Fenofibrate in Combination With Ursodeoxycholic Acid in Primary Biliary Cirrhosis

Study Overview
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Brief Summary
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Ursodeoxycholic acid (UDCA) has been the only treatment for primary biliary cirrhosis (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. Both lab research and some clinical studies suggest that fenofibrate could improve cholestasis in multiple ways including reduce of bile acid synthesis, increase of biliary secretion and anti-inflammation effect. Here we start a random, open and parallel clinical research to explore the effect of fenofibrate in the PBC treatment.

Official Title
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Fenofibrate in Combination With Ursodeoxycholic Acid in Primary Biliary Cirrhosis: a Randomized Control Study

Conditions
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Primary Biliary Cirrhosis

Intervention / Treatment
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* Drug: Fenofibrate
* 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/ALT > 1N) activities; c.Histological hepatic injuries consistent with PBC. 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. Fenofibrate 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: Fenofibrate + UDCA<br>Fenofibrate (200 mg/day) in combination with ursodeoxycholic acid (13-15 mg/kg/day) | Drug: Fenofibrate<br>* Fenofibrate 200mg/day<br>Drug: UDCA<br>* UDCA 13-15mg/kg/day<br>|
| Active Comparator: Monotherapy<br>UDCA 13-15mg/kg/day | Drug: UDCA<br>* UDCA 13-15mg/kg/day<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 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in liver biopsy examinations according to conventional Ludwig system. | Histological evolution will be checked by liver biopsy at the end of the study to compare with baseline histological status. The Ludwig histological classification schemes will be used, which categorised the disease into four stages. | Week 48 | 
| GLOBE risk scores at week 48. | The prognostic scores will be calculated at end of the study by GLOBE scoring system (proposed by Global PBC Study Group), which calculated based on serum values of bilirubin, ALP, albumin and platelet count after 1 year of UDCA therapy and age at baseline. | 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 levels of ALP compared to the baseline. | Absolute change in serum levels of ALP compared to the baseline. | Weeks 0, 4, 8, 12, 24, and 48 | 
| Change in serum levels of bilirubin compared to the baseline. | Absolute change in serum levels of bilirubin compared to the baseline. | Weeks 0, 4, 8, 12, 24, and 48 | 
| Change in serum levels of transaminase compared to the baseline. | Absolute change in serum levels of transaminase 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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PBC, UDCA, Fenofibrate