Trial Title:
Treatment of Distal Malignant Biliary Obstruction by Uncovered, Partially Covered, or Fully Covered Metal Stents
NCT ID:
NCT06453590
Condition:
Pancreatic Cancer Non-resectable
Bile Duct Cancer
Papillary Carcinoma
Duodenal Cancer
Conditions: Official terms:
Bile Duct Neoplasms
Cholangiocarcinoma
Carcinoma, Papillary
Duodenal Neoplasms
Conditions: Keywords:
distal malignant biliary obstruction
ERCP
SEMS
Palliative
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Randomized controlled trial, to either of three groups.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Randomization to uncovered SEMS treating jaundice due to distal malignant biliary obstruction.
Description:
Patients with jaundice due to distal malignant biliary obstruction in whom surgical
resection is not possible are treated at ERCP with metal stents, SEMS. The study is
comparing three types of commercially available SEMS, Patients are randomized and
allocated to either of three stent types (SEMS), uncovered, partially covered , or fully
covered.
Arm group label:
Uncovered SEMS
Intervention type:
Procedure
Intervention name:
Randomization to partially covered SEMS treating jaundice due to distal malignant biliary obstruction.
Description:
Patients with jaundice due to distal malignant biliary obstruction in whom surgical
resection is not possible are treated at ERCP with metal stents, SEMS. The study is
comparing three types of commercially available SEMS, Patients are randomized and
allocated to either of three stent types (SEMS), uncovered, partially covered , or fully
covered.
Arm group label:
Partially covered SEMS
Intervention type:
Procedure
Intervention name:
Randomization to fully covered SEMS treating jaundice due to distal malignant biliary obstruction.
Description:
Patients with jaundice due to distal malignant biliary obstruction in whom surgical
resection is not possible are treated at ERCP with metal stents, SEMS. The study is
comparing three types of commercially available SEMS, Patients are randomized and
allocated to either of three stent types (SEMS), uncovered, partially covered , or fully
covered.
Arm group label:
Fully covered SEMS
Summary:
The goal of this randomized controlled trial is to compare uncovered, partially covered,
and fully covered self-expandable metal stents (SEMS) in the palliative treatment of
distal malignant biliary obstruction in a Swedish multicenter study.
The main questions it aims to answer is: Is the stent patency rate different depending of
stent type? Is the stent patency time different depending of stent type? Is the patient
survival different between the groups? Which complications are seen, and do they differ
between the groups? Are there different mechanisms behind the stent failure depending on
stent type?
Patients will at ERCP, with a guidewire passed through the stenosis in the bile duct, be
allocated to either uncovered, partially covered, and fully covered (SEMS). Totally, 450
patients will be recruited, 150 in each study arm, according to the power analysis.
Patients will be followed in a monthly surveillance by a study nurse up to 12 months
after stent insertion. Endpoints are: alive after 12 months with a patent stent, death
with a patent stent, stent dysfunction with a subsequent intervention i.e. repeated ERCP
or PTC = "objective stent failure", stent dysfunction, jaundice or cholangitis, but not
intervention has been undertaken due to a poor condition of the patient, "clinical stent
failure", the patient has undergone curative surgery or a bilio-enteric by-pass (a
gastro-enteroanastomosis or a duodenal stent is not a reason for exclusion), the patient
refuses further follow-up.
Detailed description:
Background
Malignancies causing distal malignant biliary obstruction may arise from the pancreas,
distal bile duct, the papilla of Vater or the duodenum. Pancreatic cancer is more common
with an incidence of 11.9/100,000/year, the other diagnoses account for 2.5/100,000/year,
thus a total incidence of some 14.4/100,000/year.
The above-mentioned tumors may cause occlusion of the bile duct with subsequent jaundice.
The liver function is impaired, and itching caused by the jaundice is disturbing. Only
15-20% of patients are suitable for curative surgery since symptoms often are vague, and
the diagnoses is delayed. Thus, at presentation the tumor may be locally advanced or
metastasized. High age and comorbidity may also make surgery impossible. Therefore,
therapy is often palliative not least aiming at relieving the jaundice.
