Technical Strategies for Pancreatic Fistula Prevention After Pancreaticoduodenectomy in High-risk Pancreatic Remnant (PREP)

Technical Strategies for Pancreatic Fistula Prevention After Pancreaticoduodenectomy in High-risk Pancreatic Remnant: a Risk-adjusted Randomized Controlled Trial

This trial will investigate what surgical technique between pancreaticogastrostomy and pancreaticojejunostomy with transanastomotic externalized drains is associated with the lowest rate of pancreatic fistula after pancreaticoduodenectomy in case of high-risk pancreatic remnants.

Study Overview

• Status: Completed
• Conditions: Pancreatic Fistula
• Intervention / Treatment: Procedure: Pancreaticogastrostomy with external drain; Procedure: Pancreaticojejunostomy with transanastomotic drain

Detailed Description

Pancreatic fistula is the major determinant of outcome after pancreaticoduodenectomy. Several strategies to reduce the burden of this complication have been proposed in the last decade. A definite answer about what is the best technique to approach a high-risk pancreatic stump is still needed. Both pancreaticogastrostomy and pancreaticojejunostomy with transanastomotic externalized drains have been proposed in this setting, but often studies do not provide a reliable risk stratification and result are extremely variable.

The aim of this trial is to evaluate what surgical technique, between pancreaticogastrostomy and pancreaticojejunostomy with transanastomotic externalized drains, is associated with the lowest rate of pancreatic fistula in case of high-risk pancreatic remnants. Risk stratification will be provided through the Fistula Risk Score, a clinical risk score that has been extensively validated.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Verona, Italy, 37134
    • Ospedale Policlinico GB Rossi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All the patients undergoing pancreaticoduodenectomy (only Whipple or Traverso) for all kind of pancreatic disease (benign, malignant or premalignant).
• Patients able to give their informed consent

Exclusion criteria

• Informed consent withdrawal
• Impossibility to undergo surgery for any reason
• Use of glues or biological matrices to protect the anastomosis
• Fistula Risk Score < 7
• Post-operative octreotide analogues administration (only prophylactic use, therapeutic use allowed)
• Wrong randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pancreaticogastrostomy; Pancreaticogastrostomy with external drain	Procedure: Pancreaticogastrostomy with external drain; Pancreatico-enteric anastomosis is provided according to the "Bassi technique", pancreatic remnant is pushed into the gastric cavity through a posterior gastrotomy. An externalized drain is placed into the main pancreatic duct.
Active Comparator: Pancreaticojejunostomy; Pancreaticojejunostomy with transanastomotic drain	Procedure: Pancreaticojejunostomy with transanastomotic drain; Pancreatico-enteric anastomosis is provided through a double-layer, duct-to-mucosa anastomosis with a transanastomotic externalized drain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative Pancreatic Fistula (POPF)	Presence of Amylase > 3 times the upper limit of normal in surgical drains at or by post-operative day 3 (POD) determining a clinically relevant change in patient's management	30 days post-operative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
POPF severity	POPF grade B and grade C rates	30 days post-operative
Length of Hospital Stay	calculated from the day of surgery to the day of discharge, adding up the days after a possible re-admission	1 year
Mortality	Death related to surgical morbidity	90 days
Post-Pancreatectomy Hemorrhage	As defined by the International Study Group for Pancreatic Surgery (ISGPS), grade A, B and C rates	90 days
Delayed Gastric Emptying	As defined by ISGPS, grade A, B and C rates	90 days
Biliary fistula	Output of bile from drains on or by POD 3, pancreaticojejunostomy leak should be ruled out	90 days
Gastrojejunal/Duodenojejunal fistula	Fistula from gastro/duodenojejunostomy	90 days
Abdominal abscess	Collection >5cm in size, containing gas bubbles, determining systemic signs of infection	90 days
Acute pancreatitis	Altered serum amylase count on POD 0 or POD 1	1 day post index surgery
Wound infection	Superficial and Deep Surgical Site Incisional Infection as defined by the Center for Disease Control and Prevention	90 days
Blood transfusions	Need and number of packed red blood cells transfused	90 days
Myocardial infarction	Myocardial necrosis	90 days
Acute Kidney Failure	Abrupt change in serum creatinine >1.5 baseline value	90 days
Pulmonary Embolism	Blood clots in the pulmonary arterial system	90 days
Pneumonia	Bacterial infection of the lungs	90 days
Respiratory insufficiency	Need for re-intubation	90 days
Urinary Tract Infection	Bacterial infection of the urinary tract	90 days
Cerebrovascular accidents	Stroke, hemorrhage, brain death	90 days
Reoperation	Need for new surgery due to severe morbidity	90 days
Readmission	New admission within 30-days of discharge from hospital	30 days after hospital discharge
Time-to-adjuvant therapy	Time form index operation to the beginning of adjuvant treatment (only for malignancy)	1 year

