Routine White Test for Early Detection of Bile Leak in Elective Liver Resection (DELiveR Trial) (DELiveR)

Routine White Test for Early Detection of Bile Leak in Elective Liver Resection - A Study Protocol for a Randomized Controlled Trial at a Single High-Volume Hepatobiliary Center in Poland (DELiveR Trial)

Bile leakage is a clinically important complication following liver resection and is associated with increased postoperative morbidity, need for reintervention and prolonged hospitalisation. The White Test involves retrograde injection of a white lipid emulsion into the biliary tree to facilitate active identification of open bile ducts on the liver transection surface. However, the benefit and safety of its routine use across different types of liver resection remain uncertain.

The DELiveR Trial is a single-centre, prospective, randomised, parallel-group, participant- and outcome-assessor-blinded superiority trial. A total of 270 adults undergoing elective major or minor liver resection will be randomised in a 1:1 ratio to the White Test or a standardised white gauze assessment.

Final eligibility will be confirmed intraoperatively after confirmation of resectability, completion of liver parenchymal transection and haemostasis, and confirmation that a cystic duct or cystic duct stump can be safely approached for attempted cannulation. Randomisation will then be performed using a computer-generated sequence with permuted blocks and concealed allocation.

The White Test will involve slow, manual, low-pressure retrograde injection of 10-20 mL of SMOFlipid 5%, with temporary distal bile duct occlusion. Injection will be discontinued if abnormal resistance is encountered. Identified leakage sites will be clipped, ligated or sutured. The control group will undergo a standardised white gauze assessment according to a study-specific operating procedure.

All participants will have an intra-abdominal drain placed. Serum and drain-fluid bilirubin concentrations will be measured concurrently on postoperative day 3. Participants will be followed for 30 days.

The primary outcome is postoperative bile leakage within 30 days according to the International Study Group of Liver Surgery definition. The primary analysis will be conducted in the overall intention-to-treat population using logistic regression. Major versus minor hepatectomy will be evaluated only in exploratory subgroup and interaction analyses.

Secondary outcomes include clinically relevant grade B/C bile leakage, postoperative morbidity, major morbidity, reinterventions, intensive care unit use, hospital length of stay, readmission, mortality and potential intervention-related adverse events. An independent Data and Safety Monitoring Committee will periodically review safety data.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatectomy; Bile Leak; Liver Resection
• Intervention / Treatment: Procedure: Standard Gauze Test; Procedure: White Test

Detailed Description

Bile leakage remains a clinically important complication following liver resection and is associated with increased postoperative morbidity, need for radiological, endoscopic or surgical intervention, prolonged hospitalisation and increased healthcare costs. Effective intraoperative identification and closure of open bile ducts is therefore an important component of strategies intended to reduce postoperative bile leakage.

Conventional intraoperative methods, such as visual inspection of the liver transection surface and application of sterile white gauze, rely on passive identification of visible biliary outflow and may fail to identify small or occult leakage sites. The White Test is an active intraoperative bile leak assessment involving retrograde injection of a white lipid emulsion into the biliary tree. The resulting transient increase in intrabiliary pressure may enable visualisation of white emulsion at open bile ducts on the liver transection surface and permit immediate clipping, ligation or suturing.

Previous comparative studies and meta-analyses have suggested that the White Test may reduce postoperative bile leakage. However, the available evidence is heterogeneous, and the effectiveness and safety of routine White Test use across both major and minor liver resections have not been conclusively established.

The DELiveR Trial is a single-centre, prospective, randomised, parallel-group, participant- and outcome-assessor-blinded superiority trial. The trial will include adults undergoing elective major or minor liver resection, including anatomical and non-anatomical procedures.

Written informed consent will be obtained before surgery. Final eligibility will be confirmed intraoperatively after confirmation of resectability, completion of liver parenchymal transection and achievement of haemostasis, and confirmation that a cystic duct or cystic duct stump can be safely approached for attempted cannulation. Patients found to have unresectable disease, to require a procedure incompatible with the trial protocol or to have no safely accessible cystic duct or cystic duct stump will not undergo randomisation and will be recorded as screening failures.

Eligible participants will be randomised in a 1:1 ratio to the White Test or standardised white gauze assessment using a computer-generated sequence with permuted blocks. Allocation concealment will be maintained using sequentially numbered, opaque, sealed envelopes. The envelope will be opened only after final intraoperative eligibility has been documented and immediately before the assigned intraoperative bile leak assessment.

Participants and the investigator assessing the primary outcome will remain blinded to treatment allocation. The operating surgical team cannot be blinded after allocation because of the nature of the intervention. However, allocation will not be revealed until liver parenchymal transection and haemostasis have been completed. The blinded outcome assessor will review a predefined adjudication dataset from which treatment allocation and other allocation-revealing information will be withheld.

In the intervention group, the cystic duct or cystic duct stump will be cannulated after completion of liver parenchymal transection and haemostasis. The distal extrahepatic bile duct will be temporarily occluded below the cystic duct insertion. SMOFlipid 5% will then be administered retrogradely in a volume of 10-20 mL using slow, manual, low-pressure injection. Forceful injection will not be permitted, and injection will be immediately discontinued if abnormal resistance is encountered. The liver transection surface will be inspected for leakage of white emulsion. Identified leakage sites will be clipped, ligated or sutured, and the White Test may be repeated until no further leakage is observed. After completion of the test, the biliary tree will be flushed with 20-50 mL of sterile 0.9% sodium chloride solution.

If a participant is randomised to the White Test group but cannulation or completion of the test subsequently proves technically impossible, the participant will remain in the intervention group for the primary intention-to-treat analysis. The reason for technical non-completion and the procedure actually performed will be prospectively recorded.

In the control group, sterile white surgical gauze will be systematically applied to the liver transection surface after completion of liver parenchymal transection and haemostasis. The gauze and the transection surface will be inspected for visible biliary staining. Identified leakage sites will be clipped, ligated or sutured, and the assessment may be repeated until no further visible leakage is identified. The control assessment will be conducted according to a written study-specific standard operating procedure. Alternative active intraoperative bile leak tests will not be permitted as part of the study procedure in the control group. Any clinically necessary deviation will be prospectively recorded.

All participants will have an intra-abdominal drain placed at the liver resection site. Serum and drain-fluid total bilirubin concentrations will be measured concurrently on postoperative day 3 and may be repeated thereafter while the drain remains in place or when bile leakage is clinically suspected. Serum amylase and lipase concentrations will be measured on postoperative day 1. Postoperative pancreatitis, bile duct injury, cholangitis, allergic reactions and other potentially intervention-related adverse events will be prospectively recorded.

The primary outcome is postoperative bile leakage within 30 days, defined according to the International Study Group of Liver Surgery criteria as drain-fluid bilirubin concentration at least three times the concurrent serum bilirubin concentration on or after postoperative day 3, or the need for an intervention due to a biliary collection or biliary peritonitis.

Outcome assessment will be based on postoperative biochemical measurements, the clinical course during the index hospitalisation, imaging findings, postoperative interventions, readmissions and available medical documentation during the first 30 postoperative days. Telephone follow-up after discharge will be used to identify interval events but will not be used as the sole basis for excluding postoperative bile leakage.

The primary analysis will be conducted according to the intention-to-treat principle in the overall randomised population. Logistic regression will be used with treatment allocation as the independent variable. The treatment effect will be reported as an odds ratio with a 95% confidence interval and a two-sided p value. Event rates and the absolute risk difference will also be reported.

Major versus minor hepatectomy will be evaluated only in prespecified exploratory subgroup analyses. Potential heterogeneity of the treatment effect will be evaluated using a treatment-by-hepatectomy-type interaction term. A supplementary per-protocol analysis will include participants who received the allocated bile leak assessment according to the protocol.

