Safety and Efficacy of Tauroursodeoxycholic Acid Versus Ursofalk in the Treatment of Adult Primary Biliary Cirrhosis

Capital Medical University

Status and phase: Completed; Phase 3

Conditions: Primary Biliary Cirrhosis

Treatments: Drug: Ursodeoxycholic Acid Capsules; Drug: Tauroursodeoxycholic Acid Capsules

Study type: Interventional

Funder types: Other

Identifiers

NCT01857284

2009L05707 (Other Grant/Funding Number)

Details and patient eligibility

About

Though ursodeoxycholate acid (UDCA) is the wellknown effective therapy for PBC, clinical effectiveness of UDCA may be limited by its poor absorption and extensive biotransformation. The more hydrophilic bile acid tauroursodeoxycholate (TUDCA) is the active ingredients of UDCA, and has been approved by state food and drug administration in China for treatment of cholesterol stones. So it is necessary to verify the efficacy and safety of TUDCA in the treatment of adult primary biliary cirrhosis. In this randomized, double-blinded, double-dummy, parallel-controlled and multicenter clinical trial, we detect the proportion of patients who had AKP decline more than 25% as the primary outcome; decline of AKP, total bilirubin, GGT, ALT and AST as secondary outcomes after patients were treated with TUDCA or UDCA for 24 weeks.

Enrollment: 216 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• written informed consent
• aged 18-70 years
• increase in alkaline phosphatase for 2 folds or more
• positive anti-mitochondrial antibody (AMA) with presence of antibodies against the pyruvate dehydrogenase complex (AMA-M2)；AMA-negative patients should be diagnosed as PBC with histologic evidence.

Exclusion criteria

1. patients who had been treated with UDCA, immunosuppressive medications within 3 months.
2. patients who had evidence of extrahepatic biliary obstruction
3. patients coinfection with HBV or HCV
4. patients with one of the followings: 1) hemoglobin(HB): <11 g/dl in male, <10 g/dl in female 2) white blood cell count <3000/mm3 3) neutrophile granulocyte <1500/mm3 4) platelet <50000/mm3; 5) serum albumin <3.3 g/dl 6) alanine aminotransferase(ALT)≥10×ULN and/or aspartate aminotransferase(ALT)≥10×ULN; 7) ALT≥5×ULN and/or AST≥5×ULN coexisting with immunoglobulin G (IgG) ≥2×ULN; 8) total bilirubin ≥4×ULN; 9) prothrombin time (PT) prolong 3 seconds or more, or PTA ≦60%; 10) creatinine ≥4×ULN.
5. patients with evidence of decompensated liver disease(ascites, gastrointestinal bleeding, hepatic encephalopathy et al.)
6. definitely diagnosed as hepatocellular carcinoma(HCC), probable HCC, AFP>100ng/ml.Patients with AFP>2×ULN while <100ng/ml should re-test 2 weeks later.
7. Body Mass Index >28 kg/m2
8. drug or alcohol abuse.
9. patient with severe disease of heart, lung, kidney, alimentary canal, neural system, autoimmune disease or tumor
10. patient had or on the scheduled of organ transplantation;
11. patient for whom the follow-up is considered impossible
12. pregnant or nursing woman

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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216 participants in 2 patient groups

Group 1

Experimental group

Description:

Tauroursodeoxycholic Acid Capsules,250mg,tid.

Treatment:

Drug: Tauroursodeoxycholic Acid Capsules

Group 2

Active Comparator group

Description:

Ursodeoxycholate acid capsules, 250mg,tid,

Treatment:

Drug: Ursodeoxycholic Acid Capsules