Plastic vs. Fully Covered Self Expanding Stents (FCSEMS) for Treatment of Anastomotic Bile Leaks Following Orthotopic Liver Transplant (OLT): a Randomized Controlled Trial
Phase: NA
Conditions: Bile Leak
Sponsor: Vanderbilt University Medical Center

Study title: Plastic stents vs fully covered self expanding metal stents (FCSEMS) for treatment of 
anastomotic bile leaks following orthotopic liver transplant: a randomized controlled trial  
 
Principal Investigator: Patrick Yachimski, MD MPH  
Revision Date:  October 11, 2017 
 
Background: 
Orthotopic liver transplant (OLT) can be a life-saving intervention for patients with decompensated liver 
disease.  Typical surgical biliary reconstruction at the time of OLT is creation of an anastomosis between 
the donor common hepatic duct and recipient bile duct.  Bile leaks arising from this anastomosis early in 
the post-transplant period are a known potential adverse event of OLT and may result in significant 
morbidity including intra-abdominal infection, need for repeat liver transplant, and death. 
Standard endoscopic management for anastomotic bile leaks following OLT has been endoscopic 
retrograde cholangiopancreatography (ERCP) with placement of a temporary plastic biliary 
endoprosthesis (stent) across the site of anastomotic leak.  While this intervention carries a high rate of 
technical success, clinical success is not universal.  In a retrospective study of patients undergoing ERCP 
for post-OLT anastomotic bile leak at VUMC between 2009 and 2014, ERCP with placement of a plastic 
stent resulted in resolution of bile leak in 60% of patients.  The remaining 40% of patients experienced 
refractory anastomotic bile leaks.  Patients with refractory anastomotic leaks were found to be at 
increased risk of surgical re-intervention, repeat transplant, and death [1]. 
An alternative to placement of a plastic biliary stent is placement of a fully covered self-expanding metal 
stent (FCSEMS).  FCSEMS have been granted United States Food & Drug Administration approval for 
categories of both malignant and benign bile duct disease.  Whereas a plastic stent functions largely as a 
wick to siphon bile flow, the theoretical advantage of a FCSEMS is that the relatively larger expansile 
diameter and membrane coating provide an actual and effective seal at the site of leak.  FCSEMS have 
been used successfully for salvage therapy of anastomotic bile leaks in the post-OLT population at VUMC 
[1], with no serious stent related adverse events and no cases of unsuccessful FCSEMS removal in this 
population.   
The objective of this study is to prospectively randomize patients found to have anastomotic bile leaks 
following OLT to placement of either a plastic biliary stent or a FCSEMS at initial ERCP intervention. 
Study hypothesis: 
Placement of FCSEMS as initial treatment for anastomotic bile leak following OLT will result in a higher 
rate of leak resolution compared to placement of a plastic stent. 
Study endpoints/outcome measures: 
Primary endpoint:  
Cholangiographic resolution of bile leak at follow-up ERCP 6 weeks following placement of a plastic stent 
or FCSEMS. 
Secondary endpoints:  

Study title: Plastic stents vs fully covered self expanding metal stents (FCSEMS) for treatment of 
anastomotic bile leaks following orthotopic liver transplant: a randomized controlled trial  
 
Principal Investigator: Patrick Yachimski, MD MPH  
Revision Date:  October 11, 2017 
 
