Early Drain Removal Versus Standard Drain Management After Distal Pancreatectomy (Early-Dist)

NCT04609137 | Completed DMC

• 1 other identifier: Early-Dist
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Main indications for distal pancreatectomy (DP) are pancreatic body and tail tumors including ductal adenocarcinoma, neuroendocrine tumors, and cystic neoplasms. Despite a less invasive operation with lower morbidity compared to pancreatic head surgery, DP is burdened by the occurrence of clinically-relevant postoperative pancreatic fistula (CR-POPF) in a significant proportion of patients. Drain fluid amylase (DFA) on POD 1 (postoperative day 1) \> 2,000 U/L appears as the best performing threshold to predict the occurrence of CR-POPF after distal pancreatectomy. Although there is preliminary evidence that early drain removal in the subgroup of patients with DFA1 \< 2,000 U/L may reduce POPF, no prospective study has yet evaluated the impact of an early drain removal strategy compared to standard management. The research question of this study is to evaluate to what extent early postoperative drain removal according to a validated DFA1 impact on clinically-relevant POPF rate after distal pancreatectomy in comparison to standard drain management. The primary hypothesis is that, early drain removal will result in a reduced proportion of patients experiencing grade B-C POPF according to ISGPS definition. The proposed study is a two-group, assessor-blind, randomized trial. Participants will be randomly assigned with a 1:1 ratio into one of two groups: (1) standard drain management or (2) early drain removal strategy. In this study adults (\>18 years) patients with pancreatic body or tail diseases planned for distal pancreatectomy with or without splenectomy will be enrolled.The primary outcome is the POPF at 90 days after surgery, defined as grade B or C POPF according to ISGPS definition. Participants will be asked to complete some questionnaires in order to assess their general health status, and they will be evaluated at time of hospital admission, at 15 days, at 30 days after surgery (via telephone follow-up), and at 90 days after surgery (via telephone follow-up).

Conditions

Pancreas Disease; Complication,Postoperative; PROMs; Pancreatic Fistula

Keywords

pancreatic cancer

Outcome Measures

Primary Outcomes (1)

• Number of patients (n, %) developing a clinically-relevant pancreatic fistula (CR-POPF)

  The main (confirmatory) outcome of interest will be the occurrence of clinically-relevant pancreatic fistula at 90 days after surgery, defined as grade B or C POPF according to the 2016 ISGPS definition

  90 days after surgery

Secondary Outcomes (6)

• Time to functional recovery (TFR)

  7 days after surgery

• Comprehensive Complication Index (CCI)

  90 days after surgery

• Number of patients (n, %) developing a postoperative Surgical Site Infection (SSI)

  90 days after surgery

• Patient activity status - Duke Activity Status Index

  Pre-surgey, 15 days, 30 days, 90 days

• Generic health related quality of life - Patient Reported Outcome Measure Information System (PROMIS)-29+2 Profile version 2.1

  Pre-surgery, 15 days, 30 days, 90 days

Study Arms (2)

Early drain removal

EXPERIMENTAL

Participants will have an early drain removal (before postoperative day 3 (POD 3)) if specific conditions will be verified

Procedure: Early drain removal

Standard drain removal

ACTIVE COMPARATOR

Participants will receive the current standard of care at San Raffaele Hospital.

Procedure: Standard drain removal

Interventions

Early drain removal PROCEDURE

Patients randomized to the experimental group, will have an early drain removal if DFA on POD1 is lower than 2000 U/L and/or the drain fluid does not appear "sinister" (i.e. varying from dark brown to greenish fluid to milky water to clear "spring water" pancreatic juice like appearance) according to the clinical team. If DFA is greater than 2000 U/L, the drain will be maintained in place. If the sample on POD1 DFA is not available (e.g. drainage fluid is viscous and amylase value cannot be evaluated) or the sample could not be analyzed DFA will be evaluated on POD2, and drain removal will be considered if DFA is lower than 2000 U/L. If DFA on POD 3 is lower than 300 U/L, that is 3-fold the upper limit of normal serum amylase value, and/or the drain fluid does not appear "sinister" according to the clinical team, the drain will be removed. Otherwise, the drain will be kept in place and the patient will then follow standard postoperative drain management.

