Bile LeakagePhase 3BiLeNCT04523701
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)
A Phase 3 study testing "white" test" (= the administration of SMOFlipid retrograde through the cystic duct) in people with Bile Leakage, run by Giulia Manzini at 5 sites in Switzerland.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bile Leakage
- What is being tested?
- "white" test" (= the administration of SMOFlipid retrograde through the cystic duct)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 5 sitesSwitzerland
- Study dates
- 25 Mar 2021to Dec 2025
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Switzerland5 sites, 5 recruiting
- Recruiting
Department of Visceral Surgery, Cantonal Hospital of Aarau
Aarau, 5001
Giulia Manzini, Dr. med., 062-8389734, giulia.manzini@ksa.ch
Giulia Manzini, Dr. med.
- Recruiting
Clarunis Basel, Universitäres Bauchzentrum Basel
Basel, 4031
Otto Kollmar, Prof. Dr. med., +41 61 777 73 20, otto.kollmar@clarunis.ch
Otto Kollmar, Prof. Dr. med.
- Recruiting
Kantonsspital Luzern
Lucerne, 6004
Andreas Scheiwiller, Dr. med., 041 2054539, andreas.scheiwiller@luks.ch
Andreas Scheiwiller, Dr. med.
- Recruiting
Ospedale Regionale di Lugano
Lugano, 6900
Alessandra Cristaudi, Dr. med., 091 811 7208, alessandra.cristaudi@eoc.ch
Alessandra Cristaudi, Dr. med.
- Recruiting
Kantonsspital St. Gallen
Sankt Gallen, 9001
Ignazio Tarantino, PD Dr. med., 071 4941312, Ignazio.tarantino@kssg.ch
Ignazio Tarantino, PD Dr. med
About this study
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)
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.
Read the 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.
- Conditions
- Bile Leakage
- Being tested
- "white" test" (= the administration of SMOFlipid retrograde through the cystic duct)
- Keywords
- Liver resection, SMOFlipid 20%, White Test
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
"white" test" (= the administration of SMOFlipid retrograde through the cystic duct)Drug
"white" test" (= the administration of SMOFlipid retrograde through the cystic duct)
| Study group | Role | What they receive |
|---|---|---|
| Experimental Intervention (treatment) | Experimental | 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. Receives: Drug: "white" test" (= the administration of SMOFlipid retrograde through the cystic duct) |
| Control Intervention | No 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: within 30 days postoperative
Secondary outcomes (9)
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.
Measured: within 30 days postoperative
In-hospital mortality other than related to the bile leakage
In-hospital mortality other than related to the bile leakage
Measured: within 30 days postoperative
In-Hospital morbidity other than related to the bile leakage
In-Hospital morbidity other than related to the bile leakage
Measured: within 30 days postoperative
Endoscopic retrograde cholangio pancreatography (ERCP) (yes/no)
Endoscopic retrograde cholangio pancreatography (ERCP) (yes/no)
Measured: within 30 days postoperative
Percutaneous Transhepatic Cholangio Drainage (PTCD) (yes/no)
Percutaneous Transhepatic Cholangio Drainage (PTCD) (yes/no)
Measured: within 30 days postoperative
Interventional drainage (yes/no)
Interventional drainage (yes/no)
Measured: within 30 days postoperative
Re-operation (yes/no)
Re-operation (yes/no)
Measured: within 30 days postoperative
Intensive care unit (ICU) stay (in days)
Intensive care unit (ICU) stay (in days)
Measured: within 30 days postoperative
Total hospital stay (in days)
Total hospital stay (in days)
Measured: within 30 days postoperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2020
- Study start25 Mar 2021
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bile LeakageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective randomized, controlled, observer and patient blinded multicentric (4 centres) superiority trial with 2 parallel study groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 210 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Giulia Manzini
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Giulia Manzini, Kantonsspital Aarau
- Investigators
- Giulia Manzini, Dr. med., Principal investigator, Cantonal Hospital of Aarau, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04523701
- Sponsor's protocol ID
- 2020-02081; ex20Manzini
- Acronym
- BiLe
- Status last verified
- Mar 2025
- First submitted
- 19 Aug 2020
- Last updated
- 14 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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.
PubMed 34326053
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04523701
- Acronym / sponsor ID
- BiLe / 2020-02081; ex20Manzini
- Conditions
- Bile Leakage
- Keywords
- Liver resection, SMOFlipid 20%, White Test
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 210 participants (estimated)
- Lead sponsor
- Giulia ManziniUniversity, hospital or other
- Study start
- 25 Mar 2021 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 24 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- Prospective randomized, controlled, observer and patient blinded multicentric (4 centres) superiority trial with 2 parallel study groups
| Arm | Type | Receives |
|---|---|---|
| Experimental Intervention (treatment) | Experimental | Drug: "white" test" (= the administration of SMOFlipid retrograde through the cystic duct)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. |
| Control Intervention | No 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| "white" test" (= the administration of SMOFlipid retrograde through the cystic duct)"white" test" (= the administration of SMOFlipid retrograde through the cystic duct) | Drug | Experimental Intervention (treatment) |
Primary outcome
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.
9 secondary outcomes
Severity of the bile leakage (Grade A, B or C according to the definition by Koch et al).
Time frame: within 30 days postoperative
In-hospital mortality other than related to the bile leakage
Time frame: within 30 days postoperative
In-Hospital morbidity other than related to the bile leakage
Time frame: within 30 days postoperative
Endoscopic retrograde cholangio pancreatography (ERCP) (yes/no)
Time frame: within 30 days postoperative
Percutaneous Transhepatic Cholangio Drainage (PTCD) (yes/no)
Time frame: within 30 days postoperative
Interventional drainage (yes/no)
Time frame: within 30 days postoperative
Re-operation (yes/no)
Time frame: within 30 days postoperative
Intensive care unit (ICU) stay (in days)
Time frame: within 30 days postoperative
Total hospital stay (in days)
Time frame: within 30 days postoperative
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2025.
- Derived from this study: PubMed 34326053Cristaudi 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Giulia Manzini, Dr. med. principal investigator
Cantonal Hospital of Aarau, Switzerland
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing "white" test" (= the administration of SMOFlipid retrograde through the cystic duct) in people with Bile Leakage, run by Giulia Manzini at 5 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Giulia Manzini, Dr. med. (+41-62-8389734, giulia.manzini@ksa.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
rate of postoperative bile leakage (time frame: within 30 days postoperative). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04523701, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2025.