RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases (RACING Trial)

The clinical efficacy of LDL-lowering therapy have been proven with strong evidences and more emphasized. However, there are also growing concerns that high-intensity statin would be related to increased risk of adverse effects. In addition, there was an inconsistency of efficacy of statin according to ethnic population. Asian population showed more profound LDL reduction not only from high potent statin but from moderate to low potent statin. Conventional strategies for lowering LDL-cholesterol was focused on statins, therefore doubling of previously described dose of statin would be common way in patients with inadequate lowering LDL-cholesterol level. Additive ezetimibe will also an alternative strategy not only to lower LDL-cholesterol level and also to reduce the need of dosage of high-intensity statin to fulfill sufficient LDL-cholesterol lowering effect. We will evaluate whether additive ezetimibe with rosuvastatin will have comparable clinical efficacy in terms of clinical outcomes and goal attainment of LDL-C compared to rosuvastatin monotherapy.

Study Overview

• Status: Unknown
• Conditions: Cardiovascular Diseases; Cerebrovascular Disease; Peripheral Atherosclerotic Disease
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Rosuvastatin plus ezetimibe

• Study Type: Interventional
• Enrollment (Anticipated): 3780
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine
    • Contact: Yang-Soo Jang, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 19-80 years
• Documented CVD (cardiovascular disease), previous MI(Myocardial Infarction), ACS (Acute Coronary Syndrome), coronary revascularization and other arterial revascularization procedures, ischemic stroke, or PAD (peripheral artery disease)

Exclusion Criteria:

• Active liver disease or persistent unexplained serum AST or ALT elevation more than 2 times the upper limit of normal range
• Allergy or hypersensitivity to any statin or ezetimibe
• Solid organ transplantation recipient
• History of any adverse drug reaction requiring discontinuation of statin
• Pregnant women, women with potential childbearing, or lactating women
• Life expectancy less than 3 years
• Inability to follow the patient over the period of 1 year after enrollment, as assessed by the investigator
• Inability to understand or read the informed content

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High-intensity statin monotherapy; Statin monotherapy	Drug: Rosuvastatin; Subjects will start rosuvastatin 20 mg a day irrespective of previous lipid-lowering treatment or LDL-cholesterol level as current US guideline.
Experimental: Statin plus ezetimibe combination therapy	Drug: Rosuvastatin plus ezetimibe; Subjects will start single combination pill of rosuvastatin 10 mg plus ezetimibe 10 mg a day irrespective of previous lipid-lowering treatment or LDL-cholesterol level.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of cardiovascular death	Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.)	Clinical status including medication and clinical events will be evaluated at 2 months.
Composite of cardiovascular death	Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.)	Clinical status including medication and clinical events will be evaluated at 6 months.
Composite of cardiovascular death	Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.)	Clinical status including medication and clinical events will be evaluated at every years until 3 years.
Major cardiovascular event	Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.)	Clinical status including medication and clinical events will be evaluated at 2 months.
Major cardiovascular event	Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.)	Clinical status including medication and clinical events will be evaluated at 6 months.
Major cardiovascular event	Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.)	Clinical status including medication and clinical events will be evaluated at every years until 3 years.
Composite of nonfatal stroke	Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.)	Clinical status including medication and clinical events will be evaluated at 2 months.
Composite of nonfatal stroke	Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.)	Clinical status including medication and clinical events will be evaluated at 6 months.
Composite of nonfatal stroke	Composite of cardiovascular death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.)	Clinical status including medication and clinical events will be evaluated at every years until 3 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical efficacy of lipid lowering treatment	The proportion of participants whose LDL cholesterol is lower than 70mg/dL (1,2,3 years after enrollment); Composite of all death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.); Statin discontinuation or dose-reduction caused by intolerance; new-onset DM, muscle-related adverse events, gastrointestinal symptom, gallbladder-related event, major bleeding, cancer, new-onset neurocognitive disorder, cataract surgery	3years
Clinical safety of lipid lowering treatment	The proportion of participants whose LDL cholesterol is lower than 70mg/dL (1,2,3 years after enrollment); Composite of all death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.); Statin discontinuation or dose-reduction caused by intolerance; new-onset DM, muscle-related adverse events, gastrointestinal symptom, gallbladder-related event, major bleeding, cancer, new-onset neurocognitive disorder, cataract surgery	3years
statin discontinuation and intolerance	The proportion of participants whose LDL cholesterol is lower than 70mg/dL (1,2,3 years after enrollment); Composite of all death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.); Statin discontinuation or dose-reduction caused by intolerance; new-onset DM, muscle-related adverse events, gastrointestinal symptom, gallbladder-related event, major bleeding, cancer, new-onset neurocognitive disorder, cataract surgery	3years
Clinical adverse events	The proportion of participants whose LDL cholesterol is lower than 70mg/dL (1,2,3 years after enrollment); Composite of all death, major cardiovascular event, nonfatal stroke (Major cardiovascular event include any coronary or peripheral revascularization and hospitalization for any cardiovascular events including ischemic heart disease, heart failure, peripheral arterial disease.); Statin discontinuation or dose-reduction caused by intolerance; new-onset DM, muscle-related adverse events, gastrointestinal symptom, gallbladder-related event, major bleeding, cancer, new-onset neurocognitive disorder, cataract surgery	3years

Collaborators and Investigators

• Sponsor: Yonsei University

Publications and helpful links

General Publications

• Kim BK, Hong SJ, Lee YJ, Hong SJ, Yun KH, Hong BK, Heo JH, Rha SW, Cho YH, Lee SJ, Ahn CM, Kim JS, Ko YG, Choi D, Jang Y, Hong MK; RACING investigators. Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial. Lancet. 2022 Jul 30;400(10349):380-390. doi: 10.1016/S0140-6736(22)00916-3. Epub 2022 Jul 18.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2017
• Primary Completion (Anticipated): January 15, 2022
• Study Completion (Anticipated): February 15, 2023

Study Registration Dates

• First Submitted: February 1, 2017
• First Submitted That Met QC Criteria: February 2, 2017
• First Posted (Estimate): February 7, 2017

Study Record Updates

• Last Update Posted (Actual): January 16, 2019
• Last Update Submitted That Met QC Criteria: January 10, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cardiovascular Diseases; Cerebrovascular Disorders; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Ezetimibe
• Other Study ID Numbers: 4-2016-1025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No