The sample size calculation assumes postoperative bile leakage rates of 15% in the control group and 4.95% in the White Test group. With a two-sided significance level of 0.05, 80% statistical power, 1:1 allocation and a superiority design, 262 randomised participants are required. To allow for approximately 3% of participants with unavailable primary outcome data, the target sample size is 270 participants.

No formal interim efficacy analysis or formal statistical stopping boundary is planned. An independent Data and Safety Monitoring Committee will review accumulated safety data after every 50 randomised participants or at least every six months. The Committee may recommend continuation, modification, temporary suspension or termination of the trial if an unexpected safety signal is identified.

• Study Type: Interventional
• Enrollment (Estimated): 270
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Paweł Topolewski, MD; Phone Number: +48 22 599 25 45; Email: pawel.topolewski@wum.edu.pl
• Study Contact Backup: Name: Piotr Remiszewski, MD, PhD; Phone Number: +48 22 599 25 45; Email: piotr.remiszewski@wum.edu.pl

Study Locations

• Poland
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-097
      • Department of General, Transplant and Liver Surgery, Medical University of Warsaw
      • Contact: Piotr Remiszewski, MD, PhD; Phone Number: +48 22 599 25 45; Email: piotr.remiszewski@wum.edu.pl
      • Contact: Paweł Topolewski, MD; Phone Number: +48 22 599 2545; Email: pawel.topolewski@wum.edu.pl
      • Principal Investigator: Paweł Topolewski, MD
      • Principal Investigator: Piotr Remiszewski, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 years or older.
• Undergoing elective major or minor liver resection, including anatomical or non-anatomical liver resection.
• Technical eligibility for an attempted White Test, defined as the presence of an identifiable cystic duct or cystic duct stump that can be safely approached for attempted cannulation, as assessed intraoperatively after confirmation of resectability, completion of liver parenchymal transection and achievement of haemostasis.
• Written informed consent.

Exclusion Criteria:

