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

Hypercholesterolemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00844402
• Other study ID #: MT_PBC-2
• Status: Completed
• Phase: Phase 3
• First received: February 13, 2009
• Last updated: February 13, 2009
• Start date: January 2006
• Est. completion date: November 2007

Study information

• Verified date: February 2009
• Source: Medical University of Graz
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: November 2007
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypercholesterolemia
• Liver Cirrhosis
• Liver Cirrhosis, Biliary
• Primary Biliary Cirrhosis

Intervention

Drug:
• Atorvastatin
oral, 10 mg, daily, 48 weeks

Locations

Country	Name	City	State
Austria	Department of Internal Medicine, Medical University of Graz	Graz

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Graz

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Low-density lipoprotein cholesterol (LDL-C)		week 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes