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Trial registered on ANZCTR


Registration number
ACTRN12619000776101
Ethics application status
Approved
Date submitted
26/04/2019
Date registered
24/05/2019
Date last updated
24/05/2019
Date data sharing statement initially provided
24/05/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
The utility of bile duct stent placement in liver transplantation
Scientific title
A randomized controlled non-inferiority trial comparing early outcomes following duct to duct biliary anastomosis either with or without stent placement in adult patients undergoing whole liver transplantation.
Secondary ID [1] 298062 0
None
Universal Trial Number (UTN)
TBA
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Biliary complications 312558 0
liver transplant 312896 0
Condition category
Condition code
Surgery 311077 311077 0 0
Surgical techniques
Oral and Gastrointestinal 311384 311384 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients in the treatment arm will not receive a biliary stent (no-stent group). Patients in the control arm will receive a stent (stent group).
No intervention is required in the treatment arm (no-stent group) as the biliary anastomosis is performed without a stent.
Inclusion and Exclusion criteria
Participants in the trial will be adult patients on the liver transplant waiting list who are planned to receive a whole liver allograft with a duct to duct biliary anastomosis from brain dead donors. Surgeons in the liver transplant team who have agreed to participate in this trial will have the allocation arm disclosed to them after complete graft reperfusion including completion of the arterial anastomosis. The allocation to stent or no-stent must be adhered to, to reduce selection bias. Contingency planning for a surgeon who is not comfortable with the allocation will be to have an alternative surgeon available to perform the anastomosis.
Patients will be excluded from the project if they are planned to receive any graft other than a whole liver from a brain dead donor. Given the higher biliary complication rate in split liver and DCD grafts these have been excluded. Patients who have a biliary reconstruction involving a hepaticoenterostomy will also be excluded. On occasion it is necessary to defer biliary reconstruction because of bleeding or because of recipient haemodynamic instability. This event occurs uncommonly, but has the potential to skew results because biliary complications are likely to be higher, and allocation may be asymmetrical across arms.

Approximate duration of surgery ranges from 4-12 hours.

Randomisation technique
Randomisation will be achieved by a computer-generated table using the online website (https://www.sealedenvelope.com). Allocation to study arms will be in a 1:1 ratio, in blocks of 20 to minimise asymmetrical allocation on completion of patient accrual. Each allocation (stent, or no stent) will be printed and placed in order (1-100) in an opaque sealed (with glue and staple) envelope by three investigators and stored within a secure combination-lock safe. Only the three investigators and the clinical nurse coordinator (CNC) for liver transplant in operating theatres will know the four-digit code to minimise any potential observer/investigator interference. One of these four persons will be available at the allocation time to access the the safe.
The description of the biliary anastomosis including whether or not a stent was placed will be documented in the operation report.
Intervention code [1] 314297 0
Treatment: Other
Comparator / control treatment
The intervention required in the control arm or stent group is the placement of a trans-anastomotic stent during the duct to duct anastomosis of a liver transplant. The stent is an infant feeding catheter composed of polyvinyl chloride cut to a length that allows it to be positioned across the anastomosis and through the Sphincter of Oddi. The length is approximately 150mm with the proximal end positioned in the common hepatic duct and the distal end in the duodenum. The diameter of the catheter used is at the surgeon discretion and is either 05 or 06 CH, corresponding to outer diameters of 1.67mm and 2.00mm respectively.
Patients with a stent will have an abdominal Xray performed 4 weeks postoperatively to assess if the stent is still present or if it has passed spontaneously through the alimentary system. If the stent remains in situ then an endoscopy will be arranged for stent removal.
Patient outcomes will be followed for a period of 6 months post transplant
No additional time is required to place the stent
Control group
Active

Outcomes
Primary outcome [1] 319864 0
Primary outcomes will be biliary complications including bile leak and stricture formation for a period of 6 months post transplant. These will be assessed as composite outcomes.
Bile leak is defined as a clinically significant leak resulting in delayed removal of postoperative drains or requiring intervention (percutaneous, endoscopic or operative).
Bile duct stricture is defined as a clinically significant stenosis requiring radiological or surgical intervention.
Outcomes will be assessed from hospital medical records including data linkage to radiology and gastroenterology reports
Timepoint [1] 319864 0
6 months post transplant
Secondary outcome [1] 369741 0
Secondary outcomes include requirement for further intervention including re-operation.
Outcomes will be assessed from hospital medical records including data linkage to radiology and gastroenterology reports
Timepoint [1] 369741 0
6 months post transplant
Secondary outcome [2] 370573 0
Secondary outcomes include requirement for further intervention including ERCP (endoscopic retrograde cholangiopancreatography)
Outcomes will be assessed from hospital medical records including data linkage to radiology and gastroenterology reports
Timepoint [2] 370573 0
6 months post transplant
Secondary outcome [3] 370574 0
Secondary outcomes include requirement for further intervention including percutaneous transhepatic cholangiography (PTC)
Outcomes will be assessed from hospital medical records including data linkage to radiology and gastroenterology reports
Timepoint [3] 370574 0
6 months post transplant
Secondary outcome [4] 370575 0
Mortality
Outcomes will be assessed from hospital medical records including data linkage to radiology, pathology and gastroenterology reports
Timepoint [4] 370575 0
6 months post transplant

