Clinical trial NCT01829698: Efficacy and Safety Study of TUDCA Compare UDCA to Treatment Chronic Cholestatic Liver Disease-PBC
Official title: Evaluate the Efficacy And Safety Of TUDCA Compare UDCA In The Treatment Of Cholestatic Liver Disease-PBC by A Randomized,Double-Blind,Double Dummy,Parallel-Controlled,Multicenter Trial and The Consecutive Treatment By TUDCA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cholestatic Liver Disease
Keywords: tudca PBC Cholestasis tauroursodeoxycholic acid taurolite
Lead sponsor: Beijing Trendful Kangjian Medical Information Consulting Limited Company
Sponsor class: OTHER
First posted: 2013-04-11
Enrollment: 199
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Though ursodeoxycholate acid (UDCA) is the well known effective therapy for PBC,clinical effectiveness of UDCA may be limited by its poor absorption and extensive biotransformation.The more hydrophillic 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 ALP,total bilirubin, GGT,ALT and AST as secondary outcomes after patients were treated with TUDCA or UDCA for 24 weeks.

Detailed description: This is a double-blind, randomized, parallel controlled, multicenter, clinical trial. Subjects inclusion by randomization after passing the screening, continuous administration the test drug (Taurolite) or control drug (Ursofalk) treatment for 24 weeks. Compare the safety and efficacy of Taurolite vs Ursofalk.

At the end of the double-blind period，enroll 100 subjects from both two group randomly ,for a consecutive treatment use TUDCA up to 24 weeks. Further evaluate the efficacy and safety of tauroursodeoxycholic acid (TUDCA) in the treatment of adult primary biliary cirrhosis (PBC) for a long time up to one year. Also evaluate the regimen's efficacy and safety that udca take placed by TUDCA in the treatment of adult primary biliary cirrhosis (PBC) for the patients who use udca treatment for 24 weeks.

Eligibility criteria: Inclusion Criteria:

* 1 Ages Eligible for Study: 18 Years to 70 Years

  2 Alkaline phosphatase (ALP) ≥ 2 times the Upper Limits of Normal (ULN);

  3 Anti mitochondrial antibody (AMA) positive and / or anti-mitochondrial antibody subtype M2 (AMA-M2) positive; if the AMA and AMA-M2 were negative, need liver biopsy confirmed pathological changes in PBC.

Exclusion Criteria:

* 1．in the 3 months before screening received UDCA, hormones, immunosuppressive therapy;

  2．with extrahepatic biliary obstruction;

  3．accompanied by hepatitis B virus (HBV) and hepatitis C virus (HCV) infection;

  4．laboratory screening examination :
  1. hemoglobin (HB): male\< 11 g/dL, female \<10 g/dL \< g/dL;
  2. the total white blood cell (WBC) count \< 3000/mm3;
  3. the absolute neutrophil count (ANC) \<1500/mm3;
  4. platelet (PLT) count \<50000/mm3;
  5. serum albumin \<3.3g/dL;
  6. alanine aminotransferase (ALT) ≥ 10 ULN and / or aspartate aminotransferase (AST) ≥ 10ULN;
  7. ALT ≥ 5 ULN and / or AST ≥ 5 ULN with immunoglobulin G (IgG) ≥ 2ULN;
  8. total bilirubin (T-Bil) ≥ 4 ULN;
  9. prothrombin time (PT) prolonged ≥ 3 seconds (limit reference value based on) or PTA ≤ 60%;
  10. the serum creatinine (Cr) ≥ 1.5ULN.

  5．patients with esophageal variceal or bleeding, ascites, hepatic encephalopathy or other evidence of hepatic decompensation;

  6．diagnosed with liver cancer, suspected to have liver cancer, AFP \> 100ng/ml. As the AFP in 2 times the upper limit of normal to 100ng/ml, need re-check in 2 weeks, if their AFP \> 100ng/ml can not be included

  7．body mass index \>28 (Kg/m2);

  8．alcohol or drug abusers within the recent year;

  9．there is a serious heart, lung, kidney, digestive, nervous, mental disease, autoimmune diseases or malignant tumor

  10．drug-induced liver injury;

  11. plan to transplant or have had organ transplants;

  12． are unable or unwilling to provide informed consent or fails to comply with the test requirements;

  13．pregnant, lactating women.

Primary outcomes:
measure: Efficiency is defined as the patients composition whose ALP level of serum decreased more than 25% compared to baseline at treatment for 24 weeks.
timeFrame: 48 weeks
Secondary outcomes:
measure: The change of laboratory parameters about liver function
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Liver Research Center,Beijing Friendship Hospital
state: Beijing
Study officials:
affiliation: Beijing Friendship Hospital
name: Ji Dong Jia, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Ditan Hospital
name: Wen Xie, Doctor
role: STUDY_DIRECTOR
affiliation: Beijing YouAn Hospital
name: Hui Ping Yan, Doctor
role: STUDY_DIRECTOR
affiliation: Beijing 302 Hospital
name: Guo Feng Chen, Doctor
role: STUDY_DIRECTOR
affiliation: Peking University First Hospital
name: Gui Qiang Wang, Doctor
role: STUDY_DIRECTOR
affiliation: Peking University People's Hospital
name: Lai Wei, Doctor
role: STUDY_DIRECTOR
affiliation: Chinese PLA General Hospital
name: Liu Fang Cheng, Doctor
role: STUDY_DIRECTOR
affiliation: Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
name: Min De Zeng
role: STUDY_DIRECTOR
affiliation: RuiJin Hospital Affiliated To Shanghai Jiao Tong University School of Medicine
name: Qing Xie, Doctor
role: STUDY_DIRECTOR
affiliation: Affiliated HuaShan Hospital of Fudan University
name: Guang Feng Shi, Doctor
role: STUDY_DIRECTOR
affiliation: Affiliated Zhongshan Hospital of Fudan University
name: Ji Yao Wang, Doctor
role: STUDY_DIRECTOR
affiliation: Shanghai Changzheng Hospital
name: Xiao Hui Miao, Doctor
role: STUDY_DIRECTOR
affiliation: No.85 hospital of PLA
name: Cheng Wei Chen, Doctor
role: STUDY_DIRECTOR
affiliation: Shanghai Public Health Clinical Center
name: Shan Ming Wu, Doctor
role: STUDY_DIRECTOR
affiliation: Shanghai Eastern Hepatobiliary Surgery Hospital
name: He Ping Hu, Doctor
role: STUDY_DIRECTOR
affiliation: The First Affiliated Hospital,SunYat-Sen University
name: Min Hu Chen, Doctor
role: STUDY_DIRECTOR
affiliation: The Third Affiliated Hospital,SunYat-Sen University
name: Zhi Liang Gao, Doctor
role: STUDY_DIRECTOR
affiliation: Affiliated Southern Hospital of Southern Medical University
name: Jin Lin Hou, Doctor
role: STUDY_DIRECTOR
affiliation: The First Affiliated Hospital of Medical College,Zhejiang University
name: Ji Fang Sheng, Doctor
role: STUDY_DIRECTOR
affiliation: NO.6 People's Hospital of Hangzhou
name: Xiao Qing Fu, Doctor
role: STUDY_DIRECTOR
affiliation: Affiliated Huaxi Hospital of Sichuan University
name: Hong Tang, Doctor
role: STUDY_DIRECTOR
affiliation: The First Affiliated Hospital of the Fourth Military Medical University
name: Ying Han, Doctor
role: STUDY_DIRECTOR
affiliation: Affiliated TongJi Hospital Of Tongji Medical College Huazhong University Of Science&Technology
name: Qin Ning, Doctor
role: STUDY_DIRECTOR
affiliation: First Affiliated Hospital of Kunming Medical University
name: Li Ping Duan, Doctor
role: STUDY_DIRECTOR
affiliation: NO.3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
name: Jie Xu, Doctor
role: STUDY_DIRECTOR
References: