Primary EUS-GBD in Patients With Unresectable Malignant Biliary Obstruction and Cystic Duct Orifice Involvement.

Study Overview
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Brief Summary
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to determine if primary prophylaxis with Endoscopic Ultrasound-Gallbladder Drainage (EUS-GBD) in unresectable cancer patients with the orifice of the cystic duct (OCD) involvement is superior to conservative management (Non EUS-guided gallbladder drainage).

Detailed Description
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Endoscopic biliary drainage with a self-expandable metal stent (SEMS) is an accepted form of palliative therapy for distal malignant biliary obstruction (MBO); it is a low invasive procedure with a long-term patency. Covered SEMSs have a longer patency than uncovered SEMSs in patients with MBO, because covered SEMSs can prevent tumor ingrowth. However, complications of covered SEMSs include stent occlusion, migration, kinking, non-occlusion cholangitis, liver abscess, pancreatitis and cholecystitis. Nonsurgical decompression of the gallbladder is urgently needs to prevent sepsis, perforation and death in patients with acute cholecystitis. Several risk factors of cholecystitis after SEMS placement for distal MBO have been reported: however, tumor involvement to the orifice of the cystic duct (OCD) is the major predictive factor for cholecystitis after endoscopic SEMSs placement for distal MBO palliative treatment . Acute cholecystitis related to SEMSs deployment was evaluated in 2009, by using endoscopic trans-papillary gallbladder drainage (TPGBD) in 11 individuals in whom SEMSs covered the OCD. None episode of cholecystitis was reported, however TPGBD is a difficult technique with a high rate of stent dislodgement and reintervention needed. EUS-GBD by using a lumen apposing metal stent have been proposed, but only for acute cholecystitis treatment or symptomatic gallbladder hydrops, never as a prophylactic technique. The aim of this study if to determine if primary prophylaxis EUS-GBD in patients with distal malignant biliary obstruction and the OCD involvement is superior than conservative management. Also, a cost-effectiveness analysis will be done in both arm groups. This would be the first trial to study the effect of prophylactic EUS-GBD prior SEMSs deployment in patients with distal malignant biliary obstruction.

Official Title
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Prophylactic Endoscopic Ultrasound Gallbladder Drainage (EUS-GBD) in Patients With Unresectable Malignant Biliary Obstruction and Cystic Duct Orifice Involvement.

Conditions
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Acute Cholecystitis

Intervention / Treatment
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* Procedure: EUS-guided gallbladder drainage
* Procedure: Non EUS-guided gallbladder drainage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Above 18 years old. Obtained written consent for procedures Unresectable malignant biliary obstruction diagnosed by Endoscopic Ultrasound and confirmed by confocal laser endomicroscopy (CLE) during cholangioscopy and histopathology. Tumor involvement to the orifice of the cystic duct. Self-expandable metallic plastic stent deployment as palliative therapy for distal biliary obstruction. Exclusion Criteria: Under 18 years old. Refuse to sign written informed consent. Pregnancy Previous cholecystectomy Acute cholecystitis prior enrollment Severe ascites that increases the distance between gastric or duodenal and gallbladder walls. Large vessel between the gallbladder and gastric-duodenal wall. Coagulopathy Intrahepatic cholangiocarcinoma Previous gallbladder drainage by percutaneous or endoscopic techniques.

