Safety and Efficacy of Long-Term Treatment With Atorvastatin in Patients With Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) is frequently associated with hypercholesterolemia and possibly with an increased cardiovascular morbidity and mortality. Statins lower serum cholesterol levels and may thus improve the cardiovascular risk in PBC patients. The aim of our study therefore was to prospectively examine the efficacy of low-dose atorvastatin on indicators of cardiovascular risk such as dyslipidemia and vascular function as well as safety in patients with PBC.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia; Primary Biliary Cirrhosis
• Intervention / Treatment: Drug: Atorvastatin

Detailed Description

Primary biliary cirrhosis (PBC) is often associated with abnormalities in serum lipids. Hypercholesterolemia is an established risk factor for cardiovascular morbidity and mortality. Since many PBC patients have a very slow progression of their underlying liver disease cardiovascular risk factors may become more relevant as prognostic facors. Whether statins lower serum cholesterol levels and reduce the cardiovascular risk in PBC patients remains to be determined. Statins are generally well tolerated and are not associated with an increased risk of hepatotoxicity in patients with nonalcoholic fatty liver disease (NAFLD). However only limited data on safety on statins in chronic cholestatic liver diseases are available. In a recent pilot study at the Medical University of Graz atorvastatin did not statistically increase liver enzymes in PBC patients. However, data on long-term treatment with atorvastatin in these patients are not yet available. Moreover, long-term treatment with statins may have potential beneficial immunomodulatory effects on the disease course of PBC in analogy to other immune-mediated disorders such as rheumatoid arthritis and multiple sclerosis.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Department of Internal Medicine, Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• LDL-cholesterol > 130 mg/dl
• Primary biliary cirrhosis (AMA positive or biopsy proven)
• Male or female gender
• Age 18-70 years
• Normal kidney function

Exclusion Criteria:

• Primary biliary cirrhosis Stage III-IV (Ludwig Score)
• Liver cirrhosis
• Decompensated liver disease ( > Child-Pugh class B, ascites, esophageal varices)
• ALT or AST > 2x ULN
• Pregnancy or breastfeeding
• Premenopausal women without certain contraception
• Known hypersensitivity to HMG-CoA reductase inhibitors
• Current treatment with lipid-lowering agents other than atorvastatin; immunosuppressants, macrolides

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atorvastatin; Atorvastatin 10 mg per day for 48 weeks	Drug: Atorvastatin; oral, 10 mg, daily, 48 weeks; Other Names: Sortis10 mg, 1-21927, C10AA05

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Low-density lipoprotein cholesterol (LDL-C)	week 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60

Secondary Outcome Measures

Outcome Measure	Time Frame
Intima-media thickness of the common carotid artery (IMT), vascular wall stiffness (stiffness index SI), flow-mediated dilation of the brachial artery (FMD)	week 0, 48
Total cholesterol, triglycerides, VLDL-C, HDL-C, lipid profile, hs-CRP, AP, GGT, bilirubin, bile acids, immunoglobins	week 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60
AST, ALT, CK, PZ, AT, albumin, creatinine, blood cell count	week 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Investigators: Principal Investigator: Michael Trauner, M.D., Medical University of Graz, Department of Internal Medicine

Publications and helpful links

General Publications

• Stojakovic T, Claudel T, Putz-Bankuti C, Fauler G, Scharnagl H, Wagner M, Sourij H, Stauber RE, Winkler K, Marz W, Wascher TC, Trauner M. Low-dose atorvastatin improves dyslipidemia and vascular function in patients with primary biliary cirrhosis after one year of treatment. Atherosclerosis. 2010 Mar;209(1):178-83. doi: 10.1016/j.atherosclerosis.2009.08.052. Epub 2009 Sep 6.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: February 13, 2009
• First Submitted That Met QC Criteria: February 13, 2009
• First Posted (Estimate): February 16, 2009

Study Record Updates

• Last Update Posted (Estimate): February 16, 2009
• Last Update Submitted That Met QC Criteria: February 13, 2009
• Last Verified: February 1, 2009

More Information

Terms related to this study

• Keywords: Atherosclerosis; Statins; Vascular function; Cholestasis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Metabolic Diseases; Liver Diseases; Lipid Metabolism Disorders; Biliary Tract Diseases; Hyperlipidemias; Dyslipidemias; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Fibrosis; Liver Cirrhosis; Hypercholesterolemia; Liver Cirrhosis, Biliary; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: MT_PBC-2