Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
University of Texas
Information provided by:
Office of Rare Diseases (ORD) Identifier:
First received: February 24, 2000
Last updated: June 23, 2005
Last verified: December 2001

February 24, 2000
June 23, 2005
January 1994
Not Provided
Not Provided
Not Provided
Complete list of historical versions of study NCT00004784 on Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
Phase III Randomized Study of Ursodiol With Vs Without Methotrexate for Primary Biliary Cirrhosis
Not Provided

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.

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.

Phase 3
Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Treatment
Liver Cirrhosis, Biliary
  • Drug: methotrexate
  • Drug: ursodiol
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Not Provided
Not Provided


--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

20 Years to 69 Years
Contact information is only displayed when the study is recruiting subjects
Not Provided
199/11873, UTSMC-29205400
Not Provided
Not Provided
National Center for Research Resources (NCRR)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • University of Texas
Study Chair: Burton Combes University of Texas
Office of Rare Diseases (ORD)
December 2001

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP