Chronic Pancreatitis
Conditions
Brief summary
To prospectively document the performance of a FCSEMS for treatment of pancreatic duct strictures in patients with painful chronic pancreatitis.
Detailed description
This study is a prospective, single arm, pre-approval study. Treatment of up to 92 patients will take place at up to 15 clinical centers. Patient who meet all eligibility criteria will receive the WallFlex Pancreatic stent for up to 6 months stent indwell and 6 months follow-up after stent removal.
Interventions
DEVICEPancreatic fully-covered self-expanding metal stent (FCSEMS)
The WallFlex™ Pancreatic RX Fully Covered Soft Stent System consists of a flexible delivery system preloaded with a self-expanding pancreatic metal stent.
Sponsors
Boston Scientific Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 or older * Willing and able to comply with study procedures and follow-up schedule and provide written informed consent to participate in study * Chronic pancreatitis induced stricture of Cremer Type IV, namely distal dominant stricture with upstream ductal dilation. * For patients with one prior plastic pancreatic stent: VAS Pain Score and Frequency of Pain sectors of the Izbicki pain scale at the time of placement of the plastic stent. * Availability of narcotic dosage for at least one month prior to baseline visit for patients who do not have a prior plastic stent or availability for one month prior to placement of prior plastic stent, where applicable. * VAS Pain Score of ≥ 20 before study stent placement for patients without a prior plastic pancreatic stent. VAS Pain Score of ≥ 20 before initial plastic pancreatic stent placement for patients with a prior plastic pancreatic stent indwelling for 90 days or less before study stent placement. VAS Pain Score is captured via Izbicki pain scale. * Pain occurring weekly or more frequently (assessed by Frequency of Pain sector of the Izbicki pain scale) as reported before study stent placement for patients without a prior plastic pancreatic stent, or before placement of initial plastic pancreatic stent for patients with a prior plastic pancreatic stent indwelling for 90 days or less before study stent placement. * Minimum 5 mm diameter of dilated duct immediately upstream of pancreatic duct stricture * Prior clearance of pancreatic stones where needed * If pancreatic duct stone clearance prior to placement of the study stent includes ESWL, then a plastic pancreatic stent may be placed immediately after the ESWL procedure at the discretion of the Investigator, for example, if there is concern about stone fragments of stone sludge in side branches of the pancreatic duct, and may be left indwelling for 30-90 days. * If new pancreatic duct stones requiring ESWL have formed by the time of intended study stent placement, then the patient will not receive the study stent and be excluded from the study. Further treatment of the patient will be provided per standard of practice outside of the study. In case the study stent is not placed during the same session in which the plastic stent is removed, the pain score needs to be collected again prior to study stent placement. * Prior endoscopic pancreatic sphincterotomy (EPS), historically or to be provided at time of SEMS placement as applicable.
Exclusion criteria
* Pancreatic or peri-ampullary cancer with or without pancreatic duct strictures caused by malignancy * Biliary strictures caused by chronic pancreatitis that are symptomatic and/or in need of therapeutic intervention * Perforated duct * Ansa pancreatica * Presence of pancreatic cysts suspected to be cystic tumor or requiring transmural drainage * Duodenal/groove pancreatitis * Autoimmune pancreatitis * Pancreatic duct stenoses not located in the head of the pancreas * Failed access during an attempted ERCP on a prior date at the investigational center * Duration of indwell of one single plastic pancreatic stent or cumulative duration of consecutive single plastic pancreatic stents immediately prior to study stent placement exceeding 90 days * History of prior single pancreatic plastic stent(s) followed by a stent-free period shorter than 1 year before enrollment into the study * History of prior side-by-side multiple pancreatic plastic stents up to one year prior to enrollment * History of prior pancreatic metal stent(s) * Reported recent history of acute relapsing pancreatitis in the absence of chronic pancreatitis * Patients for whom endoscopic techniques are contraindicated * Patients who are currently enrolled in another investigational study that would directly interfere with the current study, without prior written approval from the sponsor * Inability or refusal to comply with the follow-up schedule including patients living at such a distance from the investigational center that attending follow-up visits would be unusually difficult or burdensome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Reduction | Baseline to 6 months post-stent removal or 6 months post-observation of complete or partial stent migration | The self-reported pain score (0-100) was the mean of the Visual Analogue Scale (VAS) and Izbicki Frequency of Pain subscore (sum treated as a continuous variable).The primary efficacy endpoint was the proportion of patients who had complete (pain score ≤ 10) or partial (pain score ˃ 10 but reduced at least 50% compared to pain as baseline) pain relief by 6 months after FCSEMS removal or observation of CDM or partial stent migration. Primary efficacy endpoint failure included any of the following: 1) no pain relief, 2) complete or partial pain relief in the setting of a 50% higher average daily narcotic dose compared to the patient's daily average narcotic dose in the month prior to baseline and at 6 months post-stent removal/observation of CDM, 3) stent migration in setting of recurring pain (VAS Pain Score of ≥ 20), 4) restenting in the setting of recurring pain. |
| Rate of Related SAEs From WallFlex Pancreatic Stent Placement to End of Study | Baseline to 6 months post-stent removal or 6 months post-observation of complete or partial stent migration | The primary safety endpoint was the rate of serious adverse events (SAEs) related to the FCSEMS or study procedures from FCSEMS placement to end of study follow-up. Pain thought to be caused by FCSEMS pancreatic stent expansion was reported but did not count towards the endpoint if all three of the following conditions applied: 1. Pain managed by medication, with the exception of injectable narcotic use for more than 24 hours. 2. Pain not causing pancreatic FCSEMS removal. 3. Pain resolved by 72 hours after pancreatic FCSEMS placement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stent Migration Rate | Study stent placement through 6 months post-stent removal or 6 months post-observation of complete or partial stent migration | Stent migration is the change in location of a stent from its originally placed location. In this study, pancreatic stent migration was noted as partial or complete and either proximal (i.e., into the pancreas) or distal (i.e., out of the pancreas). |
| Stent Placement Success | Assessed upon study stent placement. This endpoint is assessed at the Study Stent Placement visit (Day 0). | Satisfactory position is defined as the stent being across the stricture, without visible occluding impaction at the genu of the pancreatic duct and with distal end of the stent visible in the duodenum. |
| Secondary Stricture Rate | Study stent placement through 6 months post-stent removal or 6 months post-observation of complete or partial stent migration | A secondary stricture is a ductal narrowing located at the intraductal edge of the study stent. |
| Restenting Rate | Study stent removal or observation of study stent migration through 6 months post-stent removal or 6 months post-observation of complete or partial stent migration | Restenting is the placement of a non-study stent due to no improvement in clinical status and associated persistence of stricture following removal or complete distal migration of the study stent. |
| Endoscopic Stent Removal Success | Assessed at study stent removal or observation of complete or partial stent migration. This is endpoint is assessed through the Month 6 Study Stent Removal visit. | Endoscopic stent removal success is defined as ability to remove stent endoscopically (forceps, snare) without serious stent removal-related adverse events. |
Countries
Belgium, Canada, India, Italy, Netherlands, United States
Participant flow
Pre-assignment details
Participants were considered enrolled after providing written informed consent. Participants who provided written informed consent but subsequently did not meet one or more of the selection criteria were considered screen failures and excluded from the study. Only participants who met all eligibility criteria were counted toward the enrollment ceiling and considered the primary analysis cohort.
Participants by arm
| Arm | Count |
|---|---|
| WallFlex FCSEMS Recipients The WallFlex™ Pancreatic RX Fully Covered Soft Stent System consists of a flexible delivery system preloaded with a self-expanding pancreatic metal stent. Patients who meet all eligibility criteria will receive the WallFlex Pancreatic stent for up to 6 months stent indwell and 6 months follow-up after stent removal. A patient is considered enrolled after signing the study-specific Informed Consent Form (ICF). Patients who sign the ICF but subsequently do not meet one or more of the selection criteria will be considered screen failures and excluded from the study.
Pancreatic fully-covered self-expanding metal stent (FCSEMS): The WallFlex™ Pancreatic RX Fully Covered Soft Stent System consists of a flexible delivery system preloaded with a self-expanding pancreatic metal stent. | 67 |
| Total | 67 |
Baseline characteristics
| Characteristic | WallFlex FCSEMS Recipients |
|---|---|
| Age, Continuous | 52.7 years STANDARD_DEVIATION 12.5 |
| CP Calcific No | 18 Participants |
| CP Calcific Unknown | 1 Participants |
| CP Calcific Yes | 48 Participants |
| CP Etiology Alcoholic | 33 Participants |
| CP Etiology Gallstones | 1 Participants |
| CP Etiology Hereditary | 3 Participants |
| CP Etiology Other | 8 Participants |
| CP Etiology Smoking | 24 Participants |
| CP Etiology Unknown | 19 Participants |
| Current Alcohol Consumption | 8 Participants |
| Current Pancreatic Stones | 42 Participants |
| Diabetes Status Insulin Dependent | 20 Participants |
| Diabetes Status Oral Medication | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| History of Pancreatic Duct Stones Unknown | 4 Participants |
| History of Pancreatic Duct Stones Yes | 37 Participants |
| Largest Stone | 6.2 millimeter STANDARD_DEVIATION 3.9 |
| Narcotic Dose | 31.9 morphine milligram equivalents STANDARD_DEVIATION 52.3 |
| Pancreas Divisum | 18 Participants |
| Prior Biliary or Pancreatic Sphincterotomy Performed | 48 Participants |
| Prior Pancreatic Sphincterotomy Performed | 47 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 54 Participants |
| Region of Enrollment Belgium | 9 Participants |
| Region of Enrollment India | 7 Participants |
| Region of Enrollment Italy | 7 Participants |
| Region of Enrollment United States | 44 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 42 Participants |
| Smoking Status Current | 36 Participants |
| Smoking Status Never | 14 Participants |
| Smoking Status Previous | 17 Participants |
| Steatorrhea | 13 Participants |
| Stone Clearance Procedures Performed Balloon | 20 Participants |
| Stone Clearance Procedures Performed Basket | 5 Participants |
| Stone Clearance Procedures Performed ESWL | 16 Participants |
| Stone Clearance Procedures Performed Other | 1 Participants |
| Surgical Candidate No | 12 Participants |
| Surgical Candidate Unknown | 9 Participants |
| Surgical Candidate Yes | 46 Participants |
| Time Since CP Diagnosed | 6.4 years STANDARD_DEVIATION 6.4 |
| Time Since First Narcotic Medication | 4.8 years STANDARD_DEVIATION 7.3 |
| Type of Calcification Both | 19 Participants |
| Type of Calcification Ductal | 20 Participants |
| Type of Calcification Parenchymal | 9 Participants |
| Weight | 71.5 kilograms STANDARD_DEVIATION 18.4 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 67 |
| other Total, other adverse events | 20 / 67 |
| serious Total, serious adverse events | 21 / 67 |
Outcome results
Primary
Pain Reduction
The self-reported pain score (0-100) was the mean of the Visual Analogue Scale (VAS) and Izbicki Frequency of Pain subscore (sum treated as a continuous variable).The primary efficacy endpoint was the proportion of patients who had complete (pain score ≤ 10) or partial (pain score ˃ 10 but reduced at least 50% compared to pain as baseline) pain relief by 6 months after FCSEMS removal or observation of CDM or partial stent migration. Primary efficacy endpoint failure included any of the following: 1) no pain relief, 2) complete or partial pain relief in the setting of a 50% higher average daily narcotic dose compared to the patient's daily average narcotic dose in the month prior to baseline and at 6 months post-stent removal/observation of CDM, 3) stent migration in setting of recurring pain (VAS Pain Score of ≥ 20), 4) restenting in the setting of recurring pain.
