A Trial of Percutaneous vs. Endoscopic Drainage of Suspected Klatskin Tumors (INTERCPT)

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

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

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.

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approach over ERC for Bismuth type 3 & 4 hilar strictures; 2) the generally quoted risks of PTBD are based on outdated studies and may be exaggerated; and 3) endoscopic diagnosis of indeterminate biliary strictures remains suboptimal despite the use of cholangioscopy and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

50% reduction in bilirubin level within 2 weeks of the study intervention without additional ERC or PTBD

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 related to PTBD and ERC, defined according to standard consensus guideline documents published in the interventional radiology and gastroenterology literature respectively.

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

Al-Kawas F, Aslanian H, Baillie J, Banovac F, Buscaglia JM, Buxbaum J, Chak A, Chong B, Cote GA, Draganov PV, Dua K, Durkalski V, Elmunzer BJ, Foster LD, Gardner TB, Geller BS, Jamidar P, Jamil LH, Keswani RN, Khashab MA, Lang GD, Law R, Lichtenstein D, Lo SK, McCarthy S, Melo S, Mullady D, Nieto J, Bayne Selby J, Singh VK, Spitzer RL, Strife B, Tarnaksy P, Taylor JR, Tokar J, Wang AY, Williams A, Willingham F, Yachimski P; In alphabetical order for the INTERCPT Study Group and the United States Cooperative for Outcomes Research in Endoscopy (USCORE). Percutaneous transhepatic vs. endoscopic retrograde biliary drainage for suspected malignant hilar obstruction: study protocol for a randomized controlled trial. Trials. 2018 Feb 14;19(1):108. doi: 10.1186/s13063-018-2473-2.