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

Phase 3

Completed

• Conditions: Primary Biliary Cirrhosis; Hypercholesterolemia
• Interventions: Drug: Atorvastatin

• Registration Number: NCT00844402
• Lead Sponsor: Medical University of Graz

Brief Summary

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.

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 Timeline

• Study Start: 2006-01
• Primary Completion: 2007-11
• Study Completion: 2007-11
• Status Verified: 2009-02
• Study First Submitted: 2009-02-13
• Study First Submitted QC: 2009-02-13
• Last Update Submitted: 2009-02-13
• Study First Posted: 2009-02-16
• Last Update Posted: 2009-02-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Atorvastatin	Atorvastatin	Atorvastatin 10 mg per day for 48 weeks

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Department of Internal Medicine, Medical University of Graz; 🇦🇹 Graz, Austria