A Trial of Percutaneous vs. Endoscopic Drainage of Suspected Klatskin Tumors

Study Overview
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Brief Summary
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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
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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approach over ERC for Bismuth type 3 & 4 hilar strictures; 2) the generally quoted risks of PTBD are based on outdated studies and may be exaggerated; and 3) endoscopic diagnosis of indeterminate biliary strictures remains suboptimal despite the use of cholangioscopy and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.

Official Title
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A Multicenter Randomized Trial of Percutaneous Transhepatic Biliary Drainage vs. Endoscopic Retrograde Cholangiography for Decompression of Suspected Malignant Biliary Hilar Obstruction - the INTERCPT Trial

Conditions
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Cholangiocarcinoma, Hilar Lymphadenopathy, Biliary Stricture

Intervention / Treatment
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* Procedure: PTBD
* Procedure: ERC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥40 (to reduce the likelihood of enrolling patients with obstruction due to primary sclerosing cholangitis) Cholestatic liver function tests, including serum alkaline phosphatase level ≥ 300 IU/L and bilirubin level ≥ 3.7 mg/dL Radiographic evidence of a biliary hilar stricture OR intrahepatic but no extrahepatic biliary ductal dilation Exclusion Criteria: Known radiographic evidence of a Bismuth-Corlette type 1 biliary stricture Known diagnosis of primary sclerosing cholangitis without suspicion of dominant hilar stricture Recent gallbladder/biliary surgery within 12 months Known Mirizzi syndrome Known IgG4-mediated cholangiopathy Significant liver metastatic disease interfering with safe/effective PTBD Significant ascites interfering with safe/effective PTBD Known regional malignant-appearing adenopathy or extra-biliary mass, indicating the need for concurrent EUS-FNA Prior ERCP or PTBD for hilar obstruction Surgically altered luminal anatomy other than prior Billroth reconstruction or Whipple resection Standard general contraindications to ERCP or PTBD (e.g. hemodynamic instability, uncorrected coagulopathy, etc.) Inability or unwillingness to follow study protocol

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized comparative effectiveness trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Percutaneous Transhepatic Drainage<br>Subjects randomized to this arm will undergo PTBD as the first drainage intervention. | Procedure: PTBD<br>* Percutaneous access and tube placement into the bile duct<br>|
| Active Comparator: Endoscopic Retrograde Cholangiography<br>Subjects randomized to this arm will undergo ERC as the first drainage intervention. | Procedure: ERC<br>* Endoscopic access and stent placement in the bile duct<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful biliary drainage | 50% reduction in bilirubin level within 2 weeks of the study intervention without additional ERC or PTBD | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alternate definition of successful biliary drainage | 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. | 6 months | 
| Adverse events | Adverse events related to PTBD and ERC, defined according to standard consensus guideline documents published in the interventional radiology and gastroenterology literature respectively. | 6 months | 
| Adequate tissue diagnosis | A definitive diagnosis of malignancy documented in the subject's medical record. | 6 months | 
| Quality of life measure | Promis Global Health Scale | 2-3 months after initial procedure | 
| Quality of life measure | SF12 health survey | 2-3 months after initial procedure |