Inoperable Tumors of the Bile Duct
Conditions
Brief summary
The purpose of the study is to determine the best management of bile duct narrowing (stricture) due to inoperable tumors. The bile duct is a tube that carries bile formed in the liver to the small bowel to digest fats. Tumors around the bile duct can compress the duct causing pain, jaundice (yellow skin and eyes), itchy skin and fever.
Detailed description
This is a prospective randomized trial conducted at 4 large teaching hospitals (Brigham and Women's Hospital, Massachusetts General Hospital, and Boston Medical Center, Boston, Massachusetts, and Mayo Clinic, Rochester, Minnesota). Malignancy is determined by pathology. Cancer stage is determined by transabdominal imaging and/or endoscopic ultrasound (EUS). Written informed consent is obtained from each of the enrolled patients. The study is approved by the Institutional Review Boards at each of the participating centers.
Interventions
DEVICEPartially Covered Wallstent
Partially covered wallstent
DEVICEUncovered Wallstent
Uncovered wallstent
Sponsors
Boston Scientific Corporation
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years of age. * Malignant bile duct stricture. * Increased bilirubin. * Duct stricture is ≥ 1 cm distal to the biliary hilum (bifurcation of the common hepatic duct into the right and left hepatic ducts). * Not an operative candidate.
Exclusion criteria
* Unable to obtain consent. * Unable to tolerate procedure. * Suspected benign bile duct stricture. * Candidate for potentially curative surgical intervention. * Previous metallic biliary stent. * Previous bile duct surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Recurrent Biliary Obstruction | Median follow-up of 125 days in the uncovered SEMS arm and 201 days in the partially covered SEMS arm | Biliary obstruction is the narrowing (stricture) of the bile duct. This narrowing prevents bile, which is formed in the liver, from being carried to the small bowel to digest fats. Symptoms of biliary obstruction are pain, jaundice (yellow skin and eyes), itchy skin and fever. Time to biliary obstruction is defined as the time from the placement of the stent to the time of biliary obstruction as reported by the participant via monthly interview questions or call to a pager if symptoms of recurrent biliary obstruction developed. Participants not experiencing recurrent biliary obstruction were censored at the date of last follow-up or date of death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Survival | Median follow-up of 125 days in the uncovered SEMS arm and 201 days in the partially covered SEMS arm | Patient survival is defined as the date of the placement of the stent to the date of death. Participants lost to follow-up were analyzed in an intention-to-treat fashion and censored at the time of their last follow-up interview. |
| Number of Participants With Serious Adverse Events (SAEs) | From time of stent placement to participant death or lost to follow-up (up to 1302 days) | Serious adverse events were defined as adverse events requiring an invasive procedure or hospitalization or resulting in death. |
| Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism | Median follow-up of 125 days in the uncovered SEMS arm and 201 days in the partially covered SEMS arm | Mechanisms of recurrent biliary obstructions are defined as tumor ingrowth, tumor overgrowth, stent migration, sludge, food debris, stent failed to expand and unknown. Stents may be obstructed by more than one mechanism, therefore, the total does not add up to the number of stent obstructions in each group. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Uncovered Wallstent Endoscopically-placed biliary self-expanding metal stent (SEMS) (uncovered type). | 61 |
| Partially Covered Wallstent Endoscopically-placed biliary self-expanding metal stent (SEMS) (partially covered type). | 68 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Died Unobstructed | 38 | 41 |
| Overall Study | Lost to Follow-up | 8 | 3 |
| Overall Study | SEMS Obstruction | 11 | 20 |
Baseline characteristics
| Characteristic | Uncovered Wallstent | Partially Covered Wallstent | Total |
|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 13 | 66 years STANDARD_DEVIATION 14 | 66 years STANDARD_DEVIATION 14 |
| Sex: Female, Male Female | 30 Participants | 38 Participants | 68 Participants |
| Sex: Female, Male Male | 31 Participants | 30 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 61 | 0 / 68 |
| serious Total, serious adverse events | 27 / 61 | 42 / 68 |
Outcome results
Primary
Time to Recurrent Biliary Obstruction
Biliary obstruction is the narrowing (stricture) of the bile duct. This narrowing prevents bile, which is formed in the liver, from being carried to the small bowel to digest fats. Symptoms of biliary obstruction are pain, jaundice (yellow skin and eyes), itchy skin and fever. Time to biliary obstruction is defined as the time from the placement of the stent to the time of biliary obstruction as reported by the participant via monthly interview questions or call to a pager if symptoms of recurrent biliary obstruction developed. Participants not experiencing recurrent biliary obstruction were censored at the date of last follow-up or date of death.
Time frame: Median follow-up of 125 days in the uncovered SEMS arm and 201 days in the partially covered SEMS arm
Population: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Uncovered Wallstent | Time to Recurrent Biliary Obstruction | 711 days |
| Partially Covered Wallstent | Time to Recurrent Biliary Obstruction | 357 days |
p-value: 0.53Log Rank
Secondary
Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism
Mechanisms of recurrent biliary obstructions are defined as tumor ingrowth, tumor overgrowth, stent migration, sludge, food debris, stent failed to expand and unknown. Stents may be obstructed by more than one mechanism, therefore, the total does not add up to the number of stent obstructions in each group.
Time frame: Median follow-up of 125 days in the uncovered SEMS arm and 201 days in the partially covered SEMS arm
Population: All randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Uncovered Wallstent | Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism | Food debris in the stent | 1 participants |
| Uncovered Wallstent | Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism | Tumor ingrowth | 8 participants |
| Uncovered Wallstent | Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism | Tumor overgrowth | 0 participants |
| Uncovered Wallstent | Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism | Stent migration | 0 participants |
| Uncovered Wallstent | Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism | Sludge | 1 participants |
| Uncovered Wallstent | Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism | Stent failed to expand | 0 participants |
| Uncovered Wallstent | Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism | Unknown | 2 participants |
| Partially Covered Wallstent | Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism | Stent failed to expand | 1 participants |
| Partially Covered Wallstent | Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism | Sludge | 4 participants |
| Partially Covered Wallstent | Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism | Tumor ingrowth | 6 participants |
| Partially Covered Wallstent | Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism | Food debris in the stent | 1 participants |
| Partially Covered Wallstent | Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism | Tumor overgrowth | 3 participants |
| Partially Covered Wallstent | Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism | Unknown | 2 participants |
| Partially Covered Wallstent | Number of Participants With Recurrent Biliary Obstruction Reported by Mechanism | Stent migration | 6 participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs)
Serious adverse events were defined as adverse events requiring an invasive procedure or hospitalization or resulting in death.
Time frame: From time of stent placement to participant death or lost to follow-up (up to 1302 days)
Population: All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Uncovered Wallstent | Number of Participants With Serious Adverse Events (SAEs) | 27 Participants |
| Partially Covered Wallstent | Number of Participants With Serious Adverse Events (SAEs) | 42 Participants |
Secondary
Patient Survival
Patient survival is defined as the date of the placement of the stent to the date of death. Participants lost to follow-up were analyzed in an intention-to-treat fashion and censored at the time of their last follow-up interview.
Time frame: Median follow-up of 125 days in the uncovered SEMS arm and 201 days in the partially covered SEMS arm
Population: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Uncovered Wallstent | Patient Survival | 239 days |
| Partially Covered Wallstent | Patient Survival | 227 days |
p-value: 0.997Log Rank