Clinical and Economic Validation of the ISGPS Definition of PPAP

Postoperative Complications Clinical Trial

— ISGPS-PPAP  

Official title:

Clinical and Economic Validation of the International Study Group for Pancreatic Surgery (ISGPS) Definition of Postpancreatectomy Acute Pancreatitis (PPAP)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05680623
• Other study ID #: 3822CESC
• Status: Completed
• Start date: January 1, 2022
• Est. completion date: January 12, 2024

Study information

• Verified date: January 2024
• Source: Azienda Ospedaliera Universitaria Integrata Verona
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This prospective validation study aims to investigate the incidence of PPAP after pancreaticoduodenectomy (PD) by applying the ISGPS definition and grading system, to demonstrate its clinical impact by examining associated postoperative outcomes, and to validate its applicability through an economic assessment.

Description:

The study will be conducted at approximately 37 investigative sites in Europe, Asia, Oceania, and the United States. Only high volume centers for Pancreatic Surgery will be included in the study. All patients scheduled to receive elective pancreaticoduodenectomy (PD Kausch-Whipple or Longmire-Traverso) for all type of pancreatic disease (benign, malignant, or premalignant) will be enrolled. The study duration per subject will be up to 30 days after surgery or all the in-hospital lengths of stay. Preoperative care will follow institutional standards, according to each center involved. Surgical resection and reconstruction will be carried out according to the techniques adopted by each participating center. Both patients undergoing open and minimally invasive surgery can be considered eligible. Postoperative management will follow the institutional standards of each center. Serum amylase (total or the pancreatic isoform) and/or lipase activity will be systematically measured at least on postoperative days (POD) 1 and 2.Serum C-reactive protein (CRP) will be measured according to each institutional policy and reported once assessed from POD 1 to 3. Drain fluid amylase, or lipase activity will be checked according to the Institutional standards of each involved, and the values will be retrieved whether assessed from POD 1 to five. Radiological imaging will be performed in the postoperative course when clinically required, facing patients' clinical worsening, suspicious for abdominal complications.The severity of complications will be assessed according to the Clavien-Dindo (CD) classification system 32 . Readmission will be defined as a new hospital admission after discharge within 30 days from index surgery. Length of hospital stay is calculated from the day of surgery to discharge. Preoperative, intra-operative, and postoperative data will be recorded prospectively. The estimated study duration will be 15 months. Time for data analysis must be considered negligible. Patients' follow-up will last 30 days after surgery to catch any additional morbidity even after discharge from the hospital.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2900
• Est. completion date: January 12, 2024
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Scheduled for elective PD;
• Male and females = 18 years;
• Upfront or after neoadjuvant therapy surgery is allowed;
• The ability of the subject to understand the character and individual consequences of the clinical trial;
• Written informed consent.

Exclusion Criteria:

• Patients undergoing emergency surgery;
• Informed consent withdrawal;
• Inability to perform the resection for any reason;
• Total or distal pancreatectomy.

Related Conditions & MeSH terms

• Fistula
• Pancreatic Fistula
• Pancreaticoduodenectomy
• Pancreatitis
• Postoperative Complications
• Postoperative Pancreatic Fistula

Intervention

Diagnostic Test:
• PPAP diagnosis
Serum amylase (total or the pancreatic isoform) and/or lipase activity will be systematically measured at least on postoperative days 1 and 2. A CT with pancreas protocol iv contrast infusion will be performed in the postoperative course when clinically required, facing patients' clinical worsening, suspicious of abdominal complications.

Locations

Country	Name	City	State
Italy	Giovanni Marchegiani	Verona

Sponsors (33)

Lead Sponsor

Collaborator

Azienda Ospedaliera Universitaria Integrata Verona

Amsterdam UMC, location VUmc, Catholic University of the Sacred Heart, Christchurch Hospital, Flinders Medical Centre, Heidelberg University, Hospices Civils de Lyon, Hospital Miguel Servet, Humanitas Hospital, Italy, Indiana University Health, Kyoto University, Graduate School of Medicine, Kyushu University, Ludwig-Maximilians - University of Munich, Lund University, Massachusetts General Hospital, Mayo Clinic, Medical University of Vienna, New York University, Petz Aladar County Teaching Hospital, Royal Free Hospital NHS Foundation Trust, San Gerardo Hospital, Scientific Institute San Raffaele, Tata Memorial Hospital, Technical University of Munich, The First Affiliated Hospital with Nanjing Medical University, Thomas Jefferson University, UnitedHealth Group, Universitätsklinikum Hamburg-Eppendorf, University of Colorado, Denver, University of Dublin, Trinity College, University of Graz, University of Liverpool, University of Manchester

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Bannone E, Andrianello S, Marchegiani G, Masini G, Malleo G, Bassi C, Salvia R. Postoperative Acute Pancreatitis Following Pancreaticoduodenectomy: A Determinant of Fistula Potentially Driven by the Intraoperative Fluid Management. Ann Surg. 2018 Nov;268(5):815-822. doi: 10.1097/SLA.0000000000002900. — View Citation

