Trial of High-dose Urso in Primary Sclerosing Cholangitis

Study Overview
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Brief Summary
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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.

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

Conditions
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Primary Sclerosing Cholangitis

Intervention / Treatment
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* Drug: Ursodeoxycholic Acid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urso, PSC