• Intraoperative hepaticojejunostomy.
• Absence of a cystic duct or cystic duct stump that can be safely approached for attempted cannulation, as determined intraoperatively before randomisation.
• Unresectable disease identified intraoperatively.
• Known allergy to components of SMOFlipid 5%.
• Pregnancy or lactation.
• Emergency liver resection.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Arm - White Test; Participants allocated to this arm will undergo the White Test after completion of liver parenchymal transection and haemostasis. A cystic duct or cystic duct stump will be cannulated, and the distal extrahepatic bile duct will be temporarily occluded below the cystic duct insertion. SMOFlipid 5% will be administered retrogradely in a volume of 10-20 mL using slow, manual, low-pressure injection. Forceful injection will not be permitted, and injection will be discontinued if abnormal resistance is encountered. Identified leakage sites will be clipped, ligated or sutured, and the test may be repeated until no further leakage is observed. The biliary tree will subsequently be flushed with 20-50 mL of sterile 0.9% sodium chloride solution.	Procedure: White Test; The White Test is an active intraoperative bile leak assessment performed after completion of liver parenchymal transection and haemostasis. It involves slow, manual, low-pressure retrograde injection of 10-20 mL of SMOFlipid 5% through a cannulated cystic duct or cystic duct stump while the distal extrahepatic bile duct is temporarily occluded. The liver transection surface is inspected for leakage of white emulsion. Identified open bile ducts are clipped, ligated or sutured, and the test may be repeated until no further leakage is observed.
Active Comparator: Control Arm - Standard Gauze Test; Participants allocated to this arm will undergo a standardised white gauze assessment after completion of liver parenchymal transection and haemostasis. Sterile white surgical gauze will be systematically applied to the liver transection surface, and both the gauze and the transection surface will be inspected for visible biliary staining. Identified leakage sites will be clipped, ligated or sutured, and the assessment may be repeated until no further visible leakage is identified. The procedure will be conducted according to a written study-specific standard operating procedure. Alternative active intraoperative bile leak tests will not be permitted as part of the assigned control procedure.	Procedure: Standard Gauze Test; The standard gauze test is a conventional intraoperative method for bile leak detection. A sterile white surgical gauze is applied to the liver transection surface, and both the gauze and the surgical field are visually inspected for evidence of bile leakage. Detected leaks are managed by ligation or suturing, and the assessment may be repeated as needed according to standard surgical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative bile leakage according to the ISGLS definition	Number and proportion of participants with postoperative bile leakage within 30 days after liver resection, defined as drain-fluid bilirubin concentration at least three times the concurrent serum bilirubin concentration on or after postoperative day 3, or the need for an intervention due to a biliary collection or biliary peritonitis.	Within 30 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically relevant postoperative bile leakage	Number and proportion of participants with ISGLS grade B or C bile leakage.	Within 30 days after surgery
Severity of postoperative bile leakage	Number and proportion of participants classified as having no bile leakage or ISGLS grade A, B or C bile leakage.	Within 30 days after surgery
Overall postoperative morbidity	Number and proportion of participants experiencing at least one postoperative complication and the highest Clavien-Dindo grade recorded.	Within 30 days after surgery
Major postoperative morbidity	Number and proportion of participants experiencing a Clavien-Dindo grade III or higher complication.	Within 30 days after surgery.
Postoperative interventions	Number and proportion of participants requiring endoscopic, radiological or surgical intervention and the total number of such interventions.	Within 30 days after surgery.
All-cause mortality	Number and proportion of participants who die from any cause.	Within 30 days after surgery.
Potential intervention-related adverse events	Number and proportion of participants experiencing postoperative pancreatitis, bile duct injury, cholangitis, allergic reaction or another adverse event considered potentially related to cannulation or retrograde lipid-emulsion injection.	Within 30 days after surgery.
Hospital readmission	Number and proportion of participants readmitted to hospital for any reason.	Within 30 days after surgery.
Intensive care unit admission	Number and proportion of participants admitted to the intensive care unit after surgery.	Within 30 days after surgery.
Intensive care unit length of stay	Duration of intensive care unit stay measured in days.	From intensive care unit admission to intensive care unit discharge, assessed up to 30 days after surgery.
Hospital length of stay	Duration of the index hospitalisation measured in days from surgery to discharge.	Up to 30 days after surgery.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU admission and length of stay	Rate of intensive care unit (ICU) admission and duration of ICU stay measured in days.	Within 30 days after surgery
Hospital length of stay	Total duration of hospitalization measured in days from surgery to discharge.	Within 30 days after surgery

Collaborators and Investigators

• Sponsor: Medical University of Warsaw
• Investigators: Study Director: Piotr Remiszewski, MD, PhD, Medical University of Warsaw; Principal Investigator: Paweł Topolewski, MD, Medical University of Warsaw; Study Chair: Michał Grąt, MD, PhD,, Medical University of Warsaw

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): August 13, 2026
• Last Update Submitted That Met QC Criteria: August 11, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: liver resection; hepatectomy; bile ducts; white test
• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases
• Other Study ID Numbers: KB/47/2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the results reported in the primary trial publication will be available from the corresponding author upon reasonable request. The corresponding data dictionary and statistical analysis code will also be available. Data sharing will be subject to approval of a methodologically sound proposal, applicable data protection requirements and execution of an appropriate data-use agreement.
• IPD Sharing Time Frame: Data will be available beginning 12 months after publication of the primary trial results and will remain available for five years.
• IPD Sharing Access Criteria: Access will be considered for researchers who submit a methodologically sound proposal. Requests will be reviewed by the study investigators and sponsor, and access will require compliance with applicable data protection requirements and execution of a data-use agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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