Chen H, Wang W, Ying X, Deng X, Peng C, Cheng D, Shen B. Predictive factors for postoperative pancreatitis after pancreaticoduodenectomy: A single-center retrospective analysis of 1465 patients. Pancreatology. 2020 Mar;20(2):211-216. doi: 10.1016/j.pan.2019.11.014. Epub 2019 Nov 27. — View Citation

Loos M, Strobel O, Dietrich M, Mehrabi A, Ramouz A, Al-Saeedi M, Muller-Stich BP, Diener MK, Schneider M, Berchtold C, Feisst M, Hinz U, Mayer P, Giannakis A, Schneider D, Weigand MA, Buchler MW, Hackert T. Hyperamylasemia and acute pancreatitis after pancreatoduodenectomy: Two different entities. Surgery. 2021 Feb;169(2):369-376. doi: 10.1016/j.surg.2020.07.050. Epub 2020 Sep 25. — View Citation

Marchegiani G, Barreto SG, Bannone E, Sarr M, Vollmer CM, Connor S, Falconi M, Besselink MG, Salvia R, Wolfgang CL, Zyromski NJ, Yeo CJ, Adham M, Siriwardena AK, Takaori K, Hilal MA, Loos M, Probst P, Hackert T, Strobel O, Busch ORC, Lillemoe KD, Miao Y, Halloran CM, Werner J, Friess H, Izbicki JR, Bockhorn M, Vashist YK, Conlon K, Passas I, Gianotti L, Del Chiaro M, Schulick RD, Montorsi M, Olah A, Fusai GK, Serrablo A, Zerbi A, Fingerhut A, Andersson R, Padbury R, Dervenis C, Neoptolemos JP, Bassi C, Buchler MW, Shrikhande SV; International Study Group for Pancreatic Surgery. Postpancreatectomy Acute Pancreatitis (PPAP): Definition and Grading From the International Study Group for Pancreatic Surgery (ISGPS). Ann Surg. 2022 Apr 1;275(4):663-672. doi: 10.1097/SLA.0000000000005226. — View Citation

Partelli S, Tamburrino D, Andreasi V, Mazzocato S, Crippa S, Perretti E, Belfiori G, Marmorale C, Balzano G, Falconi M. Implications of increased serum amylase after pancreaticoduodenectomy: toward a better definition of clinically relevant postoperative acute pancreatitis. HPB (Oxford). 2020 Nov;22(11):1645-1653. doi: 10.1016/j.hpb.2020.03.010. Epub 2020 Apr 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of PPAP	The incidence of PPAP after pancreaticoduodenectomy (PD) by applying the ISGPS definition and grading system.	30 postoperative days
Primary	The incidence of unplanned ICU admissions and hospital readmission in the PPAP group compared to the non-PPAP one.	Only an unplanned need for intensive care will be defined as intensive care unit (ICU) stay. Readmission will be defined as a new hospital admission after discharge within 30 days from index surgery.	30 postoperative days
Primary	The difference in length of hospital stay between the PPAP and the non-PPAP group	Length of hospital stay is calculated from the day of surgery to discharge.	up to hospital discharge, an average of 30 postoperative days
Primary	The difference in hospital costs among the different grades of severity according to the ISGPS grading system22: no PPAP or POH, POH, PPAP grade B, and PPAP grade C groups.	Total hospital costs will comprise the cost of the index admission and every surgery-related readmission within 30 days from the index surgery. Costs will be inflation-adjusted using the standardized national consumer price index and normalized to adjust the variability inherent to different health systems and institutions.	30 postoperative days
Secondary	Correlation between postoperative serum amylase/serum lipase activity (U/L) and radiologic feature consistent with PPAP retrieved at postoperative imaging.	Serum amylase and/or lipase activity will be systematically measured on postoperative days (POD) 1 and 2.; Radiological imaging will be performed in the postoperative course when clinically required, facing the patient's clinical worsening, and suspicious of abdominal complications.	30 postoperative days
Secondary	Incidence and descriptive analysis of radiological features consistent with PAPP at postoperative imaging retrieved at different time points.	The radiologic evaluation will include the pancreas enlargement, pancreas enhancement, pancreatic necrosis and percentage, peripancreatic collections, characteristics, and their location, haemorrhage and pseudoaneurysm, ascites, thrombosis, main pancreatic duct diameter (mm), POD imaging (days).	30 postoperative days
Secondary	Incidence and severity of postoperative morbidity.	Postoperative morbidity will be defined according to ISGPS definitions of postoperative pancreatic fistula, delayed gastric emptying, post-pancreatectomy hemorrhage, and chyle leak. Bile leakage as defined by ISGLS. Acute kidney injury will be determined according to 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The severity of complications will be assessed according to the Clavien-Dindo classification system.	30 postoperative days
Secondary	Incidence of postoperative mortality.	Mortality will be defined as postoperative death recorded out to the point of 30-days postoperatively. Beyond these time limits, the mortality, possibly related to PPAP, will be considered and discussed in each case.	30 postoperative days