NCT03044665

Brief Summary

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
3,780

participants targeted

Target at P75+ for not_applicable cardiovascular-diseases

Timeline
Completed

Started Mar 2017

Longer than P75 for not_applicable cardiovascular-diseases

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 1, 2017

Completed
6 days until next milestone

First Posted

Study publicly available on registry

February 7, 2017

Completed
1 month until next milestone

Study Start

First participant enrolled

March 15, 2017

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 15, 2022

Completed
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 15, 2023

Completed
Last Updated

January 16, 2019

Status Verified

January 1, 2019

Enrollment Period

4.8 years

First QC Date

February 1, 2017

Last Update Submit

January 10, 2019

Conditions

Outcome Measures

Primary Outcomes (9)

  • 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 Outcomes (4)

  • Clinical efficacy of lipid lowering treatment

    3years

  • Clinical safety of lipid lowering treatment

    3years

  • statin discontinuation and intolerance

    3years

  • Clinical adverse events

    3years

Study Arms (2)

High-intensity statin monotherapy

ACTIVE COMPARATOR

Statin monotherapy

Drug: Rosuvastatin

Statin plus ezetimibe combination therapy

EXPERIMENTAL

Statin plus ezetimibe combination therapy

Drug: Rosuvastatin plus ezetimibe

Interventions

Subjects will start rosuvastatin 20 mg a day irrespective of previous lipid-lowering treatment or LDL-cholesterol level as current US guideline.

High-intensity statin monotherapy

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.

Statin plus ezetimibe combination therapy

Eligibility Criteria

Age19 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine

Seoul, 03722, South Korea

RECRUITING

Related Publications (7)

  • Lee JH, Ahn SG, Jeon HS, Lee JW, Youn YJ, Lee YJ, Lee SJ, Hong SJ, Ahn CM, Ko YG, Kim JS, Choi D, Hong MK, Jang Y, Kim BK. Remnant cholesterol as a residual risk in atherosclerotic cardiovascular disease patients under statin-based lipid-lowering therapy: A post hoc analysis of the RACING trial. J Clin Lipidol. 2024 Nov-Dec;18(6):e905-e914. doi: 10.1016/j.jacl.2024.07.005. Epub 2024 Jul 27.

  • Kim BG, Lee SJ, Lee YJ, You SC, Hong SJ, Yun KH, Hong BK, Heo JH, Rha SW, Hong SJ, Ahn CM, Kim BK, Ko YG, Choi D, Hong MK, Jang Y, Cho YH, Kim JS. Effect of moderate-intensity statin with ezetimibe combination vs. high-intensity statin therapy according to sex in patients with atherosclerosis. Sci Rep. 2023 Nov 17;13(1):20157. doi: 10.1038/s41598-023-47505-x.

  • Lee SJ, Cha JJ, Choi WG, Lee WS, Jeong JO, Choi S, Cho YH, Park W, Yoon CH, Lee YJ, Hong SJ, Ahn CM, Kim BK, Ko YG, Choi D, Hong MK, Jang Y, Hong SJ, Kim JS; RACING Investigators. Moderate-Intensity Statin With Ezetimibe Combination Therapy vs High-Intensity Statin Monotherapy in Patients at Very High Risk of Atherosclerotic Cardiovascular Disease: A Post Hoc Analysis From the RACING Randomized Clinical Trial. JAMA Cardiol. 2023 Sep 1;8(9):853-858. doi: 10.1001/jamacardio.2023.2222.

  • Park JI, Lee SJ, Hong BK, Cho YH, Shin WY, Lim SW, Kang WC, Park Y, Lee SY, Lee YJ, Hong SJ, Ahn CM, Kim BK, Ko YG, Choi D, Hong MK, Jang Y, Kim JS; RACING investigators. Efficacy and safety of moderate-intensity statin with ezetimibe combination therapy in patients after percutaneous coronary intervention: a post-hoc analysis of the RACING trial. EClinicalMedicine. 2023 Apr 4;58:101933. doi: 10.1016/j.eclinm.2023.101933. eCollection 2023 Apr.

  • Lee SH, Lee YJ, Heo JH, Hur SH, Choi HH, Kim KJ, Kim JH, Park KH, Lee JH, Choi YJ, Lee SJ, Hong SJ, Ahn CM, Kim BK, Ko YG, Choi D, Hong MK, Jang Y, Kim JS. Combination Moderate-Intensity Statin and Ezetimibe Therapy for Elderly Patients With Atherosclerosis. J Am Coll Cardiol. 2023 Apr 11;81(14):1339-1349. doi: 10.1016/j.jacc.2023.02.007.

  • Lee YJ, Cho JY, You SC, Lee YH, Yun KH, Cho YH, Shin WY, Im SW, Kang WC, Park Y, Lee SY, Lee SJ, Hong SJ, Ahn CM, Kim BK, Ko YG, Choi D, Hong MK, Jang Y, Kim JS. Moderate-intensity statin with ezetimibe vs. high-intensity statin in patients with diabetes and atherosclerotic cardiovascular disease in the RACING trial. Eur Heart J. 2023 Mar 14;44(11):972-983. doi: 10.1093/eurheartj/ehac709.

  • 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.

MeSH Terms

Conditions

Cardiovascular DiseasesCerebrovascular Disorders

Interventions

Rosuvastatin CalciumEzetimibe

Condition Hierarchy (Ancestors)

Brain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular Diseases

Intervention Hierarchy (Ancestors)

SulfonamidesAmidesOrganic ChemicalsFluorobenzenesHydrocarbons, FluorinatedHydrocarbons, HalogenatedHydrocarbonsSulfonesSulfur CompoundsPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsAzetidinesAzetines

Central Study Contacts

Yang-Soo Jang, MD, PhD

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 1, 2017

First Posted

February 7, 2017

Study Start

March 15, 2017

Primary Completion

January 15, 2022

Study Completion

February 15, 2023

Last Updated

January 16, 2019

Record last verified: 2019-01

Data Sharing

IPD Sharing
Will not share

Locations