Ignite Creation Date:
2024-06-16 @ 11:52 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06453590
Status:
RECRUITING
Last Update Posted:
2024-06-11
First Post:
2024-05-28
Brief Title:
Treatment of Distal Malignant Biliary Obstruction by Uncovered Partially Covered or Fully Covered Metal Stents
Sponsor:
Region Stockholm
Organization:
Region Stockholm
Study Overview
Official Title:
Palliative Treatment of Distal Malignant Biliary Obstruction by Endoscopic Stents Uncovered Partially Covered or Fully Covered Metal Stents A Prospective Randomized Multicenter Study
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 ie 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
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 ie 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 119100000year the other diagnoses account for 25100000year thus a total incidence of some 144100000year
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 overgrowthingrowth 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 timeless 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 05-1 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 impaire 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 advancedmetastasized 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 2017416
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 Cavell et al 2013 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 005 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 St 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 2017416 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 whenif
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 ie 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 ERCPrandomization 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 ie 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
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 119100000year the other diagnoses account for 25100000year thus a total incidence of some 144100000year
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 overgrowthingrowth 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 timeless 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 05-1 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 impaire 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 advancedmetastasized 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 2017416
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 Cavell et al 2013 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 005 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 St 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 2017416 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 whenif
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 ie 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 ERCPrandomization 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 ie 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None