12-week Open-label, Phase IIIb Comparing Efficacy and Safety of Rosuvastatin (CRESTOR™) in Combination With Ezetimibe (GRAVITY)

A 12-week Open-label, Randomised, Parallel-group, Multicentre, Phase IIIb Study to Compare the Efficacy and Safety of Rosuvastatin (CRESTOR™) in Combination With Ezetimibe and Simvastatin in Patients With Hypercholesterolaemia and CHD

The purpose of this study is to determine whether treatment of Rosuvastatin (CRESTOR™) or Simvastatin given as monotherapy or given in combination with Ezetimibe, will lower the Low Density Lipoprotein Cholesterol (LDL-C) in patients with Hypercholesterolaemia and Coronary Heart Disease (CHD) or a CHD Risk Equivalent, Atherosclerosis or a 10-year CHD Risk of >20%

Study Overview

• Status: Completed
• Conditions: Atherosclerosis; Hypercholesterolemia; Coronary Heart Disease
• Intervention / Treatment: Drug: Rosuvastatin (Crestor); Drug: Ezetimibe; Drug: Simvastatin

• Study Type: Interventional
• Enrollment (Actual): 1743
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Research Site
• Brazil
  • SP
    • Sao Paulo, SP, Brazil
      • Research Site
• Chile
  • Santiago, Chile
    • Research Site
• Colombia
  • Brentwood, Colombia
    • Research Site
• Lithuania
  • Brentwood, Lithuania
    • Research Site
• Netherlands
  • Zwinderen, Netherlands
    • Research Site
• Peru
  • San Isidro Lima
    • Lima, San Isidro Lima, Peru
      • Research Site
• United States
  • Tennessee
    • Brentwood, Tennessee, United States
      • Research Site
• Venezuela
  • Brentwood, Venezuela
    • 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:

• Patients with with hypercholesterolaemia and CHD or a CHD risk equivalent, clinical evidence of atherosclerosis or a Framingham 10-year CHD risk score of >20
• Patients will need to sign an informed consent before any visit procedures can be performed, including procedures for the optional genetic research and biomarker studies.
• Patients must be 18 years or older and will be asked to stop taking any current cholesterol-lowering medications. Dietary counselling will be provided which will include an overview of the Therapeutic Lifestyle Change (TLC) diet the patients will be asked to follow

Exclusion Criteria:

• Use of lipid lowering drugs and other prohibited concomitant medications. History of statin-induced myopathy, or serious hypersensitivity reaction to other HMG-CoA reductase inhibitors (statins), including rosuvastatin, simvastatin and/or a history of hypersensitivity to any components of ezetimibe.
• Patients considered to be unstable by their physician after the following events:

a myocardial infarction, recent episode of unstable angina, myocardial revascularisation [percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft (CABG) surgery or another revascularisation procedure] or a transient ischaemic attack (TIA) or stroke and patients awaiting a planned myocardial revascularisation

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After 6 Weeks Combination Treatment	Percent change in LDL-C = (Combination treatment value - Baseline value)/Baseline value*100	Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) After 6 Weeks Combination Treatment	Percent change in HDL-C = (Combination treatment value - Baseline value)/Baseline value*100	Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
Percent Change in Total Cholesterol (TC) After 6 Weeks Combination Treatment	Percent change in TC = (Combination treatment value - Baseline value)/Baseline value*100	Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
Percent Change in Triglycerides (TG) After 6 Weeks Combination Treatment	Percent change in TG = (Combination treatment value - Baseline value)/Baseline value*100	Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
Percent Change in Non-high-density Lipoprotein Cholesterol (nonHDL-C) After 6 Weeks Combination Treatment	Percent change in nonHDL-C = (Combination treatment value - Baseline value)/Baseline value*100	Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
Percent Change in Apolipoprotein B (ApoB) After 6 Weeks Combination Treatment	Percent change in ApoB = (Combination treatment value - Baseline value)/Baseline value*100	Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
Percent Change in Apolipoprotein A1 (ApoA-1) After 6 Weeks Combination Treatment	Percent change in ApoA-1 = (Combination treatment value - Baseline value)/Baseline value*100	Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
Percent Change in TC/HDL-C After 6 Weeks Combination Treatment	Percent change in TC/HDL-C = (Combination treatment value - Baseline value)/Baseline value*100	Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
Percent Change in LDL-C/HDL-C After 6 Weeks Combination Treatment	Percent change in LDL-C/HDL-C = (Combination treatment value - Baseline value)/Baseline value*100	Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
Percent Change in Non-HDL-C/HDL-C After 6 Weeks Combination Treatment	Percent change in non-HDL-C/HDL-C = (Combination treatment value - Baseline value)/Baseline value*100	Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
Percent Change in ApoB/ApoA-1 After 6 Weeks Combination Treatment	Percent change in ApoB/ApoA-1 = (Combination treatment value - Baseline value)/Baseline value*100	Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
Percent Change in High-sensitivity C-reactive Protein (Hs-CRP) After 6 Weeks Combination Treatment	Percent change in hs-CRP = (Combination treatment value - Baseline value)/Baseline value*100	Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
Percent Change in LDL-C After 6 Weeks Monotherapy	Percent change in LDL-C = (Monotherapy treatment value - Baseline value)/Baseline value*100	Mean of Weeks 4 and 6 on monotherapy (Last observation carried forward)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Christie M Ballantyne, MD FACP FACC, Centre for Cardiovascular Disease Prevention; Study Chair: Margareta Grind, MD PhD FFPM, Medicine and Sciences AstraZeneca

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: September 5, 2007
• First Submitted That Met QC Criteria: September 5, 2007
• First Posted (Estimate): September 6, 2007

Study Record Updates

• Last Update Posted (Estimate): May 13, 2011
• Last Update Submitted That Met QC Criteria: May 11, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: Atherosclerosis; Coronary Heart Disease (CHD); Hypercholesterolaemia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Hypercholesterolemia; Atherosclerosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Simvastatin; Ezetimibe
• Other Study ID Numbers: D356FC00003