Flare Type Self-expandable Metal Stents (SEMS) vs Plastic Stent for the Treatment of Difficult Common Bile Duct Stone

Study Overview
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Brief Summary
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Migration of stones from the gallbladder to the common bile duct (CBD) facilitated by gallbladder contractions can be listed as a complication of gallstones disease. In the case of common bile duct stone (CBDs) migration, an endoscopic cholangiopancreatography (ERCP) should be offered for both symptomatic and asymptomatic patients fit for the procedure. An ERCP with an adequate endoscopic sphincterotomy obtains a complete biliary clearance in about 80-90% of the patients[5]. Whilst most cases are successfully treated with such first-line approaches, about 10-15% need alternative and/or adjunctive techniques to achieve bile duct clearance. These conditions are generally defined as difficult bile duct stones, a broad category of cases that encompasses very different scenarios. In the case of irretrievable CBDs, the European Society of Gastrointestinal Endoscopy (ESGE) recommends the endoscopic placement of a temporary biliary plastic stent to warrant biliary drainage. Since their introduction, fully covered self-expanding metal stents (FCSEMS) have rapidly been adopted for the treatment of benign biliary conditions such as strictures, leaks, or bleeding. In a recent retrospective study it has been shown that FCSEMS are useful in the approach of difficult lithiasis of CBD with no significant adverse events associated. Moreover, a promising FC-SEMS with a particular prosthesis design (flare type - Niti-S S-Type Taewoong) could be even more useful since it reduces the frequent complication of fully covered stents which is the migration of the prosthesis. However, prospective data on the effectiveness and on the adverse events rate on the use of SEMS for incomplete stone CBDs clearance are still lacking. Therefore, the investigators aim to estimate the incidence of adverse events, complete biliary clearance, and migration rate after 3-6 month from ERCP index (stent positioning), comparing plastic stents vs FC-SEMS (Niti-S flare type - Taewoong).

Detailed Description
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BACKGROUND The presence of gallstones is a very common condition worldwide, especially in developed countries where it is estimated to affect 10-15% of the adult population and accounts for a great part of total gastrointestinal-related healthcare expenditures[1]. Fortunately, only 10-25% of gallstones became symptomatic in their lifetime with an annual incidence of 2-3% per year [2, 3]. Moreover, the worldwide increase in obesity and in the prevalence of non-alcoholic fatty liver disease (NAFLD) , which represents a risk factor for gallstones, could contribute to the rising gallstone disease prevalence[4]. Migration of stones from the gallbladder to the common bile duct (CBD) facilitated by gallbladder contractions can be listed as a complication of gallstones disease. In the case of common bile duct stone (CBDs) migration, an endoscopic cholangiopancreatography (ERCP) should be offered for both symptomatic and asymptomatic patients fit for the procedure[1, 3]. An ERCP with an adequate endoscopic sphincterotomy obtains a complete biliary clearance in about 80-90% of the patients[5]. Whilst most cases are successfully treated with such first-line approaches, about 10-15% need alternative and/or adjunctive techniques to achieve bile duct clearance[1, 5]. These conditions are generally defined as difficult bile duct stones, a broad category of cases that encompasses very different scenarios, including large or multiple stones, peculiar stone shapes (e.g., barrel-shaped), stones located above a stricture or impacted, intrahepatic stones, altered distal bile duct (oblique, narrowed, sigmoid-shaped). In the case of irretrievable CBDs, the European Society of Gastrointestinal Endoscopy (ESGE) recommends the endoscopic placement of a temporary biliary plastic stent to warrant biliary drainage[1, 5, 6]. Numerous non-randomized studies, both prospective and retrospective, showed that an indwelling plastic stent may reduce the number and the size of CBDs[7-9], although the mechanism by which the endoprosthesis contributes to the clearance of CBD is unclear. Probably, the continuous friction between the CBDs and the stent contributes to producing mechanical stress that facilitates the disruption of the stones[10]. Available data showed that the biliary plastic stent had a success rate ranging from 44 to 96% for stone removal after the previous ERCP[11-14]. Since their introduction, fully covered self-expanding metal stents (FCSEMS) have rapidly been adopted for the treatment of benign biliary conditions such as strictures, leaks, or bleeding. In a recent retrospective study it has been shown that FCSEMS are useful in the approach of difficult lithiasis of CBD with no significant adverse events associated[9]. However, comparative prospective data between plastic and metal stents are still lacking. Theoretically, FC-SEMS could be more effective compared to the plastic stent in producing stress forces that facilitate the stone disintegration, but the quality of this evidence is still very low due to lack of data. Moreover, a promising FC-SEMS with a particular prosthesis design (flare type - Niti-S S-Type Taewoong) could be even more useful since it reduces the frequent complication of fully covered stents which is the migration of the prosthesis[15-17]. However, the majority of the data concerning SEMS migration rate are available for the treatment of benign biliary stricture, understandably, with a low rate of both distal and proximal migration[17]. However, prospective data on the effectiveness and on the adverse events rate on the use of SEMS for incomplete stone CBDs clearance are still lacking. A definitive biliary stenting is not recommended by ESGE guidelines, but it is warranted to completely remove the CBD stones during the second ERCP, if possible. AIM The investigators aim to estimate the incidence of adverse events, complete biliary clearance, and migration rate after 3-6 month from ERCP index (stent positioning) comparing plastic stents vs FC-SEMS (Niti-S flare type - Taewoong).

Official Title
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Flare Type Self-expandable Metal Stents (SEMS) vs Plastic Stent for the Treatment of Difficult Common Bile Duct Stone: a Randomized Post-marketing Multicenter Italian Study

Conditions
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Biliary Stones, Bile Duct Diseases, Bile Duct Obstruction

Intervention / Treatment
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* Device: Biliary drainage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 year-old with difficult common bile duct stones as defined by the current ESGE guidelines Patients with irretrievable biliary stone and incomplete biliary drainage Exclusion Criteria: Biliary malignant obstruction Other type of biliary benign or malignant stenosis

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention group<br>Intervention group (IG): Patients with flare type SEMS placement | Device: Biliary drainage<br>* Biliary drainage with FC-SEMS Niti-S FLARE TYPE<br>|
| Active Comparator: Control group (CG)<br>Control group (CG): Patients with plastic stent placement | Device: Biliary drainage<br>* Biliary drainage with FC-SEMS Niti-S FLARE TYPE<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | To estimate the incidence of adverse events, complete biliary clearance, and migration rate after 3-6 month from ERCP index (stent positioning), comparing plastic stents vs FC-SEMS (Niti-S flare type - Taewoong). | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Common bile duct lithiasis, Difficult lithiasis