Rosuvastatin Impact on Ventricular Remodelling Lipids and Cytokines

A Double-blind, Randomised, Placebo-controlled, Parallel-group, Multicentre, Phase III Study to Assess the Impact of Rosuvastatin Treatment for 26 Weeks (Titrated to a Maximum Dose of 40mg Once Daily) on Left Ventricular Function, Cytokines and Lipid Parameters in Patients With Established Systolic Chronic Heart Failure.

The purpose of this study is to assess the effect of rosuvastatin (up-titrated to a dose of 40mg/day) compared to placebo on cardiac remodelling, estimated by change in left ventricular ejection fraction on radionuclide ventriculography, at 26 weeks post randomisation from baseline.

Study Overview

• Status: Completed
• Conditions: Heart Failure, Congestive
• Intervention / Treatment: Drug: Rosuvastatin

• Study Type: Interventional
• Enrollment: 160
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia
      • Research Site
  • New South Wales
    • Gosford, New South Wales, Australia
      • Research Site
    • Newcastle, New South Wales, Australia
      • Research Site
    • Sydney, New South Wales, Australia
      • Research Site
    • Wollongong, New South Wales, Australia
      • Research Site
  • Queensland
    • Brisbane, Queensland, Australia
      • Research Site
    • Nambour, Queensland, Australia
      • Research Site
  • South Australia
    • Adelaide, South Australia, Australia
      • Research Site
  • Tasmania
    • Launceston, Tasmania, Australia
      • Research Site
  • Victoria
    • Geelong, Victoria, Australia
      • Research Site
    • Melbourne, Victoria, Australia
      • Research Site
    • Mildura, Victoria, Australia
      • Research Site
  • Western Australia
    • Perth, Western Australia, Australia
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Signed informed consent, males or females aged 18 or older, LVEF ≤ 40% assessed by RNVG or contrast ventriculogram or ≤ 35% assessed by TTE within the previous 6 months, LVEF < 45% as assessed by RNVG during Visit 1, NYHA Class II, III or IV symptoms primarily related to heart failure, ischaemic and non-ischaemic patients and on stable heart failure therapy as defined by physician's best practice.

Exclusion Criteria:

• Key exclusion criteria include acute myocarditis within the last 12 months, diabetes mellitus not controlled by diet, oral therapy or insulin therapy, homozygous familial hypercholesterolaemia, receiving biventricular pacing or expected to receive biventricular pacing in the next 6 months, subjects who normally would be considered for statin therapy in the next 6 months, sever hypertension, history of definite myocardial infarction, cerebrovascular accident, percutaneous transluminal coronary angioplasty or coronary bypass graft within 3 months prior to enrolment in the study, body mass index < 15, plus others.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Determine the effect of rosuvastatin (up-titrated to a dose of 40mg/day) compared to placebo on cardiac remodelling, estimated by change in left ventricular ejection fraction on radionuclide ventriculography, at 26 weeks post randomization from baseline.

Secondary Outcome Measures

Outcome Measure
Determine the effects of rosuvastatin (up-titrated to a dose of 40mg/day) compared to placebo by measuring:
Changes from baseline at 26 weeks post-randomisation, of left ventricular (LV) end-diastolic and end-systolic diameter, and LV fraction shortening, as determined by transthoracic echocardiography.
The percentage change in lipid parameters: total cholesterol, low density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides after 6, 12 and 26 weeks post-randomisation
Changes from baseline at 26 weeks post-randomisation in neurohormonal and immunological markers: norepinephrine, endothelin, N-terminal pro-brain natriuretic peptide, high-sensitivity C-reactive protein, tumour necrosis factor α and interleukin 6.
Assess the safety of rosuvastatin over 26 weeks determined by the incidence and severity of adverse events and abnormal laboratory values.
Assess change in quality of life score, as determined by the Minnesota Living with Heart Failure questionnaire.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Henry Krum, MBBS PhD FRACP, Clinical Pharmacology, Department of Epidemiology and Preventative Medicine, Monash University, Alfred Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2003

Study Registration Dates

• First Submitted: October 16, 2005
• First Submitted That Met QC Criteria: October 16, 2005
• First Posted (Estimate): October 18, 2005

Study Record Updates

• Last Update Posted (Estimate): November 19, 2010
• Last Update Submitted That Met QC Criteria: November 18, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: Ischaemic or non-ischaemic systolic congestive heart failure
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; 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: 4522AS/0002