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 |
| --- | --- |
| Other: EUS-guided gallbladder drainage<br>In one arm, Endoscopic Ultrasound-Gallbladder Drainage (EUS-GBD) will be performed by using a 3,8 mm therapeutic echoendoscope and a lumen apposing metal stent ( Hot AXIOS™ Stent and Electrocautery Enhanced Delivered System; Boston Scientific Corporation, Natick, MA, USA) after conventional biliary drainage with self-expandable metallic stents during endoscopic retrograde cholangiopancreatography (ERCP). All procedures will be performed under general anesthesia. | Procedure: EUS-guided gallbladder drainage<br>* During ERCP evaluation a self-expandable metallic stent will be deployed in the common biliary duct of the patients enrolled in both arms of the present study. A prophylaxis gallbladder drainage will be done using a 3.8 mm working-channel linear-array therapeutic echoendoscope (EG3870UTK;Pentax, Hamburg, Germany) attached to an ultrasound console (Avius Hitachi, Tokyo, Japan) within a transgastric and/or transduodenal approaches to the gallbladder puncture followed by placement of a lumen apposing stent (LAMS) (AXIOS; Xlumena Inc, CA, USA) with a 10 mm luminal diameter and a dumbbell-shaped flanges to bring together the 2 walls in apposition. These feature of the Axios decrease the risk for bile leak, stent migration, and stent occlusion.<br>Procedure: Non EUS-guided gallbladder drainage<br>* During ERCP evaluation a self-expandable metallic stent will be deployed in the common biliary duct of the patients enrolled in both arms of the present study. If the patient had an acute cholecystitis will be sent to surgery and be considered as a Non EUS-guided gallbladder drainage<br>|
| Other: Non EUS-guided gallbladder drainage<br>In the other arm, patients will undergo conventional biliary drainage with self-expandable metallic stent placement during ERCP evaluation without prophylactic EUS-GBD and will be considered as a Non EUS-guided gallbladder drainage. All procedures will be performed under general anesthesia. | Procedure: Non EUS-guided gallbladder drainage<br>* During ERCP evaluation a self-expandable metallic stent will be deployed in the common biliary duct of the patients enrolled in both arms of the present study. If the patient had an acute cholecystitis will be sent to surgery and be considered as a Non EUS-guided gallbladder drainage<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocurrence of acute cholecystitis | • Occurrence of acute cholecystitis according to Tokyo guidelines 2013: Clinical symptoms showing right upper or epigastric pain or tenderness, signs of systematic inflammation (fever, elevated white blood cell count, and C-reactive protein), or positive findings on abdominal ultrasonography (US) or computed tomography (CT). | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Technical success rate: EUS-GBD | as the ability of access and drain the gallbladder by placement of a drainage stent: lumen apposing metal stent ( Hot AXIOS™ Stent and Electrocautery Enhanced Delivered System; Boston Scientific Corporation, Natick, MA, USA). | from the beginning of the EUS-GBD procedure and 10 minutes after LAMS placement. | 
| Clinical success rate: | non-occurrence of acute cholecystitis during follow up OR successful SEMS placement with biliary decompression and relief of jaundice pruritus. | since enrollment until 30-days follow up. | 
| adverse events | any procedure-related adverse event (anesthesia, EUS-GBD, ERCP). | from the beginning of the procedure until 30 days. | 
| presence of pus during EUS-GBD | endoscopic visualization of pus after EUS-GBD. Yes or no. | immediate after EUS-GBD. | 
| Duration of the lumen apposing stent patency in the EUS-GBD arm study | Duration of the lumen apposing stent patency in the EUS-GBD arm study | the interval (days) between the time of stent placement and that of stent malfunction or patient death, whichever came first, assessed up to 12 months. | 
| Need for gallbladder re-intervention. | on EUS-GBD patients arm, need for a new gallbladder drainage (surgical or percutaneous) due to the occurrence of acute cholecystitis. | from the end of the procedure until the date of first documented episode of acute cholecystitis through 12 months follow-up | 
| Total length of hospital stay | it will be measured on both arms study when patients require hospitalization due to any procedure adverse event, cholecystitis and related procedures (cholecystectomy, percutaneous drainage) | from the beginning of hospitalization until discharge date or death since enrollment through 12 months follow-up | 
| Total health-care related cost of both arm participants. | total health-are related cost in all participants from each arm. | from the end of conventional biliary drainage until the date of 12 months follow-up. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endoscopic ultrasound, acute cholecystitis, cholangiocarcinoma, gallbladder drainage, metallic stents