Cholangiocarcinoma, Hilar Lymphadenopathy, Biliary Stricture
Conditions
Brief summary
The optimal approach to the drainage of malignant obstruction at the biliary hilum remains uncertain. This is a randomized comparative effectiveness study of percutaneous transhepatic biliary drainage (PTBD) vs. endoscopic retrograde cholangiography (ERC) as the first intervention in patients with cholestasis due to suspected malignant hilar obstruction.
Detailed description
Both percutaneous transhepatic biliary drainage (PTBD) and endoscopic retrograde cholangiography (ERC) are accepted approaches in the management of patients with malignant obstruction at the biliary hilum. In routine clinical practice, ERC is generally favored on the basis of: 1) high technical and clinical success rates for other (non-hilar) indications; 2) the perceived safety of ERC relative to PTBD; 3) the perceived ability to perform more comprehensive tissue sampling at the time of ERC compared to PTBD; 4) the avoidance of external tubes which are often needed for PTBD; and 5) because patients with suspected malignant hilar obstruction (MHO) typically present to and are managed by gastroenterologists. However: 1) observational data suggest that PTBD is superior for achieving complete drainage of MHO1 and some guidelines recommend the percutaneous approach over ERC for Bismuth type 3 & 4 hilar strictures; 2) the generally quoted risks of PTBD are based on outdated studies and may be exaggerated; and 3) endoscopic diagnosis of indeterminate biliary strictures remains suboptimal despite the use of cholangioscopy and multi-modal sampling. Although many patients who undergo initial ERC require subsequent PTBD for adequate drainage, no randomized trials comparing the two modalities for suspected MHO have been published. The main hypothesis is that even though PTBD will be more effective than ERC for decompression of suspected MHO, this advantage will be offset by the favorable safety profile and superior diagnostic capability of ERC. If, however, PTBD is found to be substantially superior (by a pre-specified margin) in terms of drainage, or if the potential advantages of ERC are not realized, then the existing clinical approach to MHO must be reappraised. Moreover, identifying patient and stricture characteristics that predict response to PTBD or ERC may be important for informing clinical decision-making and guidelines.
Interventions
Sponsors
Yale University
Virginia Commonwealth University
Vanderbilt University
Stony Brook University
University of Southern California
Case Western Reserve University
Medical College of Wisconsin
Dartmouth University
University of Florida
Northwestern University
Johns Hopkins University
Washington University School of Medicine
University of Michigan
Boston University
Ohio State University
Borland-Groover Clinic
Methodist Health System
St. Louis University
Fox Chase Cancer Center
Emory University
Cedars-Sinai Medical Center
Johns Hopkins Community Physicians
University of Virginia
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized comparative effectiveness trial
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥40 (to reduce the likelihood of enrolling patients with obstruction due to primary sclerosing cholangitis) 2. Cholestatic liver function tests, including serum alkaline phosphatase level ≥ 300 IU/L and bilirubin level ≥ 3.7 mg/dL 3. Radiographic evidence of a biliary hilar stricture OR intrahepatic but no extrahepatic biliary ductal dilation
Exclusion criteria
1. Known radiographic evidence of a Bismuth-Corlette type 1 biliary stricture 2. Known diagnosis of primary sclerosing cholangitis without suspicion of dominant hilar stricture 3. Recent gallbladder/biliary surgery within 12 months 4. Known Mirizzi syndrome 5. Known IgG4-mediated cholangiopathy 6. Significant liver metastatic disease interfering with safe/effective PTBD 7. Significant ascites interfering with safe/effective PTBD 8. Known regional malignant-appearing adenopathy or extra-biliary mass, indicating the need for concurrent EUS-FNA 9. Prior ERCP or PTBD for hilar obstruction 10. Surgically altered luminal anatomy other than prior Billroth reconstruction or Whipple resection 11. Standard general contraindications to ERCP or PTBD (e.g. hemodynamic instability, uncorrected coagulopathy, etc.) 12. Inability or unwillingness to follow study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Successful biliary drainage | 2 weeks | 50% reduction in bilirubin level within 2 weeks of the study intervention without additional ERC or PTBD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alternate definition of successful biliary drainage | 6 months | improvement in the serum bilirubin level to ≤2.5 mg/dL as a result of the index (randomization) intervention without the need for additional procedures. |
| Adverse events | 6 months | Adverse events related to PTBD and ERC, defined according to standard consensus guideline documents published in the interventional radiology and gastroenterology literature respectively. |
| Adequate tissue diagnosis | 6 months | A definitive diagnosis of malignancy documented in the subject's medical record. |
| Quality of life measure | 2-3 months after initial procedure | Promis Global Health Scale |
Countries
United States
Outcome results
None listed