Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography for Malignant Distal Biliary Obstruction

Pancreatic Cancer Clinical Trial

Official title:

Randomized Trial Comparing Endoscopic Ultrasound-guided Biliary Drainage (EUS-BD) and Endoscopic Retrograde Cholangiopancreatography (ERCP) for Malignant Distal Biliary Obstruction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03054987
• Other study ID #: 758636
• Status: Completed
• Phase: N/A
• Start date: September 2016
• Est. completion date: October 2018

Study information

• Verified date: February 2019
• Source: Florida Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the rates of adverse events between patients undergoing Endoscopic Ultrasound- guided biliary drainage and Endoscopic Retrograde Cholangiopancreatography for distal malignant biliary obstruction.

Description:

The current curative treatment for patients with occlusion of the distal common bile duct by pancreatic cancer is pancreaticoduodenectomy (Whipple procedure). Unfortunately, more than 80% of patients have locally advanced or metastatic disease that requires neoadjuvant or palliative treatment. The goals of biliary drainage in the setting of locally advanced or metastatic pancreatic cancer are to palliate obstructive jaundice and lower serum bilirubin prior to systemic chemotherapy. In addition to resolving jaundice and associated pruritus, biliary drainage improves anorexia, indigestion and quality of life (1, 2). Endoscopic approach by means of retrograde cholangiopancreatography (ERCP) and biliary stent placement is the preferred treatment option for palliation of malignant obstructive jaundice. Endoscopic biliary drainage is safer than surgical bypass, with endoscopic placement of a plastic or metal stent having a lower relative risk of complications (3). When performed by experts, ERCP has favorable (80-90%) short-term (<90 days) success rates in the setting of malignant distal biliary obstruction (1-3). The rate of ERCP-associated adverse events (AEs) is 5-27% (4-7) and include pancreatitis, bleeding, infection, perforation and rarely death.

In a recent audit of 524 consecutive patients with an intact papilla who underwent ERCP at a tertiary endoscopy unit, 49 (9.4%) had a previously failed attempt at an outside facility and more than 80% of these failures were in the setting of a distal malignant stricture (8). Cancer in the pancreatic head or uncinate process can cause extensive ampullary inflammation that precludes successful biliary cannulation using standard techniques. In such circumstances, advanced techniques such as needle-knife sphincterotomy, dual wire technique, trans-papillary pancreatic sphincterotomy and cannulation over a pancreatic duct stent are performed to access the bile duct (9, 10). While the technical success rate for advanced techniques in expert hands is more than 85%, the procedure is associated with an AE rate of about 10-20% (9-11).

When ERCP is technically unsuccessful, patients are usually referred for interventional radiology-guided percutaneous transhepatic biliary drainage (PTBD). PTBD is usually a multi-step procedure that involves the initial placement of an external drainage catheter followed by internal trans-papillary stent placement. When the distal bile duct is severely strictured or when the intra-hepatic biliary system is non-dilated, PTBD is unsuccessful and is encountered in about 5-15% of patients with pancreatic cancer (12). The rate of short and long-term PTBD-related AEs is 5-10% and 20-30%, respectively (12-14). While most short-term AEs are due to infection and bleeding, the long-term AEs are due to stent dysfunction requiring frequent readmissions (12-14).

More recently, EUS-guided biliary drainage (EUS-BD) has emerged as a novel alternative to PTBD and ERCP for biliary decompression when advanced cannulation techniques fail. EUS-BD is a minimally invasive technique where the extra-hepatic common bile duct (choledochoduodenostomy) or intrahepatic bile duct (hepatogastrostomy) is punctured under EUS-guidance and after transmural dilation a stent is deployed for biliary drainage.

The potential advantages of EUS-BD are three-fold. Firstly, EUS-BD can be performed from multiple routes in the stomach and duodenum. Thus, duodenal stenosis is not a limitation to biliary access. Secondly, as biliary access is gained distant from the major duodenal papilla, the risk of post-procedure pancreatitis is low. Thirdly, as the deployed stent does not traverse the tumor, its patency could be longer. In a recent study of 95 patients with failed ERCP or inaccessible papilla, direct EUS-guided biliary drainage was successful in 86% of patients with an AE rate of 10.5% that included pancreatitis, bleeding, perforation, bile leak and infection (15). Most AEs were managed conservatively without the need for aggressive treatment measures. In another small, randomized trial of 25 patients with inoperable malignant biliary obstruction, there was no difference in clinical success, AEs, and costs between patients randomized to EUS-BD or PTBD (16). In a recent retrospective study of 208 patients with malignant obstructive jaundice treated by ERCP or EUS-BD directed biliary metal stent placement, there was no difference in the rates of technical success (>90% in both cohorts) or AEs (8.65% in both cohorts) between groups (17). However, patients who underwent ERCP had a 5% incidence of post-procedure pancreatitis compared to 0% in the EUS-BD cohort. Given these promising outcomes, EUS-BD is currently practiced as a complimentary therapy that allows biliary drainage when technical failure is encountered at ERCP. EUS-BD and PTBD have been shown to be comparable in effectiveness after failed ERCP, however patients who underwent PTBD had higher rates of adverse events and required additional interventions (19).

PTBD and EUS-BD have shown to be equally effective treatment options (16). The effectiveness of treatment outcomes between EUS-BD and ERCP needs to be evaluated. Since the treatment outcomes and safety profile of EUS-BD is comparable to ERCP and because EUS-BD is successful in more than 85% of patients with a failed ERCP, EUS-BD could be a first-line treatment option and not just a rescue measure for patients with malignant distal biliary obstruction.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: October 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

1. = 18 years of age.

2. Has jaundice due to malignant distal (more than 3cm distal to liver hilum) biliary obstruction.

3. The subject (or when applicable the subject's LAR) is able to understand and willing to sign an informed consent form prior to the initiation of any study procedures.

Exclusion Criteria:

1. Age <18 years

2. Females who are pregnant or lactating. Pregnancy in females of childbearing potential will be determined by routine preoperative urine HCG testing.

3. Coagulopathy which cannot be corrected (INR >1.6, thrombocytopenia with platelet count <50,000/ml)

4. Has surgically altered gastrointestinal anatomy such as but not limited to (Billroth II/Roux en-Y, gastric bypass).

5. Liver metastasis involving >30% of liver volume.

6. Liver cirrhosis with portal hypertension and/or ascites.

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Adenocarcinoma
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Procedure:
• EUS-BD
EUS-BD is a minimally invasive technique where the common bile duct (choledochoduodenostomy) is punctured under EUS-guidance and after transmural dilation, a stent is deployed for biliary drainage.
• ERCP
During the ERCP, a small catheter and guidewire is inserted into the bile duct and the stent can be deployed into the duct.

Locations

Country	Name	City	State
United States	Center for Interventional Endoscopy - Florida Hospital	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Florida Hospital

Country where clinical trial is conducted

United States, 

References & Publications (19)

Andriulli A, Loperfido S, Napolitano G, Niro G, Valvano MR, Spirito F, Pilotto A, Forlano R. Incidence rates of post-ERCP complications: a systematic survey of prospective studies. Am J Gastroenterol. 2007 Aug;102(8):1781-8. Epub 2007 May 17. Review. — View Citation

Artifon EL, Aparicio D, Paione JB, Lo SK, Bordini A, Rabello C, Otoch JP, Gupta K. Biliary drainage in patients with unresectable, malignant obstruction where ERCP fails: endoscopic ultrasonography-guided choledochoduodenostomy versus percutaneous drainage. J Clin Gastroenterol. 2012 Oct;46(9):768-74. doi: 10.1097/MCG.0b013e31825f264c. — View Citation

Barkay O, Mosler P, Schmitt CM, Lehman GA, Frakes JT, Johanson JF, Qaseem T, Howell DA, Sherman S. Effect of endoscopic stenting of malignant bile duct obstruction on quality of life. J Clin Gastroenterol. 2013 Jul;47(6):526-31. doi: 10.1097/MCG.0b013e318272440e. — View Citation

Coelho-Prabhu N, Shah ND, Van Houten H, Kamath PS, Baron TH. Endoscopic retrograde cholangiopancreatography: utilisation and outcomes in a 10-year population-based cohort. BMJ Open. 2013 May 31;3(5). pii: e002689. doi: 10.1136/bmjopen-2013-002689. — View Citation

Cotton PB, Eisen GM, Aabakken L, Baron TH, Hutter MM, Jacobson BC, Mergener K, Nemcek A Jr, Petersen BT, Petrini JL, Pike IM, Rabeneck L, Romagnuolo J, Vargo JJ. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc. 201 — View Citation

Crosara Teixeira M, Mak MP, Marques DF, Capareli F, Carnevale FC, Moreira AM, Ribeiro U Jr, Cecconello I, Hoff PM. Percutaneous transhepatic biliary drainage in patients with advanced solid malignancies: prognostic factors and clinical outcomes. J Gastrointest Cancer. 2013 Dec;44(4):398-403. doi: 10.1007/s12029-013-9509-3. — View Citation

Dhir V, Itoi T, Khashab MA, Park DH, Yuen Bun Teoh A, Attam R, Messallam A, Varadarajulu S, Maydeo A. Multicenter comparative evaluation of endoscopic placement of expandable metal stents for malignant distal common bile duct obstruction by ERCP or EUS-guided approach. Gastrointest Endosc. 2015 Apr;81(4):913-23. doi: 10.1016/j.gie.2014.09.054. Epub 2014 Dec 5. — View Citation

Glomsaker T, Hoff G, Kvaløy JT, Søreide K, Aabakken L, Søreide JA; Norwegian Gastronet ERCP Group. Patterns and predictive factors of complications after endoscopic retrograde cholangiopancreatography. Br J Surg. 2013 Feb;100(3):373-80. doi: 10.1002/bjs.8992. Epub 2012 Dec 6. — View Citation

Holt BA, Hawes R, Hasan M, Canipe A, Tharian B, Navaneethan U, Varadarajulu S. Biliary drainage: role of EUS guidance. Gastrointest Endosc. 2016 Jan;83(1):160-5. doi: 10.1016/j.gie.2015.06.019. Epub 2015 Jul 26. — View Citation

Kahaleh M, Tokar J, Mullick T, Bickston SJ, Yeaton P. Prospective evaluation of pancreatic sphincterotomy as a precut technique for biliary cannulation. Clin Gastroenterol Hepatol. 2004 Nov;2(11):971-7. — View Citation

Khashab MA, Valeshabad AK, Afghani E, Singh VK, Kumbhari V, Messallam A, Saxena P, El Zein M, Lennon AM, Canto MI, Kalloo AN. A comparative evaluation of EUS-guided biliary drainage and percutaneous drainage in patients with distal malignant biliary obstruction and failed ERCP. Dig Dis Sci. 2015 Feb;60(2):557-65. doi: 10.1007/s10620-014-3300-6. Epub 2014 Aug 1. — View Citation

Lee E, Gwon DI, Ko GY, Sung KB, Yoon HK, Shin JH, Kim JH, Ko HK, Song HY. Percutaneous biliary covered stent insertion in patients with malignant duodenobiliary obstruction. Acta Radiol. 2015 Feb;56(2):166-73. doi: 10.1177/0284185114523267. Epub 2014 Feb 11. — View Citation

Lee JH, Krishna SG, Singh A, Ladha HS, Slack RS, Ramireddy S, Raju GS, Davila M, Ross WA. Comparison of the utility of covered metal stents versus uncovered metal stents in the management of malignant biliary strictures in 749 patients. Gastrointest Endosc. 2013 Aug;78(2):312-24. doi: 10.1016/j.gie.2013.02.032. Epub 2013 Apr 13. — View Citation

Moss AC, Morris E, Mac Mathuna P. Palliative biliary stents for obstructing pancreatic carcinoma. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004200. Review. — View Citation

Pereira-Lima JC, Jakobs R, Maier M, Kohler B, Benz C, Martin WR, Riemann JF. Endoscopic stenting in obstructive jaundice due to liver metastases: does it have a benefit for the patient? Hepatogastroenterology. 1996 Jul-Aug;43(10):944-8. — View Citation

Shah JN, Marson F, Weilert F, Bhat YM, Nguyen-Tang T, Shaw RE, Binmoeller KF. Single-operator, single-session EUS-guided anterograde cholangiopancreatography in failed ERCP or inaccessible papilla. Gastrointest Endosc. 2012 Jan;75(1):56-64. doi: 10.1016/j.gie.2011.08.032. Epub 2011 Oct 21. — View Citation

Swan MP, Alexander S, Moss A, Williams SJ, Ruppin D, Hope R, Bourke MJ. Needle knife sphincterotomy does not increase the risk of pancreatitis in patients with difficult biliary cannulation. Clin Gastroenterol Hepatol. 2013 Apr;11(4):430-436.e1. doi: 10.1016/j.cgh.2012.12.017. Epub 2013 Jan 11. — View Citation

Williams EJ, Taylor S, Fairclough P, Hamlyn A, Logan RF, Martin D, Riley SA, Veitch P, Wilkinson ML, Williamson PR, Lombard M. Risk factors for complication following ERCP; results of a large-scale, prospective multicenter study. Endoscopy. 2007 Sep;39(9):793-801. — View Citation

Zhang GY, Li WT, Peng WJ, Li GD, He XH, Xu LC. Clinical outcomes and prediction of survival following percutaneous biliary drainage for malignant obstructive jaundice. Oncol Lett. 2014 Apr;7(4):1185-1190. Epub 2014 Feb 7. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rates of perforation	As defined by evidence of air or luminal contents outside the GI tract	1 week
Primary	Rates of pancreatitis	Defined as typical pain with amylase/lipase >3 times normal	1 week
Primary	Rates of bile leak	Not caused by pancreatitis or perforation	1 week
Primary	Rates of bleeding	As defined by "A lexicon for endoscopic adverse events: report of an ASGE workshop" PMID: 20189503	1 week
Primary	Rates of infection (cholangitis)	As defined by >38C >24 hours with cholestasis	1 week
Primary	Rates of peritionitis	As defined by "A lexicon for endoscopic adverse events: report of an ASGE workshop" PMID: 20189503	1 week
Primary	Rates of cholecystitis	As defined by "A lexicon for endoscopic adverse events: report of an ASGE workshop" PMID: 20189503	1 week
Primary	Rates of pneumoperitoneum	As defined by "A lexicon for endoscopic adverse events: report of an ASGE workshop" PMID: 20189503	1 week
Primary	Rates of fever	Defined as temperature >38C	1 week
Primary	Rates of abdominal pain	Defined as pain described by the patient not caused by pancreatitis or perforation	1 week
Primary	Rates of death attributable to the procedure.	As defined by "A lexicon for endoscopic adverse events: report of an ASGE workshop" PMID: 20189503	1 week
Secondary	Technical Success	Defined as successful placement of a stent for malignant distal biliary obstruction in the desired location as determined at ERCP and EUS in the index session.	1 day
Secondary	Treatment success	Clinical success is defined as decrease in direct bilirubin by 50% at 2 weeks	2 weeks
Secondary	Procedural duration	Defined as the time between procedure onset and completion of the procedure (stent deployment). The duration will be calculated in minutes from the time the echoendoscope or duodenoscope is positioned and the stent is deployed.	1 day
Secondary	Reintervention	Need for additional intervention (endoscopic, surgical or radiological) to relieve jaundice in the presence of dilated biliary system	6 months