1) Need for repeat endoscopic intervention (ERCP) within initial 8 weeks following placement 
of a plastic stent or FCSEMS 
2) Need for percutaneous drainage of biloma or intraabdominal fluid collection following 
placement of a plastic stent or FCSEMS 
3) Need for surgical biliary reconstruction for refractory anastomotic  bile leak 
4) Need for repeat OLT 
5) Death at 90 days 
6) Rate of post-ERCP pancreatitis (PEP) following placement of a plastic stent vs FCSEMS 
7) Rate of stent migration following placement of a plastic stent vs FCSEMS 
8) Rate of anastomotic biliary stricture at follow-up ERCP 8 weeks following placement of a 
plastic stent or FCSEMS 
9) Need for repeat ERCP for management of anastomotic  biliary stricture within 90 days 
following leak resolution 
Methods: 
Eligibility: All adult patients undergoing ERCP for suspected anastomotic bile leak within 60 days 
following OLT with standard biliary reconstruction will be eligible for study participation.  Clinical 
decision to proceed with ERCP will be at the discretion of the liver transplant service when a bile leak is 
suspected on the basis of bilious percutaneous drain output, imaging findings, or other clinical criteria. 
Cognitively impaired population is eligible if surrogate has legal power of attorney. 
Patients who have undergone OLT with hepaticojejunostomy will not be eligible for participation.  
Patients who have undergone percutaneous transhepatic cholangiogram with percutaneous biliary 
intervention following OLT and prior to ERCP will not be eligible for participation. 
Study intervention: Potential subjects will be consented prior to ERCP.  ERCP will be performed in 
standard fashion.  If cholangiogram demonstrates a high-grade anastomotic bile leak (evident without 
occlusion cholangiogram) and successful transpapillary wire access across the leak is established, subject 
randomization will then take place.  Study allocation to plastic stent vs FCSEMS will be determined by 
the contents of a sealed envelope.  Patients randomized to plastic stents will receive a 10 French stent, 
with stent length sufficient to traverse both the anastomosis and papilla selected at the discretion of the 
endoscopist.  Patients randomized to FCSEMS will receive an 8 mm diameter by 80 mm length Wallflex 
(Boston Scientific) FCSEMS.  Consistent with current endoscopic practice among this population,  biliary 
sphincterotomy will be performed prior to stent placement unless prohibited by coagulopathy and/or 
thrombocytopenia. 
The study consists of a one-time intervention, randomization to plastic vs metal stent, during procedure 
while patient is under anesthesia.  There is no further study intervention, and all subsequent clinical 
interactions and procedures (if necessary) will be performed as part of standard (non-study) clinical 
care.  It is not expected that subjects will lose capacity or ability to withdraw consent.  However, if a 

Study title: Plastic stents vs fully covered self expanding metal stents (FCSEMS) for treatment of 
anastomotic bile leaks following orthotopic liver transplant: a randomized controlled trial  
 
Principal Investigator: Patrick Yachimski, MD MPH  
Revision Date:  October 11, 2017 
 
subject is identified as incapable of consenting on his/her own behalf, the individual authorized to 
provide consent for ERCP procedure will be identified as the individual authorized to provide consent for 
study participation.  That person must provide a legal power of attorney document. 
Study follow-up: All patients will be assessed by the gastroenterology consult service on post-operative 
day 1 following ERCP for the presence of post-procedure adverse events, as is typical practice. 
Patients will be scheduled for follow-up ERCP for stent removal at 6 weeks following initial placement of 
a plastic stent or FCSEMS.  Repeat ERCP may be performed sooner than 6 weeks at the discretion of the 
transplant team if there is clinical suspicion for refractory bile leak following initial stent placement. 
Adjudication of the primary study endpoint will be determined by the presence/absence of persistent 
anastomotic bile leak at first follow-up ERCP after initial stent placement, whether performed at 6 weeks 
or sooner. 
Study participation for all subjects will be complete at this point in time, with continued standard care as 
directed by the transplant time.  Additional secondary outcomes will be assessed by longitudinal follow-
up during a 90-day period following initial stent placement.   
Power calculation and statistical analysis plan:  Statistical comparison of the primary study outcome, 
proportion of patients with refractory bile leak, will be performed using Chi-square statistic.  Prior data 
indicate that the refractory anastomotic bile leak rate following placement of a plastic biliary stent is 
40% [1].  Assuming that the refractory leak rate following placement of a FCSEMS is 10%, this study 
would need to enroll 32 subjects in the plastic stent arm and 32 subjects in the FCSEMS arm to be able 
to reject the null hypothesis that the refractory leak rate for plastic vs FCSEMS is the same with 80% 
power and a Type I error rate of 0.05. 
Study timeline: Assuming an annual OLT volume of 150 patients at VUMC, and assuming 10% of OLT 
recipients will experience an anastomotic bile leak, we expect to enroll to study target (64) patients 
within a 4 to 5 year time frame. 
Study funding: The study will not be supported or funded by industry, and the collection, analysis, 
interpretation, and publication of data will be independent of industry. 
 
Reference: 
1) Davee T, Geevarghese SK, Slaughter JC, Yachimski PS.  Refractory anastomotic bile leak leaks 
after orthotopic liver transplantation are associated with hepatic artery disease.  Gastrointest 
Endosc 2016 Sep 10. pii: S0016-5107(16)30556-9. doi: 10.1016/j.gie.2016.08.050. [Epub ahead 
of print] 
 

Study title: Plastic stents vs fully covered self expanding metal stents (FCSEMS) for treatment of 
anastomotic bile leaks following orthotopic liver transplant: a randomized controlled trial  
 
Principal Investigator: Patrick Yachimski, MD MPH  
Revision Date:  October 11, 2017