beyond routine postoperative care.
The trial is powered to detect a superiority effect of the HOP bundle on the primary endpoint of major postoperative complications. Sample size calculations are based on contemporary national audit data demonstrating a substantially higher complication rate in patients with small pancreatic ducts. Allowances are made for intraoperative non-resection due to metastatic disease and for minimal loss to follow-up. A predefined interim analysis for futility and safety is planned. Detailed statistical methodology, including handling of missing data and definition of analysis populations, is specified in the statistical analysis section of the protocol.
Data are collected prospectively using a standardized electronic case report form (eCRF). Variables collected include baseline characteristics, intraoperative details, postoperative outcomes, and adverse events, all of which are routinely recorded as part of standard surgical care. Definitions of postoperative complications follow internationally accepted criteria, including those of the International Study Group of Pancreatic Surgery (ISGPS).
Data quality is ensured through predefined range and consistency checks within the eCRF system, central data monitoring, and on-site or remote monitoring in accordance with Good Clinical Practice (GCP). Source data verification is performed on a risk-based basis by comparison with medical records and operative reports. Serious adverse events and suspected unexpected serious adverse reactions are reported in accordance with regulatory requirements and overseen by an independent Data Safety Monitoring Board.
Both hydrocortisone and octreotide have well-established safety profiles. Given the short duration and low dosing used in this trial, the additional risk to participants is considered minimal. Postoperative monitoring, including glucose monitoring and routine laboratory assessments, follows standard clinical practice. Criteria for temporary trial suspension or early termination are predefined, and safety oversight is provided by an independent monitoring committee.
The study is conducted in accordance with the Declaration of Helsinki, International Council for Harmonisation Good Clinical Practice (ICH-GCP), and applicable national and European regulations. Written informed consent is obtained from all participants prior to enrollment. Patient representatives were involved in the design of the trial and will remain engaged throughout its conduct and dissemination of results.
Upon completion, study results will be submitted for publication in peer-reviewed journals and presented at international scientific meetings. A summary of results will be made publicly available in accordance with applicable transparency regulations.
POPF remains the leading cause of morbidity and mortality following pancreatoduodenectomy. Several low-cost and widely available interventions have individually demonstrated effectiveness in reducing POPF or its sequelae; however, these measures have not been implemented consistently, systematically evaluated in a large international randomized trial, nor combined into a standardized perioperative strategy. The PANENCA trial therefore evaluates a bundled intervention (the HOP bundle) consisting of the following components:
1. Hydrocortisone, administered intravenously starting during induction of anesthesia to attenuate the postoperative inflammatory response, which is considered a key contributor to the development of POPF. Hydrocortisone is administered at a dose of 100 mg three times daily for three days, resulting in a total of 9 doses.
2. Octreotide, administered subcutaneously starting during induction of anesthesia, to reduce exocrine pancreatic secretion during the early postoperative period. Octreotide is administered at a dose of 0.1 mg three times daily for up to seven days or until earlier discharge, with a maximum of 21 doses.
3. A ligamentum teres hepatis patch, applied intraoperatively to mechanically protect the gastroduodenal artery stump from enzymatic erosion in the event of a POPF. The ligamentum teres is positioned between the gastroduodenal artery stump and the pancreatojejunostomy, functioning as an interpositional layer or wrap around one or both structures.
These interventions have potential complementary and non-overlapping mechanisms of action and are supported by prior randomized trials and meta-analyses. All investigational medicinal products are authorized and are used within approved or evidence-based indications.
Eligible patients are randomized in a 1:1 ratio prior to surgery to receive either the HOP bundle in addition to standard perioperative care or standard perioperative care alone. Randomization is stratified by participating center to account for potential inter-center variability. The trial is classified as a low-interventional clinical trial according to the European Union Clinical Trials Regulation (EU No 536/2014), as it uses authorized medicinal products, evidence-based dosing regimens, and does not require additional diagnostic or monitoring procedures beyond standard clinical practice.
Patients are followed from the day of surgery until hospital discharge, with additional follow-up to 90 days postoperatively for assessment of postoperative complications, readmissions, and mortality. No additional outpatient visits or diagnostic procedures are mandated beyond routine postoperative care.
The trial is powered to detect a superiority effect of the HOP bundle on the primary endpoint of major postoperative complications. Sample size calculations are based on contemporary national audit data demonstrating a substantially higher complication rate in patients with small pancreatic ducts. Allowances are made for intraoperative non-resection due to metastatic disease and for minimal loss to follow-up. A predefined interim analysis for futility and safety is planned. Detailed statistical methodology, including handling of missing data and definition of analysis populations, is specified in the statistical analysis section of the protocol.
Data are collected prospectively using a standardized electronic case report form (eCRF). Variables collected include baseline characteristics, intraoperative details, postoperative outcomes, and adverse events, all of which are routinely recorded as part of standard surgical care. Definitions of postoperative complications follow internationally accepted criteria, including those of the International Study Group of Pancreatic Surgery (ISGPS).
Data quality is ensured through predefined range and consistency checks within the eCRF system, central data monitoring, and on-site or remote monitoring in accordance with Good Clinical Practice (GCP). Source data verification is performed on a risk-based basis by comparison with medical records and operative reports. Serious adverse events and suspected unexpected serious adverse reactions are reported in accordance with regulatory requirements and overseen by an independent Data Safety Monitoring Board.
Both hydrocortisone and octreotide have well-established safety profiles. Given the short duration and low dosing used in this trial, the additional risk to participants is considered minimal. Postoperative monitoring, including glucose monitoring and routine laboratory assessments, follows standard clinical practice. Criteria for temporary trial suspension or early termination are predefined, and safety oversight is provided by an independent monitoring committee.
The study is conducted in accordance with the Declaration of Helsinki, International Council for Harmonisation Good Clinical Practice (ICH-GCP), and applicable national and European regulations. Written informed consent is obtained from all participants prior to enrollment. Patient representatives were involved in the design of the trial and will remain engaged throughout its conduct and dissemination of results.
Upon completion, study results will be submitted for publication in peer-reviewed journals and presented at international scientific meetings. A summary of results will be made publicly available in accordance with applicable transparency regulations.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: