Clinical trial NCT05680623: Clinical and Economic Validation of the ISGPS Definition of PPAP
Official title: Clinical and Economic Validation of the International Study Group for Pancreatic Surgery (ISGPS) Definition of Postpancreatectomy Acute Pancreatitis (PPAP)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Postoperative Acute Pancreatitis
Pancreaticoduodenectomy
Postoperative Pancreatic Fistula
Postoperative Complications
Keywords: pancreatitis
hyperamylasemia
pancreatoduodenectomy
postoperative complications
pancreatic fistula
Lead sponsor: Azienda Ospedaliera Universitaria Integrata Verona
Sponsor class: OTHER
Collaborators: name: Heidelberg University
name: Catholic University of the Sacred Heart
name: Hospices Civils de Lyon
name: Lund University
name: Flinders Medical Centre
name: Amsterdam UMC, location VUmc
name: University of Dublin, Trinity College
name: Christchurch Hospital
name: University of Colorado, Denver
name: Scientific Institute San Raffaele
name: University of Graz
name: Technical University of Munich
name: Royal Free Hospital NHS Foundation Trust
name: San Gerardo Hospital
name: University of Liverpool
name: Universitätsklinikum Hamburg-Eppendorf
name: Massachusetts General Hospital
name: Kyushu University
name: The First Affiliated Hospital with Nanjing Medical University
name: Petz Aladar County Teaching Hospital
name: Mayo Clinic
name: Hospital Miguel Servet
name: Tata Memorial Hospital
name: Medical University of Vienna
name: Kyoto University, Graduate School of Medicine
name: UnitedHealth Group
name: Ludwig-Maximilians - University of Munich
name: Thomas Jefferson University
name: Humanitas Hospital, Italy
name: Indiana University Health
name: University of Manchester
name: New York University
First posted: 2023-01-11
Enrollment: 2900
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 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.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The incidence of PPAP
timeFrame: 30 postoperative days
measure: The incidence of unplanned ICU admissions and hospital readmission in the PPAP group compared to the non-PPAP one.
timeFrame: 30 postoperative days
measure: The difference in length of hospital stay between the PPAP and the non-PPAP group
timeFrame: up to hospital discharge, an average of 30 postoperative days
measure: 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.
timeFrame: 30 postoperative days
Secondary outcomes:
measure: Correlation between postoperative serum amylase/serum lipase activity (U/L) and radiologic feature consistent with PPAP retrieved at postoperative imaging.
timeFrame: 30 postoperative days
measure: Incidence and descriptive analysis of radiological features consistent with PAPP at postoperative imaging retrieved at different time points.
timeFrame: 30 postoperative days
measure: Incidence and severity of postoperative morbidity.
timeFrame: 30 postoperative days
measure: Incidence of postoperative mortality.
timeFrame: 30 postoperative days
Other outcomes:
Locations:
city: Verona
country: Italy
facility: Giovanni Marchegiani
Study officials:
affiliation: Azienda Ospedaliera Universitaria Integrata di Verona
name: Giovanni Marchegiani
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
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.
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.