Early drain removal

Standard drain removal PROCEDURE

Patients randomized to this group will receive the current standard of care, thus the drain will be maintained at least until postoperative day 5. If DFA on POD 5 is lower than 3-fold the upper limit of normal serum amylase value, and/or the drain fluid does not appear "sinister" (i.e. varying from dark brown to greenish fluid to milky water to clear "spring water" pancreatic juice like appearance) according to the clinical team, the drain will be removed. If the drain is maintained in place beyond POD 5, it will be removed inhospital or after discharge when the daily amount is lower than 10 ml and there are no signs of ongoing infection

Standard drain removal

Eligibility Criteria

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

You may qualify if:

• Adults (\>18 years) with pancreatic body or tail diseases planned for distal pancreatectomy with or without splenectomy

You may not qualify if:

• patient receiving an operation other than distal pancreatectomy (non-resective sx, total pancreatectomy)
• concomitant celiac trunk resection (i.e. Appleby procedure)
• concomitant multivisceral resection (i.e. colonic, gastric or liver resection)

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

San Raffaele Hospital

Milan, 20132, Italy

Location

Related Publications (20)

• Lee MK 4th, Lewis RS, Strasberg SM, Hall BL, Allendorf JD, Beane JD, Behrman SW, Callery MP, Christein JD, Drebin JA, Epelboym I, He J, Pitt HA, Winslow E, Wolfgang C, Vollmer CM Jr. Defining the post-operative morbidity index for distal pancreatectomy. HPB (Oxford). 2014 Oct;16(10):915-23. doi: 10.1111/hpb.12293. Epub 2014 Jun 16.

  PMID: 24931404 BACKGROUND

• Miao Y, Lu Z, Yeo CJ, Vollmer CM Jr, Fernandez-Del Castillo C, Ghaneh P, Halloran CM, Kleeff J, de Rooij T, Werner J, Falconi M, Friess H, Zeh HJ, Izbicki JR, He J, Laukkarinen J, Dejong CH, Lillemoe KD, Conlon K, Takaori K, Gianotti L, Besselink MG, Del Chiaro M, Montorsi M, Tanaka M, Bockhorn M, Adham M, Olah A, Salvia R, Shrikhande SV, Hackert T, Shimosegawa T, Zureikat AH, Ceyhan GO, Peng Y, Wang G, Huang X, Dervenis C, Bassi C, Neoptolemos JP, Buchler MW; International Study Group of Pancreatic Surgery (ISGPS). Management of the pancreatic transection plane after left (distal) pancreatectomy: Expert consensus guidelines by the International Study Group of Pancreatic Surgery (ISGPS). Surgery. 2020 Jul;168(1):72-84. doi: 10.1016/j.surg.2020.02.018. Epub 2020 Apr 2.

  PMID: 32249092 BACKGROUND

• 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.

  PMID: 20622661 BACKGROUND

• McMillan MT, Vollmer CM Jr. Predictive factors for pancreatic fistula following pancreatectomy. Langenbecks Arch Surg. 2014 Oct;399(7):811-24. doi: 10.1007/s00423-014-1220-8. Epub 2014 Jun 25.

  PMID: 24962147 BACKGROUND

• Giglio MC, Spalding DR, Giakoustidis A, Zarzavadjian Le Bian A, Jiao LR, Habib NA, Pai M. Meta-analysis of drain amylase content on postoperative day 1 as a predictor of pancreatic fistula following pancreatic resection. Br J Surg. 2016 Mar;103(4):328-36. doi: 10.1002/bjs.10090. Epub 2016 Jan 21.

