Clinical trial NCT01857284: Safety and Efficacy of Tauroursodeoxycholic Acid Versus Ursofalk in the Treatment of Adult Primary Biliary Cirrhosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Biliary Cirrhosis
Keywords: Tauroursodeoxycholic Acid
Primary Biliary Cirrhosis
Safety
Efficacy
Lead sponsor: Beijing Friendship Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Trendful Kangjian Medical Information Consulting Limited Company
First posted: 2013-05-20
Enrollment: 216
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 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.


Eligibility criteria: 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

Primary outcomes:
measure: The proportion of patients who had AKP decline more than 25% after 24 weeks treatment of UDCA
timeFrame: 12 months
Secondary outcomes:
measure: ALP decline from baseline after 24 weeks treatment of TUDCA
timeFrame: 12 month
measure: Total bilirubin decline from baseline after 24 weeks treatment of TUDCA
timeFrame: 12 months
measure: GGT decline from baseline after 24 weeks treatment of TUDCA
timeFrame: 12 months
measure: ALT and AST decline from baseline after 24 weeks treatment of TUDCA
timeFrame: 12 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing 302 Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Ditan Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Youan Hospital
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Peiking University First Hosptial
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Guangzhou
country: China
facility: First Affiliated Hospital,SunYat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Third Affiliated Hospital,SunYat-Sen University
state: Guangdong
city: Wuhan
country: China
facility: Tongji Hospital
state: Hunan
city: Shanghai
country: China
facility: 85 Military Hospital
state: Shanghai
city: Shanghai
country: China
facility: Eastern Hepatobiliary Surgery Hospital
state: Shanghai
city: Shanghai
country: China
facility: Huashan Hospital
state: Shanghai
city: Shanghai
country: China
facility: NO.3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: RenJi Hospital
state: Shanghai
city: Shanghai
country: China
facility: RuiJin Hospital
state: Shanghai
city: Shanghai
country: China
facility: ShangHai Changzheng Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital
state: Shanghai
city: Xian
country: China
facility: Xijing Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital
state: Sichuan
city: Kunming
country: China
facility: First Affiliated Hospital Of KunMing Medical College
state: Yunnan
city: Hangzhou
country: China
facility: The Sixth People's Hospital of Hangzhou
state: Zhejiang
city: Zhejiang
country: China
facility: First Affiliated Hospital of Zhejiang University
state: Zhejiang
Study officials:
affiliation: Beijing Friendship Hospital
name: Dong Ji Jia, Doctor
role: PRINCIPAL_INVESTIGATOR
References: