Removable Intraductal Stenting in Duct-to-duct Biliary Reconstruction in Liver Transplantation

Study Overview
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Brief Summary
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Randomized controlled trial including 7 French transplantation centers. Pre-inclusion of the patients is made when enlisted for liver transplantation (LT). Definitive inclusion and randomization is performed during LT, for patients undergoing a duct-to-duct biliary anastomosis with a graft bile duct diameter smaller than 7mm. In the intraductal stent tube group, a custom-made segment of a T-tube is placed into the bile duct, and removed endoscopically four to six months postoperative. The surgical technique is available on a movie during randomization on the website. The primary endpoint is the occurrence of biliary complications, including biliary fistulae and strictures, during six months of follow-up. Secondary evaluation criteria are the incidence of complications related to the stent placement and its extraction by endoscopy. Discussion: Biliary complications following LT are significant causes of morbidity, retransplantation and eventually mortality. Although controversial, the use of a T-tube has been proven to be useless and even responsible for specific complications in many studies, including several randomized trials. However, several studies have identified a small bile duct diameter as a risk factor for biliary stenosis. A threshold of 7mm was found to be significantly associated to biliary stenosis. Our team published a preliminary study including 20 patients using a new technique of intraductal stenting. Only 4 complications were reported in the overall study population while no biliary complication occurred in the subgroup of patients who received a whole graft LT. Moreover, no technical failure and no procedure-related complications were noted before and during drain removal. Although intraductal stent tube in duct-to duct biliary anastomosis seems feasible and safe, a multicentric randomized controlled study is needed to validate it as a protective tool for biliary complications following LT.

Detailed Description
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Comparative, multicentric, prospective, randomized non-blinded, two-groups study. The follow-up is set at six months postoperative for a good screening of the majority of biliary complications. The inclusion period is set at 3.5 years, for total study duration of 4 years. The patients' inclusion will be made in 7 liver transplantation centers in France. Patients' inclusion will be performed in consultation at the moment of enlistment for LT, where they will be informed of the content, the benefits and risks of the study, and have to sign a written consent. Definitive inclusion will be performed in operating room, during LT, and depends on fulfilling of the following definitive inclusion criteria (see above). The randomization will be performed in operating room by the investigator and coordinated by the Clinical Research Unit of promoters' center (Saint Antoine Hospital, Paris), with a specific software accessible on the Internet. In the IST group, the surgeon will place the IST in the bile duct, which is a custom-made segment (2 cm) of a 8 French T-tube with no side holes. The stent is inserted in the biliary duct without suture fixation. In order to minimize bias and to homogenize the technique, a short technical explanatory movie will be realized by the promoter's team and distributed in each center. Each center will perform its habitual postoperative follow up. Clinical, biological, and radiological exhaustive data will be collected at Day 1, Day 7, Day 15, Month 1, Month 3, Month 6. A Magnetic Resonance Cholangiography (MRC) will be systematically performed at six months post LT. In the IST group, an endoscopic retrograde cholangio-pancreatography (ERCP) with sphincterotomy will be planned between the 4th and the 5th month post-transplantation, requiring a short stay in hospital, a general anesthesia, clinical and biological tests including plasmatic lipase dosage at Day 1. Every undesirable event will be immediately reported to the promoter for further investigation within its severity. Severe undesirable events will be previously defined.

Official Title
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Efficacy Of A Removable Intraductal Stent In Duct-To-Duct Biliary Reconstruction To Prevent Biliary Complications In Liver Transplantation: A Randomized Controlled Trial

Conditions
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Transplantation, Liver

Intervention / Treatment
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* Device: intraductal removable stent custom-made segment (2 cm)
* Procedure: stent extraction by ERCP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients eligible for a liver transplantation Patients' written informed consent signed Patient with social coverage (excepting AME) Exclusion criteria: Biliary reconstruction decided to be a hepaticojejunostomy for anatomical/biliary disease reason Non eligibility for liver transplantation: - Uncontrolled infectious process - Incompatible physical or mental state with the observance of the immunosuppressive drugs - Cardiopulmonary comorbidities severe / uncontrolled - Active alcohol intoxication or addiction - Pregnant or breastfeeding women (pregnancy test will be performed at baseline) Latex Allergy, polymer or rubber Patient participating in another interventional study about biliary disease

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intraductal stent (IST)<br>For intervention : intraductal removable stent In the IST group, the surgeon will place the IST in the bile duct, which is a custom-made segment (2 cm) of a 8 French T-tube. The stent is inserted in the biliary duct without suture fixation. In the IST group, an endoscopic retrograde cholangio-pancreatography (ERCP) with sphincterotomy will be planned between the 4th and the 6th month post-transplantation. | Device: intraductal removable stent custom-made segment (2 cm)<br>* : In the IST group, the surgeon will place the IST in the bile duct, which is a custom-made segment (2 cm) of a 8 French T-tube. The stent is inserted in the biliary duct without suture fixation. In order to minimize bias and to homogenize the technique, a short technical explanatory movie was realized by the promoter's team and edited on internet. In the IST group, an endoscopic retrograde cholangio-pancreatography (ERCP) with sphincterotomy will be planned between the 4th and the 5th month post-transplantation, requiring a short stay in hospital, a general anesthesia, clinical and biological tests including plasmatic lipase dosage at Day 1.<br>|
| Experimental: Without intraductal stent (no IST)<br>For intervention : stent extraction by endoscopic retrograde cholangio-pancreatography (ERCP) Each center will perform its habitual postoperative follow up. | Procedure: stent extraction by ERCP<br>* stent extraction by endoscopic retrograde cholangio-pancreatography<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of biliary strictures and biliary fistulae within six months post-transplantation. | A biliary leakage is defined by the presence of bile in the abdominal drainage, and/or an intra-abdominal collection with bilious content requiring drainage. A biliary stenosis is defined by a size discrepancy between the two sides of the bile duct anastomosis on specific imaging (MR cholangiography, ERCP), associated to an upstream bile tract distention, with a clinical and biological cholestasis, after excluding other cholestasis causes (rejection, viral reactivation). | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of specific complications related to the IST and its extraction by endoscopy | Secondary endpoints are the incidence of specific complications related to the IST and its extraction by endoscopy: cholangitis, stent migration, extraction difficulties, acute pancreatitis, digestive perforation, hemorrhage. | 6 months | 
| Graft survival | Incidence of graft loss, i.e. retransplantation rate | 6 months | 
| Patient survival | Incidence of patient death | 6 months |