The aim of stent treatment is to relieve the jaundice, and symptoms associated with the
bile duct occlusion. The ERCP-technique is in general the first choice in the biliary
intervention. The stenting may be complicated by dysfunction of the drainage, which may
be caused by stent occlusion by debris or tumor overgrowth/ingrowth, and stent migration
is not uncommon. A repeated biliary intervention is needed but may be difficult or even
impossible due to tumor progression. Thus, it is important that the stent treatment is
effective with a rapid relief of jaundice, and that the patency time is long.
Initially, plastic stents were used in the ERCP procedures, but now self-expandable metal
stents (SEMS) are more common. There are several randomized controlled trials (RCTs)
including one of our own group, and metanalyses showing that SEMS have a longer patency
time, and are more cost-effective than the plastic stents in the treatment of distal
malignant biliary obstruction. SEMS were initially made of steel but now nitinol alloys
are more commonly used and have been found superior having a longer patency time/less
rate of stent failure as demonstrated in a recent study. When first developed SEMS were
manufactured without a covering (uncovered, UC-SEMS) but in order to prevent tumor
ingrowth through the metal mesh SEMS were developed with a plastic covering, covered,
C-SEMS. The covering may include the whole length of the SEMS (fully covered, FC-SEMS) or
spare the 0.5-1 cm ends of the SEMS (semicovered, SC-SEMS).
There are several RCTs comparing UC-SEMS to SC-SEMS. Results are conflicting with some
RCTs demonstrating that SC-SEMS have a longer patency time whereas other have not
detected any difference between the two types of SEMS. FC-SEMS have been introduced more
recently with different outcomes as compared to UC-SEMS. There are no RCTs comparing
FC-SEMS to SC-SEMS and UC-SEMS.
UC-SEMS will often attach firmly to the tissue in the stricture, but tumor ingrowth may
impair stent function. The covering may prevent ingrowth but there is increased risk
migration. The bare proximal end of the SC-SEMS may decrease this risk but in analogy to
UC-SEMS they may attach firmly and preclude stent exchange. Contrarily, FC-SEMS may be
exchanged in case of dysfunction. Apart from tumor ingrowth and stent dislocation SEMS
dysfunction may be caused by proximal or distal overgrowth or epithelial hyperplasia on
the inside of the stent.
In conclusion, FC-SEMS may have advantages as compared to SC-SEMS or UC-SEMS, but these
three stent types have not been compared in RCTs.
Aim
The aim of the study is to investigate which type of SEMS is superior with respect to the
rate of stent failure and patency time (primary outcome). Also, the mechanisms behind the
stent failures are analyzed. The frequency and types of complications are studied, and
the patent survival time is recorded. The study is also exploring if there is a
difference in difficulty in the placement of the three types of stents.
Methods
The current study is a Swedish, three-armed randomized controlled multicenter trial
enrolling 450 patients. These patients with distal, malignant biliary obstruction are not
suitable for a radical resection (advanced/metastasized disease, comorbidity, high age)
are palliatively treated with SEMS. Patients have been investigated by multi-phase CT.
Palliative oncological therapy may also be used. After oral and written consent, the
patients are randomized to receive a single 10 mm in diameter UC-SEMS, SC-SEMS, or
FC-SEMS inserted at ERCP with a length of six or eight cm, multiple stenting is not
allowed. Randomization is performed at ERCP when the guide wire has passed the stenosis
in the bile duct. 150 patients are allocated to each arm using a randomization list and
sealed envelopes. Blocks of ten envelopes are distributed to the participating centers
and refilled on demand. The study has been approved by the Swedish Ethical Review
Authority (2017/416).
If the patient condition improves after stenting or the radiology after reevaluation
demonstrates that a resection is possible the patient will leave the study and proceed to
surgery. The placement of a SEMS in this situation as a temporary biliary drainage,
before a resection, is no disadvantage. Contrarily, with the superior function of a SEMS
as compared to a plastic stent a more rapid biliary relief without early stent failure is
accomplished without making surgery more difficult. Thus, it is acceptable that
occasional patients are included in a palliative setting, and after reevaluation may
proceed to surgery.
