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

Acute Cholecystitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03729882
• Other study ID #: EUS-GBD
• Status: Completed
• Phase: N/A
• Start date: July 1, 2018
• Est. completion date: July 27, 2020

Study information

• Verified date: July 2020
• Source: Instituto Ecuatoriano de Enfermedades Digestivas
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: July 27, 2020
• Est. primary completion date: December 27, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Cholecystitis
• Cholecystitis
• Cholecystitis, Acute

Intervention

Procedure:
• EUS-guided gallbladder drainage
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.
• Non EUS-guided gallbladder drainage
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

Locations

Country	Name	City	State
Ecuador	Instituto Ecuatoriano de Enfermedades Digestivas	Guayaquil	Guayas

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Ecuatoriano de Enfermedades Digestivas

Country where clinical trial is conducted

Ecuador, 

References & Publications (9)

Choi JH, Kim HW, Lee JC, Paik KH, Seong NJ, Yoon CJ, Hwang JH, Kim J. Percutaneous transhepatic versus EUS-guided gallbladder drainage for malignant cystic duct obstruction. Gastrointest Endosc. 2017 Feb;85(2):357-364. doi: 10.1016/j.gie.2016.07.067. Epub 2016 Aug 24. — View Citation

Dollhopf M, Larghi A, Will U, Rimbas M, Anderloni A, Sanchez-Yague A, Teoh AYB, Kunda R. EUS-guided gallbladder drainage in patients with acute cholecystitis and high surgical risk using an electrocautery-enhanced lumen-apposing metal stent device. Gastrointest Endosc. 2017 Oct;86(4):636-643. doi: 10.1016/j.gie.2017.02.027. Epub 2017 Mar 1. — View Citation

Gosain S, Bonatti H, Smith L, Rehan ME, Brock A, Mahajan A, Phillips M, Ho HC, Ellen K, Shami VM, Kahaleh M. Gallbladder stent placement for prevention of cholecystitis in patients receiving covered metal stent for malignant obstructive jaundice: a feasibility study. Dig Dis Sci. 2010 Aug;55(8):2406-11. doi: 10.1007/s10620-009-1024-9. Epub 2009 Nov 4. — View Citation

Hatanaka T, Itoi T, Ijima M, Matsui A, Kurihara E, Okuno N, Kobatake T, Kakizaki S, Yamada M. Efficacy and Safety of Endoscopic Gallbladder Stenting for Acute Cholecystitis in Patients with Concomitant Unresectable Cancer. Intern Med. 2016;55(11):1411-7. doi: 10.2169/internalmedicine.55.5820. Epub 2016 Jun 1. — View Citation

Irani S, Ngamruengphong S, Teoh A, Will U, Nieto J, Abu Dayyeh BK, Gan SI, Larsen M, Yip HC, Topazian MD, Levy MJ, Thompson CC, Storm AC, Hajiyeva G, Ismail A, Chen YI, Bukhari M, Chavez YH, Kumbhari V, Khashab MA. Similar Efficacies of Endoscopic Ultrasound Gallbladder Drainage With a Lumen-Apposing Metal Stent Versus Percutaneous Transhepatic Gallbladder Drainage for Acute Cholecystitis. Clin Gastroenterol Hepatol. 2017 May;15(5):738-745. doi: 10.1016/j.cgh.2016.12.021. Epub 2016 Dec 30. — View Citation

Isayama H, Kawabe T, Nakai Y, Tsujino T, Sasahira N, Yamamoto N, Arizumi T, Togawa O, Matsubara S, Ito Y, Sasaki T, Hirano K, Toda N, Komatsu Y, Tada M, Yoshida H, Omata M. Cholecystitis after metallic stent placement in patients with malignant distal biliary obstruction. Clin Gastroenterol Hepatol. 2006 Sep;4(9):1148-53. Epub 2006 Aug 14. — View Citation

Nakai Y, Isayama H, Kawakubo K, Kogure H, Hamada T, Togawa O, Ito Y, Matsubara S, Arizumi T, Yagioka H, Takahara N, Uchino R, Mizuno S, Miyabayashi K, Yamamoto K, Sasaki T, Yamamoto N, Hirano K, Tada M, Koike K. Metallic stent with high axial force as a risk factor for cholecystitis in distal malignant biliary obstruction. J Gastroenterol Hepatol. 2014;29(7):1557-62. doi: 10.1111/jgh.12582. — View Citation

Shimizu S, Naitoh I, Nakazawa T, Hayashi K, Miyabe K, Kondo H, Yoshida M, Yamashita H, Umemura S, Hori Y, Ohara H, Joh T. Predictive factors for pancreatitis and cholecystitis in endoscopic covered metal stenting for distal malignant biliary obstruction. J Gastroenterol Hepatol. 2013 Jan;28(1):68-72. doi: 10.1111/j.1440-1746.2012.07283.x. — View Citation

Xu MM, Kahaleh M. EUS-guided transmural gallbladder drainage: a new era has begun. Therap Adv Gastroenterol. 2016 Mar;9(2):138-40. doi: 10.1177/1756283X15618178. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	adverse events	any procedure-related adverse event (anesthesia, EUS-GBD, ERCP).	from the beginning of the procedure until 30 days.
Secondary	presence of pus during EUS-GBD	endoscopic visualization of pus after EUS-GBD. Yes or no.	immediate after EUS-GBD.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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.