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Trial registered on ANZCTR


Registration number
ACTRN12620000217909p
Ethics application status
Submitted, not yet approved
Date submitted
30/01/2020
Date registered
24/02/2020
Date last updated
24/02/2020
Date data sharing statement initially provided
24/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomized comparison of endoscopic bilateral stent-in-stent (SIS) versus stent-by-stent (SBS) placement for inoperable advanced malignant hilar biliary stricture: a multi-centre trial proposal.
Scientific title
Randomized comparison of endoscopic bilateral stent-in-stent (SIS) versus stent-by-stent (SBS) placement for inoperable advanced malignant hilar biliary stricture: a multi-centre trial proposal.
Secondary ID [1] 300387 0
none
Universal Trial Number (UTN)
Trial acronym
SIS vs SBS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Hilar Biliary Strictures 315997 0
Condition category
Condition code
Oral and Gastrointestinal 314283 314283 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 314290 314290 0 0
Biliary tree (gall bladder and bile duct)
Surgery 314539 314539 0 0
Surgical techniques

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
After obtaining informed consent, the recruited patients will be randomized, in a 1:1 ratio, to either the Stent-In-Stent (SIS) or Stent-By-Stent (SBS) group before insertion of a duodenoscope for the placement of bilateral metal stents, via Endoscopic Retrograde Cholangiopancreatography (ERCP). The randomization is computer generated random numbers for block randomization (block size of 16).

The ERCP procedure will be performed after an overnight fast. The patient’s position and mode of sedation will be at the discretion of the endoscopists. Prophylactic antibiotics should be used before, during, and 3 days after the ERCP procedure to minimize risk of cholangitis, which is substantially high in this group of patients. The requirement of a longer course of antibiotic will be guided at the judgement of the caring physician. Analgesics (Fentanyl or Meperidine) will be allowed during and after the procedure.

All cases will be performed by the participated investigators, who are highly experienced ERCP-ists at their own tertiary referral centres. Trainees will not be permitted to perform the endoscopic procedures. Careful pre-ERCP assessment of the biliary tract is essential and will be based on CT and/or MRCP images. Atrophied liver and dominant right or left portal vein occlusion sites with or without liver atrophy were avoided as much as possible to effectively drain the liver volume. Based on these findings, decision on which branch should be drained will be determined pre-ERCP. Overall, two of the 3 major hepatic branches, the right anterior, the right posterior, or the left lobe of the dominant biliary branch, will be selected for drainage. Temporary biliary decompression was permitted while waiting for pathologic confirmation and the decision regarding operability.

After defining the anatomy of the biliary tract and identifying the dominant branches that need to be drained, guidewires will be placed into the relevant ducts.

For SIS deployment: after insertion of the guidewires into both Intrahepatic Ducts (IHD), bilaterally, the first stent, with a radiopaque “X” mark, will be inserted into the left or right IHD. After deploying the first stent, a guidewire will be passed through the stent into the contralateral bile duct. Then, the second stent will be deployed through the wire mesh of the first stent.
For SBS deployment: after passing 2 guidewires into both IHDs using the same method as used for SIS deployment, the first stent will be deployed into the left hepatic duct and the second stent into the right hepatic duct sequentially. During deployment of the first stent, the second stent will be preloaded on a guidewire to facilitate immediate placement of the bilateral SBS.
For both groups, the expected duration of the ERCP procedure is 30-40 minutes.

In both SIS and SBS cases, the distal end of the stents will be positioned across the papilla (i.e. transpapillary placement). A generous endoscopic sphincterotomy will be routinely performed to accommodate the stents across the papilla and to reduce the risk of pancreatitis. Endoscopic dilatation of the stricture is allowed before deployment of a stent to facilitate the insertion of stent catheters across the strictures. The crossover method (SIS to SBS, or SBS to SIS) will be attempted when bilateral drainage failed using the intended method. If the crossover method failed, only the remaining unilateral stent will be left and the patient will be closely monitored for further intervention. Percutaneous transhepatic biliary drainage or Endoscopic Ultrasound-guided biliary drainage is allowed according to patient status as reintervention or rescue therapy. Chemotherapy or radiotherapy is allowed according to the patient’s condition and with their approval after randomization. Local therapies, such as photodynamic therapy or radiofrequency ablation, will not be performed.

