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)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 270
- 试验地点
- 1
- 主要终点
- Postoperative bile leakage according to the ISGLS definition
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
Participants will remain blinded to treatment allocation throughout the 30-day follow-up period. The operating surgical team cannot be blinded after allocation because of the nature of the intervention. The primary outcome will be assessed by an investigator who was not involved in the index surgical procedure and who will remain blinded to treatment allocation. The assessor will review a predefined adjudication dataset from which allocation-revealing information will be withheld.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Standard Gauze Test (Procedure)
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.
干预措施: White Test (Procedure)
结局指标
主要结局
Postoperative bile leakage according to the ISGLS definition
时间窗: Within 30 days after surgery
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.
次要结局
- Clinically relevant postoperative bile leakage(Within 30 days after surgery)
- Severity of postoperative bile leakage(Within 30 days after surgery)
- Overall postoperative morbidity(Within 30 days after surgery)
- Major postoperative morbidity(Within 30 days after surgery.)
- Postoperative interventions(Within 30 days after surgery.)
- All-cause mortality(Within 30 days after surgery.)
- Potential intervention-related adverse events(Within 30 days after surgery.)
- Hospital readmission(Within 30 days after surgery.)
- Intensive care unit admission(Within 30 days after surgery.)
- Intensive care unit length of stay(From intensive care unit admission to intensive care unit discharge, assessed up to 30 days after surgery.)
- Hospital length of stay(Up to 30 days after surgery.)