Trial of High-dose Urso in Primary Sclerosing Cholangitis

Multicentered Randomized Trial of High-dose Urso in Primary Sclerosing Cholangitis

This is a multicenter, randomized, controlled trial of high dose ursodiol versus placebo for patients with primary sclerosing cholangitis (PSC). The average duration of follow-up will be approximately five years with important clinical endpoints such as death, eligibility for liver transplantation, changes in histology and cholangiogram as well as liver biochemistries and quality of life data collected.

Study Overview

• Status: Terminated
• Conditions: Primary Sclerosing Cholangitis
• Intervention / Treatment: Drug: Placebo; Drug: Ursodeoxycholic Acid

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States
      • Mayo Clinic
  • Florida
    • Jacksonville, Florida, United States
      • Mayo Clinic
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States
      • St. Louis University
  • Nebraska
    • Omaha, Nebraska, United States
      • University of Nebraska Medical Center
  • Virginia
    • Richmond, Virginia, United States
      • Medical College of Virginia
  • Washington
    • Seattle, Washington, United States
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• Chronic cholestatic disease of at least six months' duration.
• Serum alkaline phosphatase at least 1 ½ times the upper limits of normal.
• Retrograde, operative, percutaneous, or magnetic resonance cholangiography demonstrating intrahepatic and/or extrahepatic biliary duct obstruction, beading, or narrowing consistent with PSC within one year of the study entry.
• Liver biopsy in the previous one year which is available for review and compatible with the diagnosis of PSC. Compatible biopsy features include fibrous cholangitis, ductopenia with periportal inflammation and biliary fibrosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo tablet that is identical (size, color, etc) to experimental ursodeoxycholic acid tablet.	Drug: Placebo; Placebo for Urso
Experimental: Ursodeoxycholic acid; Ursodeoxycholic acid 28-30 mg/kg/day	Drug: Ursodeoxycholic Acid; Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses; Other Names: UDCA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Failure	Treatment failure was defined as death, transplantation, meeting minimal listing criteria, development of varices, cholangiocarcinoma, or progression to cirrhosis	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Deaths	Death at any time up to 5 years	5 years
Number of Participants Who Have a Liver Transplantation	Liver transplantation at any time up to 5 years	5 years
Number of Participants Meeting Minimal Listing Criteria for Liver Transplantation	Meeting minimal listing criteria for liver transplantation at any time up to 5 years. Minimal listing criteria are defined as a MELD score of 14 or higher. The Model For End-Stage Liver Disease (MELD) is a numeric score with a range of 6 to 40, where a higher score means worse liver disease.	5 years
Number of Participants Who Developed Cholangiocarcinoma	Development of cholangiocarcinoma at any time up to 5 years	5 years
Number of Participants Who Developed Varices	Development of esophogeal and/or gastric varices	5 years
Number of Participants Who Developed Cirrhosis	Development of cirrhosis based on liver biopsy	5 years
Alkaline Phosphatase at 12 Months	Alkaline phosphatase divided by the upper limit of normal	12 months
Alkaline Phosphatase at 24 Months	Alkaline phosphatase divided by the upper limit of normal	24 months
Alkaline Phosphatase at 36 Months	Alkaline phosphatase divided by the upper limit of normal	36 months
Aspartate Aminotransferase at 12 Months	Aspartate aminotransferase at divided by the upper limit of normal	12 months
Aspartate Aminotransferase at 24 Months	Aspartate aminotransferase at divided by the upper limit of normal	24 months
Aspartate Aminotransferase at 36 Months	Aspartate aminotransferase at divided by the upper limit of normal	36 months
Bilirubin at 12 Months	Bilirubin divided by the upper limit of normal	12 months
Bilirubin at 24 Months	Bilirubin divided by the upper limit of normal	24 months
Bilirubin at 36 Months	Bilirubin divided by the upper limit of normal	36 months

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

General Publications

• Lindor KD, Kowdley KV, Luketic VA, Harrison ME, McCashland T, Befeler AS, Harnois D, Jorgensen R, Petz J, Keach J, Mooney J, Sargeant C, Braaten J, Bernard T, King D, Miceli E, Schmoll J, Hoskin T, Thapa P, Enders F. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009 Sep;50(3):808-14. doi: 10.1002/hep.23082.

Study record dates

Study Major Dates

• Study Start: July 1, 2002
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: April 21, 2003
• First Submitted That Met QC Criteria: April 21, 2003
• First Posted (Estimate): April 22, 2003

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 7, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: PSC; Urso
• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholangitis; Cholangitis, Sclerosing; Gastrointestinal Agents; Cholagogues and Choleretics; Ursodeoxycholic Acid
• Other Study ID Numbers: URSO (completed); R01DK056924 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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