Intensive Lipid-lowering for Plaque and Major Adverse Cardiovascular Events in Low to Intermediate 10-year ASCVD Risk Population (ILLUMINATION)

April 25, 2023 updated by: Bin Lu, Chinese Academy of Medical Sciences, Fuwai Hospital

Effects of Intensive Lipid-lowering on Coronary Atherosclerotic Plaque Phenotype and Major Adverse Cardiovascular Events in Adults With Low to Intermediate 10-year ASCVD Risk: a Prospective, Randomized, Open-label, Blinded Endpoint Analysis(PROBE)

Current guidelines recommend moderate-intensity lipid-lowering therapy (goal for LDL-C <2.6 mmol/L or 30%-50% reduction from baseline) for patients with intermediate 10-year ASCVD risk. In these patients, early coronary atherosclerotic plaques (luminal stenosis<50%) detected by coronary CT angiography are common, but further interventions are lacking. This study aims to analyze whether intensive lipid-lowering therapy (goal for LDL-C <1.8 mmol/L or ≥50% reduction from baseline) could delay the progression of coronary atherosclerotic lesions and reduce the adverse cardiovascular events in these target patients.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Both American (2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease) and European (2019 ESC/EAS Guidelines for the management of dyslipidemias) guidelines currently recommended moderate-intensity lipid-lowering (goal for LDL-C <2.6 mmol/L or 30%-50% reduction from baseline) for primary prevention in the population at intermediate (or borderline) 10-year ASCVD risk, but the residual risk in this group of the population remains to be explored, especially in a subset with only nonobstructive atherosclerotic plaques(luminal stenosis<50%) detected by CCTA, for whom further risk stratification and precise interventions for primary prevention are lacking.

CCTA could show accurate images of patients' early coronary atherosclerotic lesions, and provides a wealth of image-based anatomical and functional information including plaque burden (total plaque volume, calcification score, segment involvement score, etc.), plaque composition, high-risk plaque characteristics, luminal stenosis, and CT-FFR. With this complete imaging information on CCTA, there is an urgent need to investigate primary prevention strategies and the evidence-based rationale for performing precise risk stratification in low to intermediate risk populations with nonobstructive coronary atherosclerotic lesions using CCTA.

A prospective, randomized, open-label, blinded endpoint analysis (PROBE) will be conducted in the population at clinical low to intermediate 10-year ASCVD risk with nonobstructive coronary atherosclerotic lesions, predominantly non-calcified plaques detected by CCTA. And the purpose of this study is to demonstrate that intensive lipid-lowering could slow down plaque progression and reduce the incidence of MACE in the target population, which provides an evidence-based rationale for further risk re-stratification. Enrolled people will be randomized into the intervention group (goal for LDL-C <1.8 mmol/L or ≥50% reduction from baseline) and control group (goal for LDL-C <2.6 mmol/L or 30%-50% reduction from baseline).

Study Type

Interventional

Enrollment (Anticipated)

2900

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China
        • Recruiting
        • Fuwai Hospital
        • Contact:
          • Bin Lu, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age 40-75 years
  2. Low to Intermediate 10-year atherosclerotic cardiovascular disease (ASCVD) risk by using pooled cohort equations (PCE).
  3. Coronary CT angiography shows atherosclerotic plaque in the main coronary vessels (>2mm diameter) with luminal stenosis <50%

Exclusion Criteria:

  1. Combination with serious cardiovascular diseases, including

    1. Heart failure (ejection fraction <30%)
    2. Arrhythmias (persistent atrial flutter/atrial fibrillation, second-degree or third-degree atrioventricular block)
    3. Hemodynamically important valvular disease
    4. Hemodynamically important congenital heart disease
    5. Stroke
  2. Myocardial infarction, coronary revascularization, or severe/unstable angina before or within 1 month of screening
  3. Active liver disease or hepatic dysfunction (defined as alanine aminotransferase or aspartate aminotransferase> 3 times the upper limit of normal)
  4. Unexplained creatine phosphokinase> 6 times the upper limit of normal
  5. Nephrotic syndrome
  6. Diabetes mellitus
  7. Uncontrollable hypertension
  8. Uncontrollable hypothyroidism
  9. Hypersensitivity to statins
  10. Any planned surgical procedure for the treatment of atherosclerosis
  11. Gastrointestinal diseases affecting drug absorption or history of gastrointestinal surgery
  12. Survival-limiting diseases
  13. Concurrent long-term immunosuppressive therapy
  14. Participation in another clinical trial concurrently or within 30 days before screening
  15. Pregnant or breastfeeding
  16. Other unsuitable situations deemed by physicians

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: intensive lipid-lowering group
Goal for LDL-C <1.8 mmol/L or ≥50% reduction from baseline.
Drug: Intensive lipid-lowering control
The initial recommended therapy is 10-20mg atorvastatin plus Ezetimibe, and the type and dosage of drugs can be adjusted according to the situation.
Other Names:
  • Lower goal for reducing LDL-C
Active Comparator: moderate-intensity lipid-lowering group
Goal for LDL-C <2.6 mmol/L or 30%-50% reduction from baseline.
Drug: Moderate-intensity lipid-lowering control
The initial recommended therapy is 10-20mg atorvastatin, and the type and dosage of drugs can be adjusted according to the situation.
Other Names:
  • Standard goal for reducing LDL-C

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Adverse Cardiovascular Events (MACE)
Time Frame: Within 3 years after the enrollment
Composite of all-cause death, non-fatal MI, non-fatal stroke, any revascularization, and hospitalization for angina
Within 3 years after the enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in coronary total plaque volume(mm³) on CCTA
Time Frame: Within 3 years after the enrollment
Total plaque volume(mm³) is defined as the sum of all plaque volumes for coronary arteries.
Within 3 years after the enrollment
Change in coronary plaque burden(%) on CCTA
Time Frame: Within 3 years after the enrollment
Plaque burden(%)=(plaque area/vessel area)×100%
Within 3 years after the enrollment
Changes in coronary plaque compositions(mm³, %) on CCTA
Time Frame: Within 3 years after the enrollment
Plaque compositions include lipid(<30 HU), fibrous(30-150HU), and calcified plaque(>350HU).
Within 3 years after the enrollment
Changes in coronary high-risk plaque characteristics on CCTA
Time Frame: Within 3 years after the enrollment
High-risk plaque characteristics are defined as positive remodeling(remodeling index, >1.1), low CT attenuation (mean CT number <30 HU), spotty calcification(punctate calcium within a plaque measuring less than 3 mm in all dimensions), or napkin-ring sign (a ringlike peripheral higher attenuation with central low CT attenuation).
Within 3 years after the enrollment
Change in coronary artery calcium score (CACS) on CT
Time Frame: Within 3 years after the enrollment
CACS is a quantification of all coronary calcification by the scoring algorithm proposed by Agatston et al.
Within 3 years after the enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese Academy of Medical Sciences, Fuwai Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 10, 2022

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2025

Study Registration Dates

First Submitted

July 7, 2022

First Submitted That Met QC Criteria

July 13, 2022

First Posted (Actual)

July 18, 2022

Study Record Updates

Last Update Posted (Actual)

April 27, 2023

Last Update Submitted That Met QC Criteria

April 25, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-CXGC03-3

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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