Randomized Controlled Trial Comparing Covered Versus Uncovered Metal Stents for Biliary Decompression in Inoperable Malignant Distal Bile Duct Obstruction
Phase: NA
Conditions: Distal Bile Duct Obstruction
Sponsor: Vanderbilt University Medical Center

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Randomized controlled trial comparing covered metal stents versus uncovered 
metal stents for palliative biliary decompression in inoperable malignant distal 
bile duct obstruction 
 
 
 
Participating centers: 
Vanderbilt University Medical Center 
 
Principal Investigator: 
Patrick Yachimski, MD MPH 
 
 
Version Date: September 23, 2019 
 
 

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Background: 
Endoscopic retrograde cholangiopancreatography (ERCP) with transpapillary placement of an 
endoprosthesis is an established intervention for palliation of malignant distal extrahepatic bile duct 
obstruction.  Such intervention may provide relief of jaundice and pruritus, reduce the risk of ascending 
cholangitis, and permit administration of systemic chemotherapy.  Plastic biliary stents are prone to 
stent occlusion and malfunction, with median stent patency duration of 12 weeks for 8 French gauge 
stents and 32 weeks for 10 French gauge stents1, and therefore require repeat intervention via ERCP for 
stent removal and exchange every several months.  The need for repeat intervention may require 
interruption of ongoing chemotherapy, may be otherwise undesirable from a patient perspective, and 
may have cost implications.  Indeed, the goal of endoscopic biliary decompression should be to provide 
durable biliary drainage—ideally extending for the duration of the patient’s overall survival—in a single 
intervention. 
Self-expanding metal biliary stents (SEMS) offer an internal diameter up to 10 mm, offer more durable 
biliary drainage compared to plastic stents2,3, and have therefore become the endoprosthetic of choice 
for palliation of inoperable malignant distal bile duct obstruction.  Variations in SEMS design exist, 
however, and the choice of ideal SEMS is uncertain—uncovered SEMS (U-SEMS) consist of a bare metal 
scaffold which may be prone to hyperplastic tissue ingrowth and stent occlusion; alternatively, covered 
SEMS (C-SEMS) feature a polyurethane coating which may prevent tissue ingrowth but which may 
increase the likelihood of inadvertent stent migration.  A prior randomized controlled trial of a stainless 
steel U-SEMS versus a stainless steel partially covered C-SEMS revealed no difference in time to 
recurrent biliary obstruction4; and a recent meta-analysis demonstrated no clear advantage of C-SEMS 
vs U-SEMS5. 
Due to variations in stent material, design, and manufacture, however, such data may not be 
generalizable to current generation metal stents, which feature a nickel titanium alloy scaffold and 
which, in C-SEMS version, offer a full rather than partial polyurethane coating. 
Hypothesis: 
We hypothesize that current generation C-SEMS offer more durable biliary drainage and will decrease 
the need for biliary reintervention compared to U-SEMS in patients with inoperable malignant distal bile 
duct obstruction. 
Objectives: 
Primary objective: Compare the rate of long-term stent failure, defined as need for repeat biliary 
intervention (endoscopic, percutaneous, or surgical) following placement of C-SEMS vs U-SEMS for 
palliation of inoperable malignant distal bile duct obstruction. 
Secondary objective: Compare the rate of adverse stent-related or intervention-related outcomes 
(pancreatitis, cholangitis, cholecystitis, perforation) following placement of C-SEMS vs U-SEMS for 
palliation of inoperable malignant distal bile duct obstruction. 

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Design: 
Single-center prospective randomized controlled trial.   
Inclusion criteria: 
• 
Patients with distal bile duct obstruction due to pancreatic cancer, cholangiocarcinoma, or 
metastatic malignancy with a confirmed tissue diagnosis referred for ERCP with intended 
palliative metal stent placement for palliation of jaundice 
• 
Patients 18 years of age and older 
• 
Serum bilirubin > 2 mg/dL 
Exclusion criteria: 
• 
Prior endoscopic or percutaneous biliary drainage 
• 
Post-surgical anatomy (ie pancreaticoduodenectomy, Billroth-type gastrectomy, Roux-en Y 
hepaticojejunostomy) 
• 
Primary site of biliary obstruction involving the common hepatic duct or hilum 
• 
Tumor involving gastric outlet, duodenum, or ampulla either precluding endoscopic access to 
the papilla or otherwise preventing endoscopic biliary cannulation 
• 
Inability to provide written informed consent 
Procedure: 
• 
Patients will undergo ERCP under either MAC/general anesthesia or conscious sedation per 
institutional standard of care. 
• 
Following endoscopic biliary cannulation and diagnostic cholangiography, performed per 
standard of care, a sealed envelope will be opened to determine patient randomization to either 
a 10 mm diameter C-SEMS (Wallflex, Boston Scientific) or a 10 mm diameter U-SEMS (Wallflex, 
Boston Scientific).  Due to the nature of the intervention, the proceduralist will not be blinded to 
study allocation.  The choice of a 40 mm or 60 mm stent length will be at the discretion of the 
proceduralist. 
• 
Post-procedure monitoring and discharge will be performed per institutional standard of care. 
Follow-up: 
• 
Day 1 follow-up for assessment of post-procedural adverse events will be performed by 
telephone call by an endoscopy post-assessment nurse (for outpatients) or by physician 
assessment at the patient’s bedside (for inpatients), as per current institutional standard of care 
• 
Follow-up will occur every 60 days by review of the electronic medical record or patient self-
report to assess for primary and secondary study outcomes 
 
 

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Major treatment outcomes: 
• 
Primary outcome: Performance of repeat ERCP, percutaneous biliary drainage, or surgical biliary 
bypass for palliation of persistent or recurrent biliary obstruction. 
• 
Secondary outcomes: pancreatitis requiring hospital admission; cholangitis requiring hospital 
admission and intravenous antibiotics; cholecystitis requiring percutaneous, surgical, or 
endoscopic intervention; perforation. 
Sample size and planned statistical analysis: 
Retrospective data from VUMC has identified a long-term 25% failure rate of U-SEMS and 0% failure rate 
of C-SEMS when placed for palliation of malignant distal bile duct obstruction6.  Assuming a somewhat 
more conservative estimate of durability rates, a sample size of 96 patients (48 per treatment arm) 
would be required to detect a 20% difference in stent failure rates at 80% power with an alpha level of 
0.05.  Also anticipating a 20% rate of dropout/loss to follow-up, the goal would be to enroll and 
randomize 116 total patients in the study. 
Fisher’s exact test will be used to assess the statistical significance in proportion of primary and 
secondary study outcomes, respectively.  Additional univariate and multiple variable logistic regression 
analysis will be used to identify potential predictors of stent failure, to be reported including odds ratio 
and 95% confidence intervals.  A two-sided P value of <0.05 will be the threshold for statistical 
significance in all cases. 
Role of industry: 
This is an investigator-initiated study.  The stent manufacturer (Boston Scientific) has no role in the 
design, conduct, data collection or data analysis, reporting, monitoring, or funding of this study. 

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References: 
1) Speer AG, Cotton PB, MacRae KD. Endoscopic management of malignant biliary obstruction: 
stents of 10 French gauge are preferable to stents of 8 French gauge. Gastrointest Endosc 1988; 
34: 412-7. 
2) Davids PH, Groen AK, Rauws EA et al. Randomised trial of self-expanding metal stents versus 
polyethylene stents for distal malignant biliary obstruction. Lancet 1992; 340: 1488-92. 
3) Kaassis M, Boyer J, Dumas R et al. Plastic or metal stents for malignant stricture of the common 
bile duct? Results of a randomized prospective study. Gastrointest Endosc 2003; 57: 178-82. 
4) Telford JJ, Carr-Locke DL, Baron TH et al. A randomized trial comparing uncovered and partially 
covered self-expandable metal stents in the palliation of distal malignant biliary obstruction. 
Gastrointest Endosc 2010; 72: 907-14. 
5) Almadi MA, Barkun AN, Martel M. No benefit of covered vs uncovered self-expandable metal 
stents in patients with malignant distal biliary obstruction: a meta-analysis. Clin Gastroenterol 
Hepatol 2013; 11: 27-37. 
6) Trawick E, Slaughter J, Yachimski P. Endoscopic biliary stent placement for palliation of jaundice 
due to pancreatic cancer: self-expanding metal stents offer more durable biliary drainage 
compared to plastic stents, and minimize need for biliary reintervention. Am J Gastroenterol 
2012; 107: S111. 
 
 

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Appendix A—Data Instrument 
 
Study ID: ___________ 
 
Demographics: 
 
Age______ 
 
Gender:  
M 
F 
 
Underlying diagnosis: 
 
Pancreatic CA  
Cholangio CA 
 
Other (specify)___________ 
Additional clinic data: 
Serum bilirubin (mg/dL) __________ 
Serum WBC______________ 
Prior cholecystectomy   
Y 
N 
Cholangiographic and technical procedure data: 
Stricture length at ERCP: __________cm 
Stricture extending to ampulla:  
Y 
N 
 
Endoscopic ampullary mass present: 
Y 
N 
Stricture involving cystic duct takeoff 
Y 
N 
indeterminate 
Randomization:  
C-SEMS  
U-SEMS 
Follow-up: 
Day 1 adverse events: pancreatitis 
cholangitis 
cholecystitis 
perforation 
none 
Day 30 (and at each 30 day interval thereafter): 
Patient alive:  Y 
N 
If deceased, days from stent placement until death: ___ 
Repeat ERCP since stent placement: 
Y 
N 
Percutaneous biliary drainage since stent placement: 
Y 
N 
Surgical biliary bypass since stent placement: 
Y 
N 
Surgical, endoscopic, or percutaneous gallbladder interventi