Eligibility
Key inclusion criteria
Participants in the trial will be adult patients on the liver transplant waiting list who are planned to receive a whole liver allograft with a duct to duct biliary anastomosis from brain dead donors.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded from the project if they are planned to receive any graft other than a whole liver from a brain dead donor. Given the higher biliary complication rate in split liver and DCD grafts these have been excluded. Patients who have a biliary reconstruction involving a hepaticoenterostomy will also be excluded. On occasion it is necessary to defer biliary reconstruction because of bleeding or because of recipient haemodynamic instability. This event occurs uncommonly, but has the potential to skew results because biliary complications are likely to be higher, and allocation may be asymmetrical across arms.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation will occur prior to commencement of the study and will be blinded to all participants except the three investigators. Allocation will be revealed to the operating surgeon after the vascular anastomoses are completed during liver transplant. One of the three investigators or the CNC will access the safe and extract the opaque sealed envelope this will be opened and the allocation results read aloud to the surgeon. The patients will be blinded to the allocation until they are informed that an abdominal x-ray is required to assess stent position 4 weeks post liver transplant. Assessors will be independent of the randomization and allocation process.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be achieved by a computer-generated table using the online website (https://www.sealedenvelope.com). Allocation to study arms will be in a 1:1 ratio, in blocks of 20 to minimise asymmetrical allocation on completion of patient accrual. Each allocation (stent, or no stent) will be printed and placed in order (1-100) in an opaque sealed (with glue and staple) envelope by three investigators and stored within a secure combination-lock safe. Only the three investigators and the clinical nurse coordinator (CNC) for liver transplant in operating theatres will know the four-digit code to minimise any potential observer/investigator interference. One of these four persons will be available at the allocation time to access the safe.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
A sample size of 80 patients was calculated to provide a statistically significant result with 95% confidence and 80% power using an online power calculator (http://powerandsamplesize.com). The retrospective observational data generated from Ong et al showed a biliary complication rate of 29.9% and 7.9% in the control (stent group n=88) and treatment arms (no stent group n= 37) respectively. A 10% non-inferiority margin was deemed clinically acceptable.
Statistical analyses will be performed using SPSS software

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 13657 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 26340 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 302595 0
Hospital
Name [1] 302595 0
Princess Alexandra Hospital
Address [1] 302595 0
Dr Peter Hodgkinson
Acting Director Queensland Liver Transplant Service
Princess Alexandra Hospital
199 Ipswich Road
Woollongabba
QLD 4102
Country [1] 302595 0
Australia
Primary sponsor type
Hospital
Name
Princess Alexandra Hospital
Address
Dr Peter Hodgkinson
Acting Director Queensland Liver Transplant Service
Princess Alexandra Hospital
199 Ipswich Road
Woollongabba
QLD 4102
Country
Australia
Secondary sponsor category [1] 302504 0
None
Name [1] 302504 0
Address [1] 302504 0
Country [1] 302504 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303231 0
Metro South Health Human Research Ethics Committee
Ethics committee address [1] 303231 0
Centres for Health Research | Metro South Health
Level 7, Translational Research Institute, 37 Kent Street, WOOLLOONGABBA QLD 4102
Ethics committee country [1] 303231 0
Australia
Date submitted for ethics approval [1] 303231 0
04/09/2018
Approval date [1] 303231 0
13/11/2018
Ethics approval number [1] 303231 0
HREC/2018/QMS/43468

Summary
Brief summary
The purpose of this study is to quantitatively compare early outcomes following duct to duct anastomosis during whole liver transplantation with or without a biliary stent. Randomised comparative data showing non-inferiority in the stent-free group could result in fewer post-operative biliary/endoscopic interventions, and change our current, non-standardised practice.
Biliary stent placement during duct to duct anastomosis in whole liver transplantation confers no benefit with respect to biliary anastomotic complications when compared to a stent-free anastomosis but does result in a greater number of post-operative interventions to remove retained stents.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92934 0
Dr Sarah Byrne
Address 92934 0
Princess Alexandra Hospital
199 Ipswich Rd
Woolloongabba
QLD 4102
Country 92934 0
Australia
Phone 92934 0
+61 409244942
Fax 92934 0
Email 92934 0
sarah.byrne@health.qld.gov.au
Contact person for public queries
Name 92935 0
Dr Sarah Byrne
Address 92935 0
Princess Alexandra Hospital
199 Ipswich Rd
Woolloongabba
QLD 4102
Country 92935 0
Australia
Phone 92935 0
+61 409244942
Fax 92935 0
Email 92935 0
sarah.byrne@health.qld.gov.au
Contact person for scientific queries
Name 92936 0
Dr Sarah Byrne
Address 92936 0
Princess Alexandra Hospital
199 Ipswich Rd
Woolloongabba
QLD 4102
Country 92936 0
Australia
Phone 92936 0
+61 409244942
Fax 92936 0
Email 92936 0
sarah.byrne@health.qld.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 1948 0
Study protocol
Citation [1] 1948 0
Link [1] 1948 0
Email [1] 1948 0
Other [1] 1948 0
Summary results
No Results