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Universitaria Integrata Verona
• Investigators: Principal Investigator: Claudio Bassi, MD, Università degli studi di Verona

Publications and helpful links

General Publications

• McMillan MT, Ecker BL, Behrman SW, Callery MP, Christein JD, Drebin JA, Fraker DL, Kent TS, Lee MK, Roses RE, Sprys MH, Vollmer CM Jr. Externalized Stents for Pancreatoduodenectomy Provide Value Only in High-Risk Scenarios. J Gastrointest Surg. 2016 Dec;20(12):2052-2062. doi: 10.1007/s11605-016-3289-6. Epub 2016 Oct 11.
• Bassi C, Molinari E, Malleo G, Crippa S, Butturini G, Salvia R, Talamini G, Pederzoli P. Early versus late drain removal after standard pancreatic resections: results of a prospective randomized trial. Ann Surg. 2010 Aug;252(2):207-14. doi: 10.1097/SLA.0b013e3181e61e88.
• Callery MP, Pratt WB, Kent TS, Chaikof EL, Vollmer CM Jr. A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. J Am Coll Surg. 2013 Jan;216(1):1-14. doi: 10.1016/j.jamcollsurg.2012.09.002. Epub 2012 Nov 2.
• Hallet J, Zih FS, Deobald RG, Scheer AS, Law CH, Coburn NG, Karanicolas PJ. The impact of pancreaticojejunostomy versus pancreaticogastrostomy reconstruction on pancreatic fistula after pancreaticoduodenectomy: meta-analysis of randomized controlled trials. HPB (Oxford). 2015 Feb;17(2):113-22. doi: 10.1111/hpb.12299. Epub 2014 Jul 7.
• Wang SE, Chen SC, Shyr BU, Shyr YM. Comparison of Modified Blumgart pancreaticojejunostomy and pancreaticogastrostomy after pancreaticoduodenectomy. HPB (Oxford). 2016 Mar;18(3):229-35. doi: 10.1016/j.hpb.2015.09.007. Epub 2015 Nov 17.
• Andrianello S, Marchegiani G, Malleo G, Masini G, Balduzzi A, Paiella S, Esposito A, Landoni L, Casetti L, Tuveri M, Salvia R, Bassi C. Pancreaticojejunostomy With Externalized Stent vs Pancreaticogastrostomy With Externalized Stent for Patients With High-Risk Pancreatic Anastomosis: A Single-Center, Phase 3, Randomized Clinical Trial. JAMA Surg. 2020 Apr 1;155(4):313-321. doi: 10.1001/jamasurg.2019.6035.

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2017
• Primary Completion (Actual): June 10, 2019
• Study Completion (Actual): July 10, 2019

Study Registration Dates

• First Submitted: November 9, 2016
• First Submitted That Met QC Criteria: July 6, 2017
• First Posted (Actual): July 11, 2017

Study Record Updates

• Last Update Posted (Actual): September 13, 2019
• Last Update Submitted That Met QC Criteria: September 12, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Stent; Pancreaticoduodenectomy; Pancreaticojejunostomy; Pancreaticogastrostomy; Transanastomotic drain
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathological Conditions, Anatomical; Pancreatic Diseases; Digestive System Fistula; Fistula; Pancreatic Fistula
• Other Study ID Numbers: PREP 1041CESC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Individual Participant Data will not be shared with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No