Phase III Randomized Study of Ursodiol With Vs Without Methotrexate for Primary Biliary Cirrhosis
methotrexate
+ ursodiol
Enfermedades del Conducto Biliar+9
+ Enfermedades del Tracto Biliar
+ Colestasis
Estudio de Tratamiento
Resumen
Fecha de inicio: 1 de enero de 1994
Fecha en la que se inscribió al primer participante.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.
Protocolo
Esta sección proporciona detalles del plan del estudio, incluyendo cómo está diseñado y qué se está evaluando.Se reclutarán 315 pacientes
Número total de participantes que el ensayo clínico espera reclutar.Estudio de Tratamiento
Elegibilidad
Los investigadores buscan pacientes que cumplan ciertos criterios, conocidos como criterios de elegibilidad: estado general de salud o tratamientos previos.Cualquier sexo
Sexo biológico de los participantes elegibles para inscribirse.De 20 a 69 años
Rango de edades de los participantes que pueden unirse al estudio.Voluntarios sanos no permitidos
Indica si personas sanas, sin la condición que se estudia, pueden participar.Condiciones
Patología
Criterios
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