Diagnostic Role of the "White Test" With Lipidic Solution in the Early Intraoperative Identification of Open Bile Ducts for the Prevention of Bile Leakage After Liver Resection (BiLe -Trial) (BiLe)

Diagnostic Role of the "White Test" With Lipidic Solution in the Early Intraoperative Identification of Open Bile Ducts for the Prevention of Bile Leakage After Liver Resection- A Randomized Controlled Multicentric Superiority Trial- The BiLe-Trial (Bile Leakage Trial)

Bile leakage (BL) is the most frequent complication after liver resection. This study is to investigate the role of intraoperative administration of SMOFlipid 20% (fat emulsion which allows intraoperative identification of open bile ducts at the liver resection surface when it is administered retrograde through the cystic duct) in terms of prevention of postoperative BL within 30 days after surgery.

Study Overview

• Status: Recruiting
• Conditions: Bile Leakage
• Intervention / Treatment: Drug: "white" test" (= the administration of SMOFlipid retrograde through the cystic duct)

Detailed Description

Bile leakage (BL) is the most frequent complication after liver resection leading to the need of interventional drainage, endoscopic retrograde cholangio pancreatography (ERCP) or even reoperation. Strategies leading to a reduction of the rate of this complication are valuable. SMOFlipid 20% is a fat emulsion which is primary indicated for parenteral nutrition. Because of its fatty content this solution is white. This allows the clear intraoperative identification of open bile ducts at the liver resection surface when it is administered retrograde through the cystic duct. Consequently, open bile ducts can be sutured preventing the postoperative development of BL. If the rate of bile leakages can be reduced, resources for interventions and relaparotomy will be saved. This study is to investigate intraoperative administration of SMOFlipid 20% in terms of prevention of BL within 30 days after surgery.

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Giulia Manzini, Dr. med.; Phone Number: +41-62-8389734; Email: giulia.manzini@ksa.ch

Study Locations

• Switzerland
  • Aarau, Switzerland, 5001
    • Recruiting
    • Department of Visceral Surgery, Cantonal Hospital of Aarau
    • Contact: Giulia Manzini, Dr. med.; Phone Number: 062-8389734; Email: giulia.manzini@ksa.ch
    • Principal Investigator: Giulia Manzini, Dr. med.
  • Basel, Switzerland, 4031
    • Recruiting
    • Clarunis Basel, Universitäres Bauchzentrum Basel
    • Contact: Otto Kollmar, Prof. Dr. med.; Phone Number: +41 61 777 73 20; Email: otto.kollmar@clarunis.ch
    • Principal Investigator: Otto Kollmar, Prof. Dr. med.
  • Lugano, Switzerland, 6900
    • Recruiting
    • Ospedale Regionale di Lugano
    • Contact: Alessandra Cristaudi, Dr. med.; Phone Number: 091 811 7208; Email: alessandra.cristaudi@eoc.ch
    • Principal Investigator: Alessandra Cristaudi, Dr. med.
  • Luzern, Switzerland, 6004
    • Recruiting
    • Kantonsspital Luzern
    • Contact: Andreas Scheiwiller, Dr. med.; Phone Number: 041 2054539; Email: andreas.scheiwiller@luks.ch
    • Principal Investigator: Andreas Scheiwiller, Dr. med.
  • St. Gallen, Switzerland, 9001
    • Recruiting
    • Kantonsspital St. Gallen
    • Contact: Ignazio Tarantino, PD Dr. med.; Phone Number: 071 4941312; Email: Ignazio.tarantino@kssg.ch
    • Principal Investigator: Ignazio Tarantino, PD Dr. med

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who will receive an anatomical resection of two or more liver segments for any reason with simultaneous cholecystectomy in elective Setting
• Patients who will receive an anatomical resection of two or more liver segments for any reason which already had a cholecystectomy if intraoperatively the cystic stump can be identified and opened
• Ability of subject to understand character and individual consequences of the clinical Trial
• Informed consent documented by signature

Exclusion Criteria:

