Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography for Malignant Distal Biliary Obstruction

February 12, 2019 updated by: AdventHealth

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

67

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Orlando, Florida, United States, 32803
        • Center for Interventional Endoscopy - Florida Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: 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.
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.
Other Names:
  • Endoscopic Ultrasound-guided biliary drainage
ACTIVE_COMPARATOR: ERCP
At ERCP, the common bile duct will be selectively cannulated using a sphincterotome and guide wire technique. Once biliary access is obtained a stent will be deployed to facilitate biliary drainage.
Procedure: ERCP
During the ERCP, a small catheter and guidewire is inserted into the bile duct and the stent can be deployed into the duct.
Other Names:
  • Endoscopic Retrograde Cholangiopancreatography

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rates of perforation
Time Frame: 1 week
As defined by evidence of air or luminal contents outside the GI tract
1 week
Rates of pancreatitis
Time Frame: 1 week
Defined as typical pain with amylase/lipase >3 times normal
1 week
Rates of bile leak
Time Frame: 1 week
Not caused by pancreatitis or perforation
1 week
Rates of bleeding
Time Frame: 1 week
As defined by "A lexicon for endoscopic adverse events: report of an ASGE workshop" PMID: 20189503
1 week
Rates of infection (cholangitis)
Time Frame: 1 week
As defined by >38C >24 hours with cholestasis
1 week
Rates of peritionitis
Time Frame: 1 week
As defined by "A lexicon for endoscopic adverse events: report of an ASGE workshop" PMID: 20189503
1 week
Rates of cholecystitis
Time Frame: 1 week
As defined by "A lexicon for endoscopic adverse events: report of an ASGE workshop" PMID: 20189503
1 week
Rates of pneumoperitoneum
Time Frame: 1 week
As defined by "A lexicon for endoscopic adverse events: report of an ASGE workshop" PMID: 20189503
1 week
Rates of fever
Time Frame: 1 week
Defined as temperature >38C
1 week
Rates of abdominal pain
Time Frame: 1 week
Defined as pain described by the patient not caused by pancreatitis or perforation
1 week
Rates of death attributable to the procedure.
Time Frame: 1 week
As defined by "A lexicon for endoscopic adverse events: report of an ASGE workshop" PMID: 20189503
1 week

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Technical Success
Time Frame: 1 day
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
Treatment success
Time Frame: 2 weeks
Clinical success is defined as decrease in direct bilirubin by 50% at 2 weeks
2 weeks
Procedural duration
Time Frame: 1 day
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
Reintervention
Time Frame: 6 months
Need for additional intervention (endoscopic, surgical or radiological) to relieve jaundice in the presence of dilated biliary system
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AdventHealth

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 1, 2016

Primary Completion (ACTUAL)

September 1, 2018

Study Completion (ACTUAL)

October 1, 2018

Study Registration Dates

First Submitted

January 17, 2017

First Submitted That Met QC Criteria

February 13, 2017

First Posted (ACTUAL)

February 16, 2017

Study Record Updates

Last Update Posted (ACTUAL)

February 15, 2019

Last Update Submitted That Met QC Criteria

February 12, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 758636

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The data will be shared via publication and/or presentation.

IPD Sharing Supporting Information Type

  • SAP

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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