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

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.

Study Overview

• Status: Terminated
• Conditions: Cholangiocarcinoma; Hilar Lymphadenopathy; Biliary Stricture
• Intervention / Treatment: Procedure: PTBD; Procedure: ERC

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approach over ERC for Bismuth type 3 & 4 hilar strictures; 2) the generally quoted risks of PTBD are based on outdated studies and may be exaggerated; and 3) endoscopic diagnosis of indeterminate biliary strictures remains suboptimal despite the use of cholangioscopy and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

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 74085
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Sibley Memorial Hospital
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida - Jacksonville
    • Jacksonville, Florida, United States, 32258
      • Borland-Groover Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63103
      • Saint Louis University
    • Saint Louis, Missouri, United States, 63130
      • Washington University
  • New Hampshire
    • Lebanon, New Hampshire, United States, 02714
      • Dartmouth University
  • New York
    • Stony Brook, New York, United States, 11790
      • Stony Brook University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 49795
      • Vanderbilt University
  • Texas
    • Dallas, Texas, United States, 75203
      • Methodist Hospital Dallas
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College Of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: Boston University; Johns Hopkins University; Fox Chase Cancer Center; Washington University School of Medicine; Northwestern University; Yale University; University of Michigan; Emory University; Stony Brook University; University of Florida; University of Southern California; Medical College of Wisconsin; Vanderbilt University; Ohio State University; Cedars-Sinai Medical Center; University of Virginia; Virginia Commonwealth University; Case Western Reserve University; Methodist Health System; St. Louis University; Borland-Groover Clinic; Dartmouth University; Johns Hopkins Community Physicians
• Investigators: Principal Investigator: B. Joseph Elmunzer, Medical University of South Carolina

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2017
• Primary Completion (Actual): April 12, 2019
• Study Completion (Actual): April 12, 2019

Study Registration Dates

• First Submitted: May 26, 2017
• First Submitted That Met QC Criteria: May 30, 2017
• First Posted (Actual): June 1, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2020
• Last Update Submitted That Met QC Criteria: March 23, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Lymphadenopathy
• Other Study ID Numbers: Pro00063825

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No