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Fenofibrate in Combination With Ursodeoxycholic Acid in Primary Biliary Cirrhosis

Phase 3
Completed
Conditions
Primary Biliary Cirrhosis
Interventions
Registration Number
NCT02823353
Lead Sponsor
Xijing Hospital of Digestive Diseases
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
117
Inclusion Criteria
  1. Signed informed consent
  2. 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
  1. Pregnancy or desire of pregnancy.
  2. Breast-feeding.
  3. 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
  4. History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy, or poorly controlled ascites).
  5. History of urolithiasis, nephritis or renal failure (clearance of creatinine < 60 ml/mn).
  6. Hepatotoxic drugs use before recruiting.
  7. Fenofibrate anaphylaxis.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Fenofibrate + UDCAFenofibrateFenofibrate (200 mg/day) in combination with ursodeoxycholic acid (13-15 mg/kg/day)
Fenofibrate + UDCAUDCAFenofibrate (200 mg/day) in combination with ursodeoxycholic acid (13-15 mg/kg/day)
MonotherapyUDCAUDCA 13-15mg/kg/day
Primary Outcome Measures
NameTimeMethod
Rate of patients with complete biochemical responseWeek 48

Normalization of alkaline phosphatase (ALP) or decrease of ALP by more than 40% compared to the baseline.

Secondary Outcome Measures
NameTimeMethod
Change in liver biopsy examinations according to conventional Ludwig system.Week 48

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.

Change in liver stiffness status measured by magnetic resonance elastography.Week 48

The change of liver stiffness status at the end of the study compared to baseline checked by magnetic resonance elastography.

Change in serum levels of transaminase compared to the baseline.Weeks 0, 4, 8, 12, 24, and 48

Absolute change in serum levels of transaminase compared to the baseline.

Change in serum levels of bilirubin compared to the baseline.Weeks 0, 4, 8, 12, 24, and 48

Absolute change in serum levels of bilirubin compared to the baseline.

Change in serum levels of ALP compared to the baseline.Weeks 0, 4, 8, 12, 24, and 48

Absolute change in serum levels of ALP compared to the baseline.

GLOBE risk scores at week 48.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.

Trial Locations

Locations (1)

Xijing Hosipital

🇨🇳

Xi'an, Shaanxi, China

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