  PMID: 26791838 BACKGROUND

• McMillan MT, Christein JD, Callery MP, Behrman SW, Drebin JA, Hollis RH, Kent TS, Miller BC, Sprys MH, Watkins AA, Strasberg SM, Vollmer CM Jr. Comparing the burden of pancreatic fistulas after pancreatoduodenectomy and distal pancreatectomy. Surgery. 2016 Apr;159(4):1013-22. doi: 10.1016/j.surg.2015.10.028. Epub 2015 Dec 6.

  PMID: 26670325 BACKGROUND

• Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, Allen P, Andersson R, Asbun HJ, Besselink MG, Conlon K, Del Chiaro M, Falconi M, Fernandez-Cruz L, Fernandez-Del Castillo C, Fingerhut A, Friess H, Gouma DJ, Hackert T, Izbicki J, Lillemoe KD, Neoptolemos JP, Olah A, Schulick R, Shrikhande SV, Takada T, Takaori K, Traverso W, Vollmer CM, Wolfgang CL, Yeo CJ, Salvia R, Buchler M; International Study Group on Pancreatic Surgery (ISGPS). The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After. Surgery. 2017 Mar;161(3):584-591. doi: 10.1016/j.surg.2016.11.014. Epub 2016 Dec 28.

  PMID: 28040257 BACKGROUND

• Maggino L, Malleo G, Bassi C, Allegrini V, Beane JD, Beckman RM, Chen B, Dickson EJ, Drebin JA, Ecker BL, Fraker DL, House MG, Jamieson NB, Javed AA, Kowalsky SJ, Lee MK, McMillan MT, Roses RE, Salvia R, Valero V 3rd, Velu LKP, Wolfgang CL, Zureikat AH, Vollmer CM Jr. Identification of an Optimal Cut-off for Drain Fluid Amylase on Postoperative Day 1 for Predicting Clinically Relevant Fistula After Distal Pancreatectomy: A Multi-institutional Analysis and External Validation. Ann Surg. 2019 Feb;269(2):337-343. doi: 10.1097/SLA.0000000000002532.

  PMID: 28938266 BACKGROUND

• Daniel F, Tamim H, Hosni M, Ibrahim F, Mailhac A, Jamali F. Validation of day 1 drain fluid amylase level for prediction of clinically relevant fistula after distal pancreatectomy using the NSQIP database. Surgery. 2019 Feb;165(2):315-322. doi: 10.1016/j.surg.2018.07.030. Epub 2018 Nov 7.

  PMID: 30414706 BACKGROUND

• Seykora TF, Liu JB, Maggino L, Pitt HA, Vollmer CM Jr. Drain Management Following Distal Pancreatectomy: Characterization of Contemporary Practice and Impact of Early Removal. Ann Surg. 2020 Dec;272(6):1110-1117. doi: 10.1097/SLA.0000000000003205.

  PMID: 30943185 BACKGROUND

• Yang F, Jin C, Hao S, Fu D. Drain Contamination after Distal Pancreatectomy: Incidence, Risk Factors, and Association with Postoperative Pancreatic Fistula. J Gastrointest Surg. 2019 Dec;23(12):2449-2458. doi: 10.1007/s11605-019-04155-7. Epub 2019 Feb 27.

  PMID: 30815778 BACKGROUND

• Slankamenac K, Graf R, Barkun J, Puhan MA, Clavien PA. The comprehensive complication index: a novel continuous scale to measure surgical morbidity. Ann Surg. 2013 Jul;258(1):1-7. doi: 10.1097/SLA.0b013e318296c732.

  PMID: 23728278 BACKGROUND

• Horan TC, Gaynes RP, Martone WJ, Jarvis WR, Emori TG. CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC definitions of surgical wound infections. Infect Control Hosp Epidemiol. 1992 Oct;13(10):606-8. No abstract available.

  PMID: 1334988 BACKGROUND

• Wente MN, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, Izbicki JR, Neoptolemos JP, Padbury RT, Sarr MG, Traverso LW, Yeo CJ, Buchler MW. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery. 2007 Nov;142(5):761-8. doi: 10.1016/j.surg.2007.05.005.

