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)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Bile Leakage

Intervention / Treatment
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* Drug: white test (= the administration of SMOFlipid retrograde through the cystic duct)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective randomized, controlled, observer and patient blinded multicentric (4 centres) superiority trial with 2 parallel study groups
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Intervention (treatment)<br>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)<br>* white test (= the administration of SMOFlipid retrograde through the cystic duct)<br>|
| No Intervention: Control Intervention<br>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?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver resection, SMOFlipid 20%, White Test