Biliary Stricture
Conditions
Keywords
benign biliary strictures secondary to chronic pancreatitis
Brief summary
The purpose of this of this study is to compare the use of Self Expanding Metal Stents (SEMS) to plastic stents for the treatment of benign biliary strictures secondary to chronic pancreatitis as it pertains to stricture resolution rates, complication rates and number of endoscopic retrograde cholangiopancreatography (ERCP) procedures during 24 months. Statistical testing will be performed to determine if the rate of stricture resolution for the metal stent is non-inferior to the plastic stent group.
Interventions
Temporary placement of the WallFlex Biliary RX Fully Covered Stent for treatment of benign biliary strictures secondary to chronic pancreatitis. The stent will be removed after 12 months indwell. (RMV in intervention name indicates removable)
DEVICECommercially available Plastic Stent Per Investigator preference
Temporary placement/exchange of multiple biliary plastic stents for treatment of benign biliary strictures secondary to chronic pancreatitis. Stents will be removed after cumulative indwell of 12 months.
Sponsors
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age 18 or older * Willing and able to comply with the study procedures and provide written informed consent to participate in the study * Chronic pancreatitis * Symptomatic bile duct stricture (defined by cholangitis or persistent jaundice for at least one month or cholestasis associated with at least 3 times normal alkaline phosphatase levels) documented at time of enrollment for naïve stricture or at the time of prior plastic stent placement in strictures that had one prior plastic stent inserted.12 * Common bile duct stricture based on imaging assessment of dilatation of the common and/or intrahepatic bile ducts
Exclusion criteria
* Biliary stricture of benign etiology other than chronic pancreatitis * Prior biliary metal stent or any plastic stenting other than one plastic stent of 10 Fr or less for 6 months or fewer * Developing obstructive biliary symptoms associated with an attack of acute pancreatitis * Biliary stricture of malignant etiology * Stricture within 2 cm of common bile duct bifurcation * Known bile duct fistula or leak * Subjects for whom endoscopic techniques are contraindicated * Known sensitivity to any components of the stent or delivery system * Symptomatic duodenal stenosis (with gastric stasis) * Participation in another investigational study within 90 days prior to consent * Investigator Discretion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Stricture Resolution | After 12-month stenting period through 24 month follow-up (approximately 12 months) | Stricture resolution defined as absence of re-stenting after the 12-month stenting period, and 24 months serum alkaline phosphatase level not exceeding twice the level at the end of stenting period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Events Related to the Device or Procedure | Initial stent placement procedure to 24 month follow-up | Device or procedure related serious adverse events from the initial stent placement procedure to the 24 month follow-up. |
| Number of ERCP Procedures Through 24 Months After Initial Stent Placement. | Initial stent placement procedure to 24 month follow-up | The number of endoscopic retrograde cholangiopancreatography (ERCP) procedures through 24 months, after initial stent placement. |
| Ability to Deploy Stent(s) in Satisfactory Position (Technical Success) | Initial stent placement procedure | Technical success defined as the ability to deploy the stent(s) in satisfactory position during initial stent placement procedure. |
| Length of Stent Placement and Removal Procedures | Initial stent placement procedure to 24 month follow-up | Length of stent placement procedures and stent removal procedures. |
| Number of Stents Placed | Initial stent placement procedure to 24 month follow-up | Number of stents placed throughout study to 24 month follow-up |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Hong Kong, India, Italy, Netherlands, Sweden
Participant flow
Pre-assignment details
Of 172 enrolled participants, 164 met inclusion criteria and were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Metal Stents The WallFlex Biliary Fully Covered Stent System is being evaluated for treatment of benign biliary strictures secondary to chronic pancreatitis.
WallFlex™ Biliary RX Fully Covered Stent System RMV: Temporary placement of the WallFlex Biliary RX Fully Covered Stent for treatment of benign biliary strictures secondary to chronic pancreatitis. The stent will be removed after 12 months indwell. | 80 |
| Plastic Stents Plastic stents per Investigator preference are being evaluated for treatment of benign biliary strictures secondary to chronic pancreatitis.
Commercially available Plastic Stent Per Investigator preference: Temporary placement/exchange of multiple biliary plastic stents for treatment of benign biliary strictures secondary to chronic pancreatitis. Stents will be removed after cumulative indwell of 12 months. | 84 |
| Total | 164 |
Baseline characteristics
| Characteristic | Metal Stents | Plastic Stents | Total |
|---|---|---|---|
| Age, Continuous | 51 years | 53 years | 52 years |
| Baseline Alkaline Phosphatase | 337 IU/L | 262.5 IU/L | 299 IU/L |
| Baseline Bilirubin | 1 mg/dL | 1.4 mg/dL | 1.3 mg/dL |
| Calcifying CP | 59 Participants | 62 Participants | 121 Participants |
| Candidate for surgery | 60 Participants | 61 Participants | 121 Participants |
| CP etiology alcoholic | 54 Participants | 53 Participants | 107 Participants |
| Gallbladder in situ | 69 Participants | 72 Participants | 141 Participants |
| Prior Biliary Sphincterotomy | 39 Participants | 39 Participants | 78 Participants |
| Prior pancreatic sphincterotomy | 26 Participants | 27 Participants | 53 Participants |
| Prior plastic stent | 34 Participants | 38 Participants | 72 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Australia | 4 participants | 3 participants | 7 participants |
| Region of Enrollment Austria | 8 participants | 11 participants | 19 participants |
| Region of Enrollment Belgium | 13 participants | 13 participants | 26 participants |
| Region of Enrollment Canada | 2 participants | 3 participants | 5 participants |
| Region of Enrollment France | 6 participants | 6 participants | 12 participants |
| Region of Enrollment Germany | 1 participants | 1 participants | 2 participants |
| Region of Enrollment Hong Kong | 2 participants | 3 participants | 5 participants |
| Region of Enrollment India | 20 participants | 20 participants | 40 participants |
| Region of Enrollment Italy | 16 participants | 16 participants | 32 participants |
| Region of Enrollment Netherlands | 5 participants | 6 participants | 11 participants |
| Region of Enrollment Sweden | 3 participants | 2 participants | 5 participants |
| Sex: Female, Male Female | 10 Participants | 12 Participants | 22 Participants |
| Sex: Female, Male Male | 70 Participants | 72 Participants | 142 Participants |
| Time since chronic pancreatitis (CP) diagnosed | 3.1 years | 1.7 years | 1.9 years |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 80 | 3 / 84 |
| other Total, other adverse events | 3 / 80 | 8 / 84 |
| serious Total, serious adverse events | 19 / 80 | 16 / 84 |
Outcome results
Primary
Number of Participants With Stricture Resolution
Stricture resolution defined as absence of re-stenting after the 12-month stenting period, and 24 months serum alkaline phosphatase level not exceeding twice the level at the end of stenting period.
Time frame: After 12-month stenting period through 24 month follow-up (approximately 12 months)
Population: Of 80 participants in metal stent arm, only 62 were eligible for primary endpoint evaluation. Of 84 participants in plastic stent arm, only 70 were eligible for primary endpoint evaluation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metal Stents | Number of Participants With Stricture Resolution | 47 Participants |
| Plastic Stents | Number of Participants With Stricture Resolution | 54 Participants |
p-value: 0.008Exact non-inferiority
Secondary
Ability to Deploy Stent(s) in Satisfactory Position (Technical Success)
Technical success defined as the ability to deploy the stent(s) in satisfactory position during initial stent placement procedure.
Time frame: Initial stent placement procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metal Stents | Ability to Deploy Stent(s) in Satisfactory Position (Technical Success) | 79 Participants |
| Plastic Stents | Ability to Deploy Stent(s) in Satisfactory Position (Technical Success) | 82 Participants |
p-value: 0.99Fisher Exact
Secondary
Length of Stent Placement and Removal Procedures
Length of stent placement procedures and stent removal procedures.
Time frame: Initial stent placement procedure to 24 month follow-up
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Metal Stents | Length of Stent Placement and Removal Procedures | 26 minutes |
| Plastic Stents | Length of Stent Placement and Removal Procedures | 28 minutes |
p-value: 0.519Wilcoxon (Mann-Whitney)
Secondary
Number of ERCP Procedures Through 24 Months After Initial Stent Placement.
The number of endoscopic retrograde cholangiopancreatography (ERCP) procedures through 24 months, after initial stent placement.
Time frame: Initial stent placement procedure to 24 month follow-up
Population: Of 80 participants in metal stent arm, 1 participant failed technical success at baseline and did have a completed ERCP procedure. Of 84 participants in plastic stent arm, 2 participants failed technical success at baseline and did have a completed ERCP procedure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metal Stents | Number of ERCP Procedures Through 24 Months After Initial Stent Placement. | 2.6 procedures | Standard Deviation 1.3 |
| Plastic Stents | Number of ERCP Procedures Through 24 Months After Initial Stent Placement. | 3.9 procedures | Standard Deviation 1.3 |
p-value: <0.001Negative binomial
Secondary
Number of Stents Placed
Number of stents placed throughout study to 24 month follow-up
Time frame: Initial stent placement procedure to 24 month follow-up
Population: Of 80 participants in metal stent arm, 1 participant never had a stent placed. Of 84 participants in plastic stent arm, 2 participants never had a stent placed, 1 participant withdrew from the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metal Stents | Number of Stents Placed | 2.3 number of stents | Standard Deviation 3.3 |
| Plastic Stents | Number of Stents Placed | 6.7 number of stents | Standard Deviation 4.4 |
p-value: <0.001Negative binomial
Secondary
Serious Adverse Events Related to the Device or Procedure
Device or procedure related serious adverse events from the initial stent placement procedure to the 24 month follow-up.
Time frame: Initial stent placement procedure to 24 month follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metal Stents | Serious Adverse Events Related to the Device or Procedure | 19 Participants |
| Plastic Stents | Serious Adverse Events Related to the Device or Procedure | 16 Participants |
p-value: 0.568Fisher Exact