  PMID: 17981197 BACKGROUND

• Wente MN, Veit JA, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, Izbicki JR, Neoptolemos JP, Padbury RT, Sarr MG, Yeo CJ, Buchler MW. Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery. 2007 Jul;142(1):20-5. doi: 10.1016/j.surg.2007.02.001.

  PMID: 17629996 BACKGROUND

• Hlatky MA, Boineau RE, Higginbotham MB, Lee KL, Mark DB, Califf RM, Cobb FR, Pryor DB. A brief self-administered questionnaire to determine functional capacity (the Duke Activity Status Index). Am J Cardiol. 1989 Sep 15;64(10):651-4. doi: 10.1016/0002-9149(89)90496-7.

  PMID: 2782256 BACKGROUND

• Alonso J, Permanyer-Miralda G, Cascant P, Brotons C, Prieto L, Soler-Soler J. Measuring functional status of chronic coronary patients. Reliability, validity and responsiveness to clinical change of the reduced version of the Duke Activity Status Index (DASI). Eur Heart J. 1997 Mar;18(3):414-9. doi: 10.1093/oxfordjournals.eurheartj.a015260.

  PMID: 9076377 BACKGROUND

• Carter R, Holiday DB, Grothues C, Nwasuruba C, Stocks J, Tiep B. Criterion validity of the Duke Activity Status Index for assessing functional capacity in patients with chronic obstructive pulmonary disease. J Cardiopulm Rehabil. 2002 Jul-Aug;22(4):298-308. doi: 10.1097/00008483-200207000-00014.

  PMID: 12202852 BACKGROUND

• Thompson EG, Gower ST, Beilby DS, Wallace S, Tomlinson S, Guest GD, Cade R, Serpell JS, Myles PS. Enhanced recovery after surgery program for elective abdominal surgery at three Victorian hospitals. Anaesth Intensive Care. 2012 May;40(3):450-9. doi: 10.1177/0310057X1204000310.

  PMID: 22577910 BACKGROUND

• Van Buren G 2nd, Bloomston M, Schmidt CR, Behrman SW, Zyromski NJ, Ball CG, Morgan KA, Hughes SJ, Karanicolas PJ, Allendorf JD, Vollmer CM Jr, Ly Q, Brown KM, Velanovich V, Winter JM, McElhany AL, Muscarella P 2nd, Schmidt CM, House MG, Dixon E, Dillhoff ME, Trevino JG, Hallet J, Coburn NSG, Nakeeb A, Behrns KE, Sasson AR, Ceppa EP, Abdel-Misih SRZ, Riall TS, Silberfein EJ, Ellison EC, Adams DB, Hsu C, Tran Cao HS, Mohammed S, Villafane-Ferriol N, Barakat O, Massarweh NN, Chai C, Mendez-Reyes JE, Fang A, Jo E, Mo Q, Fisher WE. A Prospective Randomized Multicenter Trial of Distal Pancreatectomy With and Without Routine Intraperitoneal Drainage. Ann Surg. 2017 Sep;266(3):421-431. doi: 10.1097/SLA.0000000000002375.

  PMID: 28692468 BACKGROUND

MeSH Terms

Conditions

Pancreatic Diseases; Postoperative Complications; Pancreatic Fistula; Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Digestive System Fistula; Fistula; Pathological Conditions, Anatomical; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Endocrine System Diseases

Study Officials

• Massimo Falconi, Professor

  Ospedale San Raffaele IRCCS

  PRINCIPAL INVESTIGATOR

• Stefano Partelli, Investigator

  Ospedale San Raffaele IRCCS

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 15, 2020
• First Posted: October 30, 2020
• Study Start: October 13, 2020
• Primary Completion: September 30, 2023
• Study Completion: October 30, 2023
• Last Updated: January 18, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)