Vital signs (heart rate, blood pressure, breathing rate, and oxygen level) will be monitored during the procedure. Clinical review bloods, and any nurse notes or clinical observations, following the procedure will be used to monitor fidelity.
Intervention code [1] 316675 0
Treatment: Surgery
Comparator / control treatment
Both techniques are already well-established for stent insertion, and considered as standard treatments at the Royal Adelaide Hospital.
However, there are no recommended guidelines regarding the choice between SIS and SBS deployment for hilar strictures, so for the purposes of this study the SIS group will be 'compared' with the SBS group.
Control group
Active

Outcomes
Primary outcome [1] 322691 0
Compare stent patency between the 2 placement techniques. Defined as the time between stent placement and potential stent exchange due to dysfunction. Assessed through clinical examination, CT or MRCP scan, and medical record review. Time between stent placement calculated by noting date and time of initial stent insertion and potential stent replacement.
Timepoint [1] 322691 0
Determined at 3 months and 6 months following stent placement.
Secondary outcome [1] 379305 0
Compare the technical success of SIS and SBS deployment techniques. Defined as successful deployment of bilateral stents across the hilar stricture site, along with a flow of contrast medium and/or bile through the stent, Observed via clinical examination immediately following stent insertion, and Endoscopic Retrograde Cholangiopancreatography.
Timepoint [1] 379305 0
Assessed within 48 hours of the stent procedure.
Secondary outcome [2] 379306 0
Compare the clinical success of SIS and SBS deployment techniques. Defined as a decrease in the total bilirubin level to <50% of the pre-treatment value within 1 week, or to <75% within 4 weeks, via biochemistry blood results.
Timepoint [2] 379306 0
Assessed at week 1 and/or week 4 following the stent procedure
Secondary outcome [3] 379307 0
Compare potential complications and malfunctions. Defined as a condition requiring any endoscopic or percutaneous intervention causing cholangitis or jaundice by tumour growth and/or overgrowth, sludge or stone formation, biloma, or liver abscess. Stent malfunction is revealed by abdominal CT or MRCP and ERCP in patients who had recurrent jaundice or cholangitis.
Timepoint [3] 379307 0
Evaluated at 3 months and 6 months following stent procedure, or by accessing patient records.

Eligibility
Key inclusion criteria
All patients who have pathologically confirmed inoperable Malignant Hilar Biliary Strictures (MHSs) of Bismuth type III or IV with an estimated survival >3 months (Eastern Cooperative Oncology Group scale, <2) will be eligible for recruitment into the study. All causes of malignancy are included.
The criteria for inoperability were based on imaging studies such as Computed Tomography (CT) scan, Magnetic resonance cholangiopancreatography imaging (MRCP); cholangiography; positron emission tomography-CT; presence of comorbidities; and consensus of the surgeons.
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Uncontrolled coagulopathy, American Society of Anaesthesiologist Class V, inaccessible papilla because of an accompanying duodenal obstruction or altered anatomy, and the inability to provide informed consent. Patients with MHSs caused by multiple metastatic lesions or lobes diffusely occupied by a massive tumour were also excluded because drainage could not be performed effectively and such cases have an inherently poor survival rate.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet 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)
SA
Recruitment hospital [1] 15706 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 29127 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 304801 0
Hospital
Name [1] 304801 0
Royal Adelaide Hospital
Address [1] 304801 0
Port Road, Adelaide, South Australia, 5000
Country [1] 304801 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Port Road, Adelaide, South Australia, 5000
Country
Australia
Secondary sponsor category [1] 305122 0
None
Name [1] 305122 0
Address [1] 305122 0
Country [1] 305122 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 305216 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 305216 0
Level 3, Roma Mitchell House, 136 North Terrace, Adelaide, South Australia, 5000
Ethics committee country [1] 305216 0
Australia
Date submitted for ethics approval [1] 305216 0
30/01/2020
Approval date [1] 305216 0
Ethics approval number [1] 305216 0

Summary
Brief summary
Who is it for?
You may be eligible for this study if you are 18 years or older, and have been diagnosed with a “Malignant Hilar Biliary Stricture” (or MHS), and require a stent.

