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

A Randomized, Double-blinded, Double-dummy, Parallel-controlled and Multicenter Clinical Trial to Investigate Safety and Efficacy of Tauroursodeoxycholic Acid Capsules in Treatment of Adult Primary Biliary Cirrhosis

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.

Study Overview

• Status: Completed
• Conditions: Primary Biliary Cirrhosis
• Intervention / Treatment: Drug: Tauroursodeoxycholic Acid Capsules; Drug: Ursodeoxycholic Acid Capsules

• Study Type: Interventional
• Enrollment (Actual): 216
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Ditan Hospital
    • Beijing, Beijing, China
      • Beijing YouAn Hospital
    • Beijing, Beijing, China
      • Chinese PLA General Hospital
    • Beijing, Beijing, China
      • Peking University People's Hospital
    • Beijing, Beijing, China
      • Beijing 302 Hospital
    • Beijing, Beijing, China
      • Beijing Friendship Hospital
    • Beijing, Beijing, China
      • Peiking University First Hosptial
  • Guangdong
    • Guangzhou, Guangdong, China
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China
      • First Affiliated Hospital,SunYat-Sen University
    • Guangzhou, Guangdong, China
      • Third Affiliated Hospital,SunYat-Sen University
  • Hunan
    • Wuhan, Hunan, China
      • Tongji Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Changzheng Hospital
    • Shanghai, Shanghai, China
      • Shanghai Public Health Clinical Center
    • Shanghai, Shanghai, China
      • Shanghai Zhongshan Hospital
    • Shanghai, Shanghai, China
      • RenJi Hospital
    • Shanghai, Shanghai, China
      • 85 Military Hospital
    • Shanghai, Shanghai, China
      • Eastern Hepatobiliary Surgery Hospital
    • Shanghai, Shanghai, China
      • Huashan Hospital
    • Shanghai, Shanghai, China
      • NO.3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
    • Shanghai, Shanghai, China
      • Ruijin Hospital
  • Shanxi
    • Xian, Shanxi, China
      • Xijing Hospital
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital
  • Yunnan
    • Kunming, Yunnan, China
      • First Affiliated Hospital Of KunMing Medical College
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The Sixth People's Hospital of Hangzhou
    • Zhejiang, Zhejiang, China
      • First Affiliated Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Tauroursodeoxycholic Acid Capsules,250mg,tid.	Drug: Tauroursodeoxycholic Acid Capsules; 250mg.tid.po; Other Names: Taurolite
Active Comparator: Group 2; Ursodeoxycholate acid capsules, 250mg,tid,	Drug: Ursodeoxycholic Acid Capsules; 250mg.tid.po; Other Names: Ursofalk

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of patients who had AKP decline more than 25% after 24 weeks treatment of UDCA	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
ALP decline from baseline after 24 weeks treatment of TUDCA	12 month
Total bilirubin decline from baseline after 24 weeks treatment of TUDCA	12 months
GGT decline from baseline after 24 weeks treatment of TUDCA	12 months
ALT and AST decline from baseline after 24 weeks treatment of TUDCA	12 months

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Collaborators: Beijing Trendful Kangjian Medical Information Consulting Limited Company
• Investigators: Principal Investigator: Dong Ji Jia, Doctor, Beijing Friendship Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: May 16, 2013
• First Submitted That Met QC Criteria: May 16, 2013
• First Posted (Estimate): May 20, 2013

Study Record Updates

• Last Update Posted (Estimate): May 20, 2013
• Last Update Submitted That Met QC Criteria: May 16, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Primary Biliary Cirrhosis; Tauroursodeoxycholic Acid
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Fibrosis; Liver Cirrhosis; Liver Cirrhosis, Biliary; Anti-Infective Agents; Antiviral Agents; Gastrointestinal Agents; Cholagogues and Choleretics; Ursodeoxycholic Acid; Ursodoxicoltaurine
• Other Study ID Numbers: 2009L05707 (SFDA)