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)

• ClinicalTrials.gov Identifier: NCT04523701
• Recruitment Status: Recruiting
• First Posted: August 24, 2020
• Last Update Posted: October 12, 2023
• Sponsor: Giulia Manzini
• Information provided by (Responsible Party): Giulia Manzini, Kantonsspital Aarau

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Bile Leakage	Drug: "white" test" (= the administration of SMOFlipid retrograde through the cystic duct)	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 210 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Prospective randomized, controlled, observer and patient blinded multicentric (4 centres) superiority trial with 2 parallel study groups
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Masking Description: Patients, care providers and outcome assessors are blinded, the surgical team is not blinded.
• Primary Purpose: Prevention
• Official Title: 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)
• Actual Study Start Date: March 25, 2021
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: December 2025

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. rate of postoperative bile leakage [ Time Frame: within 30 days postoperative ]
   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.

Secondary Outcome Measures :

1. Severity of the bile leakage (Grade A, B or C according to the definition by Koch et al). [ Time Frame: within 30 days postoperative ]
   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.
2. In-hospital mortality other than related to the bile leakage [ Time Frame: within 30 days postoperative ]
   In-hospital mortality other than related to the bile leakage
3. In-Hospital morbidity other than related to the bile leakage [ Time Frame: within 30 days postoperative ]
   In-Hospital morbidity other than related to the bile leakage
4. Endoscopic retrograde cholangio pancreatography (ERCP) (yes/no) [ Time Frame: within 30 days postoperative ]
   Endoscopic retrograde cholangio pancreatography (ERCP) (yes/no)
5. Percutaneous Transhepatic Cholangio Drainage (PTCD) (yes/no) [ Time Frame: within 30 days postoperative ]
   Percutaneous Transhepatic Cholangio Drainage (PTCD) (yes/no)
6. Interventional drainage (yes/no) [ Time Frame: within 30 days postoperative ]
   Interventional drainage (yes/no)
7. Re-operation (yes/no) [ Time Frame: within 30 days postoperative ]
   Re-operation (yes/no)
8. Intensive care unit (ICU) stay (in days) [ Time Frame: within 30 days postoperative ]
   Intensive care unit (ICU) stay (in days)
9. Total hospital stay (in days) [ Time Frame: within 30 days postoperative ]
   Total hospital stay (in days)

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Giulia Manzini, Dr. med.; +41-62-8389734; giulia.manzini@ksa.ch

Locations

Switzerland

Department of Visceral Surgery, Cantonal Hospital of Aarau; Recruiting

Aarau, Switzerland, 5001

Contact: Giulia Manzini, Dr. med. 062-8389734 giulia.manzini@ksa.ch

Principal Investigator: Giulia Manzini, Dr. med.

Clarunis Basel, Universitäres Bauchzentrum Basel; Recruiting

Basel, Switzerland, 4031

Contact: Otto Kollmar, Prof. Dr. med. +41 61 777 73 20 otto.kollmar@clarunis.ch

Principal Investigator: Otto Kollmar, Prof. Dr. med.

Ospedale Regionale di Lugano; Recruiting

Lugano, Switzerland, 6900

Contact: Alessandra Cristaudi, Dr. med. 091 811 7208 alessandra.cristaudi@eoc.ch

Principal Investigator: Alessandra Cristaudi, Dr. med.

Kantonsspital Luzern; Recruiting

Luzern, Switzerland, 6004

Contact: Andreas Scheiwiller, Dr. med. 041 2054539 andreas.scheiwiller@luks.ch

Principal Investigator: Andreas Scheiwiller, Dr. med.

Kantonsspital St. Gallen; Recruiting

St. Gallen, Switzerland, 9001

Contact: Ignazio Tarantino, PD Dr. med. 071 4941312 Ignazio.tarantino@kssg.ch

Principal Investigator: Ignazio Tarantino, PD Dr. med

Sponsors and Collaborators

Giulia Manzini

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Giulia Manzini, Dr. med., Senior physician, Department of Visceral Surgery, Kantonsspital Aarau
• ClinicalTrials.gov Identifier: NCT04523701
• Other Study ID Numbers: 2020-02081; ex20Manzini
• First Posted: August 24, 2020
• Last Update Posted: October 12, 2023
• Last Verified: October 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Giulia Manzini, Kantonsspital Aarau:

Liver resection; SMOFlipid 20%; White Test

Additional relevant MeSH terms:

SMOFlipid; Fat Emulsions, Intravenous; Parenteral Nutrition Solutions; Pharmaceutical Solutions