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Phase III Randomized Study of Ursodiol With Vs Without Methotrexate for Primary Biliary Cirrhosis

Primary Purpose

Liver Cirrhosis, Biliary

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
methotrexate
ursodiol
Sponsored by
National Center for Research Resources (NCRR)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cirrhosis, Biliary focused on measuring cirrhosis, gastrointestinal disorders, primary biliary cirrhosis, rare disease

Eligibility Criteria

20 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- The following criteria must be met prior to study entry and ursodiol treatment: Bilirubin less than 3 mg/dL Alkaline phosphatase at least 1.5 times normal limits Albumin at least 3 g/dL The following criteria must be met prior to randomization to Arms I and II: Primary biliary cirrhosis (PBC), i.e.: Cholestatic liver disease for at least 6 months prior to randomization Liver biopsy compatible with PBC within 6 months prior to randomization No biliary obstruction on ultrasound, computerized tomography, or cholangiography The following exclude: Asymptomatic and stage I liver histology (Ludwig classification) Hepatic encephalopathy Ascites Variceal bleeding No liver disease of other etiology, e.g.: Chronic hepatitis B or C Autoimmune chronic active hepatitis Alcoholic liver disease Sclerosing cholangitis Drug-induced liver disease Symptomatic or obstructive gallstones --Prior/Concurrent Therapy-- At least 6 months since the following immunosuppressives: Cyclosporine Tacrolimus Methotrexate At least 3 months since other immunosuppressives, e.g.: Azathioprine Chlorambucil Colchicine Corticosteroids Penicillamine At least 3 months since rifampin --Patient Characteristics-- Life expectancy: No major illness limiting life span Hematopoietic: WBC at least 2500/mm3 Absolute granulocyte count at least 1500/mm3 Platelet count at least 80,000/mm3 Hepatic: See Disease Characteristics Renal: Creatinine clearance at least 60 mL/min Pulmonary: No diffusion capacity or vital capacity less than 50% of predicted Other: Antimitochondrial antibody positive HIV antibody negative No alcoholism within the past 2 years No epilepsy requiring phenytoin No malignancy within the past 5 years other than skin cancer No pregnant women Adequate contraception required of fertile patients

Sites / Locations

    Outcomes

    Primary Outcome Measures

    Secondary Outcome Measures

    Full Information

    First Posted
    February 24, 2000
    Last Updated
    June 23, 2005
    Sponsor
    National Center for Research Resources (NCRR)
    Collaborators
    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Texas
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00004784
    Brief Title
    Phase III Randomized Study of Ursodiol With Vs Without Methotrexate for Primary Biliary Cirrhosis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2001
    Overall Recruitment Status
    Completed
    Study Start Date
    January 1994 (undefined)
    Primary Completion Date
    undefined (undefined)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Name of the Sponsor
    National Center for Research Resources (NCRR)
    Collaborators
    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Texas

    4. Oversight

    5. Study Description

    Brief Summary
    OBJECTIVES: I. Compare the effects of ursodiol (ursodeoxycholic acid), with and without methotrexate, on pruritus, incapacitation index, and serum markers of activity and severity in patients with primary biliary cirrhosis. II. Compare the effects of these regimens on the development of ascites, encephalopathy, varices (or bleeding from pre-existing varices), histologic liver changes, transplantation, and survival. III. Compare the toxicity and safety of each regimen.
    Detailed Description
    PROTOCOL OUTLINE: This is a randomized, double-blind study. Patients are stratified by participating institution and Ludwig histologic stage. All patients are treated with ursodiol (ursodeoxycholic acid, UDCA) for 6 months. If entry criteria continue to be met, patients are randomly assigned to UDCA/methotrexate or UDCA/placebo. Combination therapy continues for at least 5 years.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Liver Cirrhosis, Biliary
    Keywords
    cirrhosis, gastrointestinal disorders, primary biliary cirrhosis, rare disease

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Masking
    Double
    Allocation
    Randomized
    Enrollment
    315 (false)

    8. Arms, Groups, and Interventions

    Intervention Type
    Drug
    Intervention Name(s)
    methotrexate
    Intervention Type
    Drug
    Intervention Name(s)
    ursodiol

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    20 Years
    Maximum Age & Unit of Time
    69 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- The following criteria must be met prior to study entry and ursodiol treatment: Bilirubin less than 3 mg/dL Alkaline phosphatase at least 1.5 times normal limits Albumin at least 3 g/dL The following criteria must be met prior to randomization to Arms I and II: Primary biliary cirrhosis (PBC), i.e.: Cholestatic liver disease for at least 6 months prior to randomization Liver biopsy compatible with PBC within 6 months prior to randomization No biliary obstruction on ultrasound, computerized tomography, or cholangiography The following exclude: Asymptomatic and stage I liver histology (Ludwig classification) Hepatic encephalopathy Ascites Variceal bleeding No liver disease of other etiology, e.g.: Chronic hepatitis B or C Autoimmune chronic active hepatitis Alcoholic liver disease Sclerosing cholangitis Drug-induced liver disease Symptomatic or obstructive gallstones --Prior/Concurrent Therapy-- At least 6 months since the following immunosuppressives: Cyclosporine Tacrolimus Methotrexate At least 3 months since other immunosuppressives, e.g.: Azathioprine Chlorambucil Colchicine Corticosteroids Penicillamine At least 3 months since rifampin --Patient Characteristics-- Life expectancy: No major illness limiting life span Hematopoietic: WBC at least 2500/mm3 Absolute granulocyte count at least 1500/mm3 Platelet count at least 80,000/mm3 Hepatic: See Disease Characteristics Renal: Creatinine clearance at least 60 mL/min Pulmonary: No diffusion capacity or vital capacity less than 50% of predicted Other: Antimitochondrial antibody positive HIV antibody negative No alcoholism within the past 2 years No epilepsy requiring phenytoin No malignancy within the past 5 years other than skin cancer No pregnant women Adequate contraception required of fertile patients
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Burton Combes
    Organizational Affiliation
    University of Texas
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Learn more about this trial

    Phase III Randomized Study of Ursodiol With Vs Without Methotrexate for Primary Biliary Cirrhosis

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