The statistical calculations have been performed by the Uppsala Clinical Research Center,
UCR. According to the power calculation a difference in stent failure of 14% may be
detected with a power of 80%, alpha =0.05, if 150 patients are included in each study
arm. A smaller difference in not judged to be clinically significant. The inclusion time
is estimated to be three years, and the follow-up time is 12 months.
There are thirteen participating hospitals, seven university hospitals, and six other
major hospitals. The participating centers are:
University hospital in Uppsala, Karolinska university hospital in Huddinge, University
hospital in Örebro, University hospital in Lund, University hospital in Malmö,
Sahlgrenska University hospital in Gothenburg, University hospital in Umeå, South
hospital in Stockholm, Danderyds hospital in Stockholm, Capio S:t Görans hospital in
Stockholm, Skaraborgs hospital in Skövde, Central hospital in Västerås, Central hospital
in Karlstad.
Inclusion
1. Obstructive jaundice (S-Bilirubin > 50 μmol /L). Initial treatment according to the
local routine, laboratory test, abdominal CT, often a thoracic CT, and US. These
investigations along with the clinical information support the finding of a distal
malignant occlusion, and an ERCP is performed.
2. The ERCP demonstrates a seemingly malignant distal biliary stenosis located more
than 2 cm below the hilum of the liver.
3. The patient has been found not suitable for curative surgery having a locally to
advanced tumor (not a candidate for down-staging) or metastatic decease. The patient
age and comorbidity may also preclude major surgery. If the investigations and
evaluation is not complete at the time of the ERCP it is permitted to place a
temporary plastic endoprosthesis.
4. Patient information. The study has been approved by the Swedish Ethical Review
Authority (2017/416) as a multicenter study including an approval for all of the
participating centers. The approval of the patient may be withdrawn during the
course of the study and will not affect the further treatment which is carried out
according to the routine of the participating clinic.
5. Randomization. If the patient has agreed to participate in the study the
randomization is performed at the ERCP procedure when the biliary tract has been
cannulated, and the guide wire has passed the stenosis. The patient is allocated to
UC SEMS, SC, or FC SEMS by the method of sealed, opaque envelopes.
Endpoint of follow-up -12 months - is when/if:
1. The patient has been followed >12 months with a patent stent.
2. The patient expires with a patent stent <12 months.
3. The patient has been found resectable and undergone curative surgery or a
bilio-enteric by-pass (a gastro-enteroanastomosis or a duodenal stent is not a
reason for exclusion).
4. Stent dysfunction with a subsequent intervention i.e. repeated ERCP or PTC =
"objective stent failure".
5. Stent dysfunction, jaundice or cholangitis, but not intervention has been undertaken
due to a poor condition of the patient, "clinical stent failure" is also an
endpoint.
6. The patient refuses further follow-up.
Follow-up
There is a follow-up 1 month after the ERCP/randomization including laboratory tests, and
if the patient condition permits, also a visit at the out-patient clinic. The following
monthly checks are performed by phone with questions regarding symptoms of stent
dysfunction.
Significance
If one stent type is superior it should be recommended for further use. If the stents are
equal there is an argument for inserting only FC SEMS since they also can be extracted,
and replaced when occluded, which may be a better alternative than stent in stent
placement (plastic endoprosthesis or SEMS). Parallel to the evolvement of new oncological
strategies there will probably be a demand for SEMS extraction or replacement i.e. radio
frequency, irreversible electroporation, or photodynamic treatment. Moreover, in a
situation when a benign condition cannot be excluded the option of a SEMS removal is
important. The storage of SEMS in the endoscopy units will also be simplified, and
cheaper if there is only need for one type of SEMS.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patient age > 20 years.
- The biliary stenosis located > 2 cm below the hilum of the liver, and with a
malignant appearance.
- The patient history, and clinical data supporting a malignant bile duct stenosis.
- S-Bilirubin > 50 μmol/L.
- Curative surgery or down-staging not possible due to an advanced decease, or surgery
is precluded by high age or co-morbidity. Temporary placement of a plastic
endoprosthesis allowed, and after reevaluation within 4 weeks the patient may enter
the study.
- The patient has received oral and written information about the study and accepted
to participate.
- CT and/or Ultrasound has been performed.
Exclusion Criteria:
- Informed consent has not been obtained or denied.
- The presence of significant intrahepatic stenoses caused by metastatic disease with
also intrahepatic obstruction of the bile flow. A malignant stenosis in the hilum of
the liver, or a tumor stricture located < 2cm below the hilum of the liver.
- The patient is probably a candidate for curative surgery or down-staging.
- Suspicion of a benign biliary obstruction.
- Anatomical situation making ERCP impossible i.e. prior surgical interventions or a
tumor stenosis of the duodenum. If the ERCP is not successful at the first attempt a
repeated procedure or a PTC rendezvouz is allowed within one week.
- Prior biliary drainage (> 4 weeks earlier).
- Increased risk of bleeding (INR >1.5)
- The patient has previously been included in the study.
Gender:
All
Minimum age:
20 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Danderyds hospital
Address:
City:
Danderyd
Zip:
18288
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Farshad Frozanpor, MD, PhD
Phone:
+760499415
Email:
farshad.frozanpor@regionstockholm.se
Facility:
Name:
Sahlgrenska University hospital
Address:
City:
Gothenburg
Zip:
413 45
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Riadh Sadik, MD, PhD
Phone:
+46313427387
Email:
riadh.sadik@vgregion.se
Facility:
Name:
Central Hospital Karlstad
Address:
City:
Karlstad
Zip:
652 40
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Joen Ståhlbröst, MD
Phone:
+46108315335
Email:
joen.stahlbrost@regionvarmland.se
Facility:
Name:
University Hospital Lund
Address:
City:
Lund
Zip:
222 42
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Emma Nilsson, MD, PhD
Phone:
+4646177706
Email:
emma.nilsson@med.lu.se
Facility:
Name:
University Hospital Malmö
Address:
City:
Malmö
Zip:
214 28
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Gabriele Wurm Johansson, MD, PhD
Phone:
+4640338613
Email:
Gabriele.WurmJohansson@skane.se
Facility:
Name:
Skaraborgs Hospital Skövde
Address:
City:
Skövde
Zip:
549 49
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Erik Haraldsson, MD, PhD
Phone:
+46709390786
Email:
erik.haraldsson@vgregion.se
Facility:
Name:
Capio S:t Görans hospital
Address:
City:
Stockholm
Zip:
112 19
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Rikard Henricsson, MD, PhD
Phone:
+46707662065
Email:
rikard.henricsson@capiostgoran.se
Facility:
Name:
Stockholm South Hospital
Address:
City:
Stockholm
Zip:
118 83
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Emma Sverén, MD, PhD
Phone:
+46725993731
Email:
emma.sverden@regionstockholm.se
Facility:
Name:
University Hospital of Umeå
Address:
City:
Umeå
Zip:
901 85
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Petter Sellberg, MD, PhD
Phone:
+46702259598
Email:
petter.sellberg@regionvasterbotten.se
Facility:
Name:
University hospital Uppsala
Address:
City:
Uppsala
Zip:
751 85
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Eva Lena Syrén, MD, PhD
Phone:
+46703629034
Email:
eva.lena.syren@akademiska.se
Facility:
Name:
Central Hospital Västerås
Address:
City:
Västerås
Zip:
721 89
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Maria Johansson, MD
Phone:
+4621173337
Email:
maria.x.johansson@regionvastmanland.se
Facility:
Name:
University Hospital Örebro
Address:
City:
Örebro
Zip:
701 85
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Malin Wickbom, MD, PhD
Phone:
+46196021000
Email:
malin.wickbom@regionorebrolan.se
Start date:
February 4, 2020
Completion date:
January 15, 2026
Lead sponsor:
Agency:
Region Stockholm
Agency class:
Other
Source:
Region Stockholm
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06453590
https://www.socialstyrelsen.se/globalassets/sharepoint-dokument/dokument-webb/statistik/cancer-i-siffror-2023.pdf