• Previous cholecystectomy if intraoperative it is not possible to identify the cystic stump
• Intraoperative hepatico-jejunostomy
• Hypersensitivity to fish-, egg-, soybean or peanut protein or to any of the active ingredients or excipients
• Immunosuppression, pregnancy
• Emergency liver resection because of traumatic liver rupture
• Enrolment of the investigator, his/her family members, employees and other dependent persons

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Intervention (treatment); Open bile ducts are identified by visual control of the liver resection surface combined with the direct injection in the cystic stump of 20-40ml of SMOFlipid 20% Fresenius Kabi Canada Ltd.; authorization number: 57231 (Swissmedic). SMOFlipid is a white oily emulsion containing soya oil and medium chain triglycerides as main active components, normally used as parenteral nutrition as complement for essential fat acids supplementation. In this study the "white" test (= the administration of SMOFlipid retrograde through the cystic duct) is made by injection of one or two 20cc syringes full of lipidic solution (SMOFlipid 20%) in the cystic stump, directing the flow to the intrahepatic ducts. Residual fat emulsion is washed out from the biliary tract by a low pressure infusion of 20 to 50 ml of saline solution.	Drug: "white" test" (= the administration of SMOFlipid retrograde through the cystic duct); "white" test" (= the administration of SMOFlipid retrograde through the cystic duct)
No Intervention: Control Intervention; Open bile ducts are identified in the control group by visual control of the liver resection surface combined with the use of white gauzes (standard procedure)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of postoperative bile leakage	Comparison of the rate of postoperative bile leakage in the control and in the intervention group. This is a binary endpoint defined by the presence or absence of the bile leakage (yes or no). Bile leakage is defined as bilirubin concentration in the drain fluid at least 3 times the serum bilirubin concentration on or after postoperative day 3.	within 30 days postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of the bile leakage (Grade A, B or C according to the definition by Koch et al).	The severity of bile leakage is classified according to its impact on patients´ clinical management. Grade A bile leakage causes no change in patients' clinical management. A Grade B bile leakage requires active therapeutic intervention but is manageable without relaparotomy, whereas in Grade C bile leakage relaparotomy is required.	within 30 days postoperative
In-hospital mortality other than related to the bile leakage	In-hospital mortality other than related to the bile leakage	within 30 days postoperative
In-Hospital morbidity other than related to the bile leakage	In-Hospital morbidity other than related to the bile leakage	within 30 days postoperative
Endoscopic retrograde cholangio pancreatography (ERCP) (yes/no)	Endoscopic retrograde cholangio pancreatography (ERCP) (yes/no)	within 30 days postoperative
Percutaneous Transhepatic Cholangio Drainage (PTCD) (yes/no)	Percutaneous Transhepatic Cholangio Drainage (PTCD) (yes/no)	within 30 days postoperative
Interventional drainage (yes/no)	Interventional drainage (yes/no)	within 30 days postoperative
Re-operation (yes/no)	Re-operation (yes/no)	within 30 days postoperative
Intensive care unit (ICU) stay (in days)	Intensive care unit (ICU) stay (in days)	within 30 days postoperative
Total hospital stay (in days)	Total hospital stay (in days)	within 30 days postoperative

Collaborators and Investigators

• Sponsor: Giulia Manzini
• Investigators: Principal Investigator: Giulia Manzini, Dr. med., Cantonal Hospital of Aarau, Switzerland

Publications and helpful links

General Publications

• Cristaudi A, Tarantino I, Scheiwiller A, Wiencierz A, Majno-Hurst P, Schmied BM, Metzger J, Hartel M, Kremer M, Manzini G. Diagnostic role of the 'white test' with lipidic solution in the early intraoperative identification of open bile ducts for the prevention of bile leakage after liver resection: study protocol for a randomised controlled multicentric superiority trial (BiLe-Trial). BMJ Open. 2021 Jul 29;11(7):e049449. doi: 10.1136/bmjopen-2021-049449.

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: August 19, 2020
• First Submitted That Met QC Criteria: August 19, 2020
• First Posted (Actual): August 24, 2020

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 11, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Liver resection; SMOFlipid 20%; White Test
• Additional Relevant MeSH Terms: Pharmaceutical Solutions; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; SMOFlipid
• Other Study ID Numbers: 2020-02081; ex20Manzini

Drug and device information, study documents

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