Purpose of the Study
To assess two types of established stent placement techniques: Stent-By-Stent (SBS) and Stent-In-Stent (SIS). They will be compared in terms of stent patency, technical success, and complication rates, which will be assess at the end of the procedure day, and two follow-up visits.

Study Details
All participants will undergo an Endoscopic Retrograde Cholandio-Pancreatography (or ERCP). This is performed under sedation, and you are not likely to feel the entire processs. The ERCP procedure uses a thin tube with a camera which passes into your throat so we can have a better view of your gastrointestinal tract. The scope will travel down into the place where the bile duct meets the small intestine. A special dye will be injected into the affected bile ducts and an x-ray will be used to watch the flow of the dye to see where the blockage is. Then the stents will be put inside the relevant bile ducts using small guide-wires. Once the stent is inserted in the right place the wire is removed, and the bile duct will be unblocked and should drain normally.

Because of your condition, you will require two stents placed in the ‘left’ and ‘right’ hepatic ducts within the liver. If you agree to participate, you have an equal chance of being randomised to receive one of the two stent placement techniques; SBS or SIS.
(1) For the SBS group, two separate guide-wires will be fed into the left and right bile ducts at the same time. The first stent will be deployed into the left duct, and then the second stent will then be deployed into the right duct, and the guide-wires are removed.
(2) For the SIS group, the first guide-wire will be fed into the left or right duct, and the stent will then be deployed and the guide-wire will be removed. Then, the second guide-wire will pass through the mesh of the first stent, into the remaining duct, and the second stent will be deployed while sitting through the first stent (creating a “Y” shape).

You will be asked to attend a review visit with the investigator at 3 months and 6 months following your procedure. Your ongoing treatment and follow up will then be planned by your treating practitioner.

We are particularly interested in investigating the choice of placement with a type of metallic stent, which has shown superior patency to plastic stents in recent studies. However, it is not clear which type of placement is favoured for metal stents for MHSs.
We hope this research will help provide further information on the safety and usefulness of stent insertion techniques of MHSs and potentially other gastrointestinal disorders that require stents

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99642 0
A/Prof Nam Nguyen
Address 99642 0
Department of Gastroenterology and Hepatology,
Royal Adelaide Hospital,
Port Road,
Adelaide,
South Australia, 5000
Country 99642 0
Australia
Phone 99642 0
+61 9 7074 2189
Fax 99642 0
+61 8 7074 6192
Email 99642 0
quocnam.nguyen@sa.gov.au
Contact person for public queries
Name 99643 0
Mrs Romina Safaeian
Address 99643 0
Department of Gastroenterology and Hepatology,
Royal Adelaide Hospital,
Port Road,
Adelaide,
South Australia, 5000
Country 99643 0
Australia
Phone 99643 0
+61 8 7074 2189
Fax 99643 0
+61 8 7074 6192
Email 99643 0
romina.safaeian@sa.gov.au
Contact person for scientific queries
Name 99644 0
Mrs Romina Safaeian
Address 99644 0
Department of Gastroenterology and Hepatology,
Royal Adelaide Hospital,
Port Road,
Adelaide,
South Australia, 5000
Country 99644 0
Australia
Phone 99644 0
+61 8 7074 2189
Fax 99644 0
+61 8 7074 6192
Email 99644 0
romina.safaeian@sa.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
All data will be de-identified, and there is no plan to make IPD publicly available.
What supporting documents are/will be available?
No other documents available
Summary results
No Results