Rosuvastatin for Hepatitis C

Treatment With Rosuvastatin in Patients With Hepatitis C

Objective: Determine if maximum doses of rosuvastatin are safe in patients infected with hepatitis C and if the so called pleiotropic effects of rosuvastatin cause a decrease in the HCV viral load.

Primary study parameters: 1. to which extend causes rosuvastatin serious side effects like rhabdomyolysis and hepatotoxicity in patients chronically infected with hepatitis C? 2. does treatment with rosuvastatin in HCV infected patients lead to lower HCV-RNA viral load? 3. Is a decrease in LDL correlated to a decrease in HCV-RNA load?

Study Overview

• Status: Withdrawn
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: rosuvastatin

Detailed Description

Study design: it's a pilot study in which the patients form their own control group. A total of 10 patients will be included. To evaluate the effect of maximum doses of rosuvastatin on liver function and side effects, first 2 patients will be treated and evaluated. If they experience no serious adverse events then a further 8 patients will be included. The dose of rosuvastatin will be increased over a period of 4 weeks.

Intervention: based on experience in treating dyslipidemia, gradually increasing the dose of rosuvastatin diminishes the experienced side effects and decreases the chances of developing hepatotoxicity. Therefore in this study we chose to increase the dose (see flowchart). Patients will start with 5 mg a day wich will be increased after 1 week to 10 mg per day. After the second week of therapy a further increase to 20 mg per day is executed. This dose will be given for another 2 weeks. At week 4 of treatment a further increase to 40 mg is done.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age between 18 and 65 years
• All patients with hepatitis C (all genotypes)
• negative for hepatitis B and HIV
• ALAT < 2,5 x below the upper limit of normal
• serological evidence of hepatitis C infection with detectable HCV-RNA (with Bayer Versant HCV bDNA V3.0)
• failed current standard of care treatment with peginterferon and ribavirin
• WHO-score ≤1
• fertile women must have a negative pregnancy test in the week before start of medication. Use of contraceptives during the whole study-period
• physically and mentally able to attend outpatients clinics

Exclusion Criteria:

• Hepatitis C patiënts naive for (peg)interferon and ribavirin treatment
• Alcohol abuses (> 20 grams per day) in the last year
• liver cirrhosis detected through liver biopsy or decompensated liver disease (child-pugh B or C)
• concomitant treatment with hepatotoxic medication / interfering with CYP450 system: anti-fungal medication (voriconazole), antibiotics (gentamycine, azitromycine, claritromycin, erytromycin), immuun-suppresive drugs (cyclosporine), anti-arythmia (diltiazem, verapamil) and tuberculostatic drugs (rifampicin).
• current statin use
• active pregnancy or wish of pregnangy
• use of grapefruit juice
• mentally not fit to participate in the study
• daily use of more than 2 grams of paracetamol

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
occurrence of serious side effects like rhabdomyolysis and hepatotoxicity during treatment
decrease of HCV-RNA viral load during treatment
decrease of LDL during treatment

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Investigators: Principal Investigator: I.M. Hoepelman, Professor, UMC Utrecht; Principal Investigator: H. Lokhorst, MD PhD, UMC Utrecht

Publications and helpful links

General Publications

• Kapadia SB, Chisari FV. Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2561-6. doi: 10.1073/pnas.0409834102. Epub 2005 Feb 7.
• Ye J, Wang C, Sumpter R Jr, Brown MS, Goldstein JL, Gale M Jr. Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15865-70. doi: 10.1073/pnas.2237238100. Epub 2003 Dec 10.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): October 1, 2007
• Study Completion (Anticipated): October 1, 2007

Study Registration Dates

• First Submitted: September 1, 2006
• First Submitted That Met QC Criteria: September 1, 2006
• First Posted (Estimate): September 4, 2006

Study Record Updates

• Last Update Posted (Estimate): June 3, 2015
• Last Update Submitted That Met QC Criteria: June 2, 2015
• Last Verified: February 1, 2009

More Information

Terms related to this study

• Keywords: hepatitis C; rosuvastatin; geranylgeranylation; HCV-RNA load
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: 06-125

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No