Time frame: Baseline to 6 months post-stent removal or 6 months post-observation of complete or partial stent migration
Population: There were 67 participants who enrolled in the study and had attempted FCSEMS placement. Of the 67 participants with attempted FCSEMS placement, 21 were excluded because they were not eligible for the primary efficacy endpoint analysis (i.e., 16 had insufficient pain, 2 died, and 3 were lost to follow-up). As a result, 46 participants were eligible for the primary efficacy endpoint analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| WallFlex FCSEMS Recipients | Pain Reduction | 12 Participants |
Comparison: We hypothesized that pain reduction (as defined in Study endpoints above) would be achieved in a performance goal of at least 53% of patients receiving the study SEMS. Assuming an observed pain reduction rate of 75% and using an exact test with a one-sided alpha of 0.025, 43 patients were required to obtain power of at least 80%.p-value: 0.999Fisher Exact
Primary
Rate of Related SAEs From WallFlex Pancreatic Stent Placement to End of Study
The primary safety endpoint was the rate of serious adverse events (SAEs) related to the FCSEMS or study procedures from FCSEMS placement to end of study follow-up. Pain thought to be caused by FCSEMS pancreatic stent expansion was reported but did not count towards the endpoint if all three of the following conditions applied: 1. Pain managed by medication, with the exception of injectable narcotic use for more than 24 hours. 2. Pain not causing pancreatic FCSEMS removal. 3. Pain resolved by 72 hours after pancreatic FCSEMS placement.
Time frame: Baseline to 6 months post-stent removal or 6 months post-observation of complete or partial stent migration
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| WallFlex FCSEMS Recipients | Rate of Related SAEs From WallFlex Pancreatic Stent Placement to End of Study | 21 Participants |
p-value: 0.513Fisher Exact
Secondary
Endoscopic Stent Removal Success
Endoscopic stent removal success is defined as ability to remove stent endoscopically (forceps, snare) without serious stent removal-related adverse events.
Time frame: Assessed at study stent removal or observation of complete or partial stent migration. This is endpoint is assessed through the Month 6 Study Stent Removal visit.
Population: There were 67 participants who enrolled in the study and had attempted FCSEMS placement. Technical success (i.e., successful stent placement) was achieved in 65 of the 67 participants with attempted FCSEMS placement. As a result, 65 participants were evaluated for the endoscopic stent removal success endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| WallFlex FCSEMS Recipients | Endoscopic Stent Removal Success | 63 Participants |
Secondary
Restenting Rate
Restenting is the placement of a non-study stent due to no improvement in clinical status and associated persistence of stricture following removal or complete distal migration of the study stent.
Time frame: Study stent removal or observation of study stent migration through 6 months post-stent removal or 6 months post-observation of complete or partial stent migration
Population: There were 67 participants who enrolled in the study and had attempted FCSEMS placement. Technical success (i.e., successful stent placement) was achieved in 65 of the 67 participants with attempted FCSEMS placement. As a result, 65 participants were evaluated for the restenting rate endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| WallFlex FCSEMS Recipients | Restenting Rate | 11 Participants |
Secondary
Secondary Stricture Rate
A secondary stricture is a ductal narrowing located at the intraductal edge of the study stent.
Time frame: Study stent placement through 6 months post-stent removal or 6 months post-observation of complete or partial stent migration
Population: There were 67 participants who enrolled in the study and had attempted FCSEMS placement. Technical success (i.e., successful stent placement) was achieved in 65 of the 67 participants with attempted FCSEMS placement. As a result, 65 participants were evaluated for the secondary stricture rate endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| WallFlex FCSEMS Recipients | Secondary Stricture Rate | 5 Participants |
Secondary
Stent Migration Rate
Stent migration is the change in location of a stent from its originally placed location. In this study, pancreatic stent migration was noted as partial or complete and either proximal (i.e., into the pancreas) or distal (i.e., out of the pancreas).
Time frame: Study stent placement through 6 months post-stent removal or 6 months post-observation of complete or partial stent migration
Population: There were 67 participants who enrolled in the study and had attempted FCSEMS placement. Technical success (i.e., successful stent placement) was achieved in 65 of the 67 participants with attempted FCSEMS placement. As a result, 65 participants were evaluated for the stent migration endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| WallFlex FCSEMS Recipients | Stent Migration Rate | 31 Participants |
Secondary
Stent Placement Success
Satisfactory position is defined as the stent being across the stricture, without visible occluding impaction at the genu of the pancreatic duct and with distal end of the stent visible in the duodenum.
Time frame: Assessed upon study stent placement. This endpoint is assessed at the Study Stent Placement visit (Day 0).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| WallFlex FCSEMS Recipients | Stent Placement Success | 65 Participants |