Fuzhenghuayu for Patients With PBC Who Had An Inadequate Response to Ursodeoxycholic Acid

Study Overview
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Brief Summary
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Ursodeoxycholic acid (UDCA) has been the only treatment for PBC approved by US and European drug administrations. Long-term use of UDCA(13-15 mg/kg/day) in patients with PBC improves serum liver biochemistries and survival free of liver transplantation However, about 40% of patients do not respond to UDCA optimally as assessed by known criteria for biochemical response. Those patients represent the group in need for additional therapies, having increased risk of disease progression and decreased survival free of liver transplantation. And UDCA has less effect on PBC patients whose pathology stage 3-4. Liver fibrosis might jeopardize the UDCA effect. Fuzhenghuayu is a Chinese traditional medicine for liver fibrosis and cirrhosis. Both lab research and some clinical studies suggest that Fuzhenghuayu could significantly reverse liver fibrosis and cirrhosis due to different kind of etiology. Here we start a random, open and parallel clinical research to explore the effect of Fuzhenghuayu combined with UDCA in the PBC treatment.

Conditions
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Primary Biliary Cirrhosis

Intervention / Treatment
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* Drug: Fuzhenghuayu
* Drug: UDCA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Patient with PBC defined by 2 in 3 of the following criteria: a.Positive antimitochondrial antibody type M2; b.Abnormal serum alkaline phosphatases (ALP > 1,5N) and aminotransferase (AST or ALT > 1N) activities; c.Histological hepatic injuries consistent with PBC. Had been treated with UDCA more than 6 months, and failed to achieve a complete biochemical response. Exclusion Criteria: Pregnancy or desire of pregnancy. Breast-feeding. Co-existing liver diseases such as acute or chronic viral hepatitis, alcoholic liver disease, choledocholithiasis, autoimmune hepatitis, biopsy-proven non-alcoholic fatty liver disease, Wilson's disease and hemochromatosis. History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy, or poorly controlled ascites). History of urolithiasis, nephritis or renal failure (clearance of creatinine < 60 ml/mn). Hepatotoxic drugs use before recruiting. Fuzhenghuayu anaphylaxis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fuzhenghuayu+UDCA<br>Regular UDCA treatment combination with Fuzhenghuayu | Drug: Fuzhenghuayu<br> <br> Drug: UDCA<br> <br> |
| Active Comparator: Monotherapy<br>UDCA monotherapy | Drug: UDCA<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients with complete biochemical response | Normalization of alkaline phosphatase (ALP) or decrease of ALP by more than 40% compared to the baseline. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in liver biopsy examinations compared to the baseline. | Histological evolution will be checked by liver biopsy at the end of the study to compare with baseline histological status. | Week 48 | 
| Change in GLOBE scores after treatment. | The prognostic scores will be calculated at entry and end of study by GLOBE scoring system. | Week 48 | 
| Change in liver stiffness status measured by magnetic resonance elastography | The change of liver stiffness status at the end of the study compared to baseline checked by magnetic resonance elastography. | Week 48 | 
| Change in serum alkaline phosphatase (ALP) level | Change in serum levels of ALP (IU/L) compared to the baseline. | Weeks 0, 4, 8, 12, 24, and 48 | 
| Change in serum bilirubin level | Change in serum levels of bilirubin (mg/dL) compared to the baseline | Weeks 0, 4, 8, 12, 24, and 48 | 
| Change in serum transaminase level | Change in serum levels of transaminase (IU/L) compared to the baseline | Weeks 0, 4, 8, 12, 24, and 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fuzhenghuayu