Further Lipid-Lowering With PCSK9 Inhibitors for Cardiovascular Outcomes in High-Risk Coronary Plaques Assessed by CT Angiography (FLAVOUR IV)

February 3, 2026 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University
The primary objective was to evaluate the effect of PCSK9 inhibitors in addition to the background lipid-modifying therapy (LMT), compared with standard LMT in terms of clinical outcomes in patients with coronary CT angiography (CCTA)-detected high-risk plaques.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

CCTA is an accurate, noninvasive alternative to invasive coronary angiography. CCTA can provide detailed information about the characteristics of coronary artery plaques, such as their composition, morphology, and distribution. Various CCTA-detected plaque characteristics indicative of plaque quantity and quality have been identified as high-risk features independently predicting clinical events, including the presence of positive remodeling, low attenuation plaque, spotty calcification, and napkin ring sign. Currently, the treatment for CCTA-detected high-risk plaque has been receiving increasing interest. The current study aimed to prove the efficacy of PCSK9 inhibitors in addition to the background LMT, as compared with standard LMT in patients with CCTA-detected high-risk plaques.

Hypothesis: PCSK9 inhibitors in addition to background LMT will show a superior event rate, compared with standard LMT, in terms of major adverse cardiac and cerebrovascular events (MACCEs) at 24 months after the last patient's randomization in patients with high-risk coronary plaques assessed by CT Angiography.

Study Type

Interventional

Enrollment (Estimated)

3596

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 Contact Backup

Study Locations

  • China
      • Hangzhou, China
        • Recruiting
        • The Second Affiliated Hospital, School of Medicine, Zhejiang University
        • Contact:
        • Principal Investigator:
          • Xinyang Hu
      • Hangzhou, China
        • Recruiting
        • Hangzhou Linping First People's Hospital
        • Contact:
          • Hong Yuan
      • Hangzhou, China
        • Recruiting
        • Zhejiang Hospital
        • Contact:
          • Wei Mao
      • Jinhua, China
        • Recruiting
        • Jinhua Central Hospital
        • Contact:
          • Yibin Pan
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • Recruiting
        • Zhejiang Provincial Hospital of Traditional Chinese Medicine
        • Contact:
          • Maosheng Xu
  • South Korea
      • Seoul, South Korea
        • Not yet recruiting
        • Seoul National University Hospital
        • Contact:
          • Bon-Kwon Koo, MD
          • Phone Number: 82-2-2072-2062
          • Email: bkkoo@snu.ac

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Subject must be ≥ 18 years.

  2. Patients with at least one target lesion meet CCTA-detected plaque features of the following:

    1. Degree of stenosis ≥ 50% or plaque burden ≥ 70%
    2. At least 2 of the following high-risk plaque features:

    i. Low-attenuation plaque ii. Positive remodeling iii. Napkin-ring sign iv. Spotty calcium

  3. The target lesion is located at the proximal or mid segment of left anterior descending artery, left circumflex artery or right coronary artery.
  4. Subject is able to confirm his/her understanding of the risks, benefits, and treatment alternatives of receiving study-related treatment. He/she or his/her legally authorized representative provides written informed consent prior to any study-related procedure.

Exclusion Criteria:

  1. Target lesions underwent or planned to revascularization.
  2. Patients with acute coronary syndrome.
  3. New York Heart Association class III or IV, or last known left ventricular ejection fraction < 30%.
  4. Uncontrolled or recurrent ventricular tachycardia.
  5. Homozygous familial hypercholesterolemia.
  6. Active liver disease or hepatic dysfunction.
  7. Failed CCTA plaque analysis.
  8. Non-cardiac co-morbid conditions with life expectancy < 2 years.
  9. Pregnant and/or lactating women.
  10. Known hypersensitivity or contraindication to statin or PCSK9 inhibitors.

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PCSK9 inhibitors plus background lipid-modifying therapy
Patients will receive PCSK9 inhibitors treatment and background lipid-modifying therapy for the first 12 months after randomization, and then continue background lipid-modifying therapy for the remainder of the trial.
Drug: PCSK9 inhibitors and background lipid-modifying therapy
  1. Initial Treatment Phase (First 12 months) Patients will receive subcutaneous injections of PCSK9 inhibitors and background LMT for the first 12 months after randomization, with PCSK9 inhibitors administered every 2 weeks. For those already on background LMT (including statins and/or cholesterol absorption inhibitors), current treatment will be continued. Patients without background LMT will start an initial regimen, defined as atorvastatin 20 mg or rosuvastatin 10 mg.
  2. Maintenance Phase (After First 12 months) Patients will discontinue the PCSK9 inhibitors but continue background LMT for the remainder of the trial.
Active Comparator: Standard lipid-modifying therapy
Patients will receive standard LMT commonly used in clinical practice.
Drug: Standard lipid-modifying therapy
Patients will receive standard LMT commonly used in clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major adverse cardiac and cerebrovascular events (MACCEs)
Time Frame: 24 months after the last patient's randomization
A composite of death from any cause, myocardial infarction (MI), coronary revascularization, or stroke.
24 months after the last patient's randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MACCEs
Time Frame: 60 months after the last patient's randomization
a composite of death from any cause, MI, coronary revascularization, or stroke.
60 months after the last patient's randomization
Individual component of MACCEs.
Time Frame: 24 and 60 months after the last patient's randomization
Individual component of MACCEs (death from any cause, MI, coronary revascularization, or stroke)
24 and 60 months after the last patient's randomization
Major adverse cardiovascular events (MACEs)
Time Frame: 24 and 60 months after the last patient's randomization
Defined as a composite of death from any cause, MI, coronary revascularization.
24 and 60 months after the last patient's randomization
Target vessel failure (TVF)
Time Frame: 24 and 60 months after the last patient's randomization
Defined as a composite of cardiac death, target-vessel MI, or target vessel revascularization
24 and 60 months after the last patient's randomization
Cost-effectiveness analysis
Time Frame: 24 and 60 months after the last patient's randomization
Cost-effectiveness analysis
24 and 60 months after the last patient's randomization
All-cause and cardiac death.
Time Frame: 24 and 60 months after the last patient's randomization
All-cause and cardiac death.
24 and 60 months after the last patient's randomization
Any target-vessel MI.
Time Frame: 24 and 60 months after the last patient's randomization
Any target-vessel MI.
24 and 60 months after the last patient's randomization
Any target vessel revascularization.
Time Frame: 24 and 60 months after the last patient's randomization
Any target vessel revascularization.
24 and 60 months after the last patient's randomization
Any coronary revascularization (ischemia-driven or all).
Time Frame: 24 and 60 months after the last patient's randomization
Any coronary revascularization (ischemia-driven or all).
24 and 60 months after the last patient's randomization
CT coronary angiography findings
Time Frame: 36 months after the last patient's randomization
Changes in the CT-derived fractional flow reserve, lumen, plaque quantity and quality between baseline.
36 months after the last patient's randomization

Collaborators and Investigators

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

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Investigators

  • Principal Investigator: Xinyang Hu, Second Affiliated Hospital, School of Medicine, Zhejiang University
  • Principal Investigator: Bon-Kwon Koo, Seoul National University 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

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)

April 22, 2025

Primary Completion (Estimated)

April 1, 2030

Study Completion (Estimated)

April 1, 2033

Study Registration Dates

First Submitted

March 3, 2025

First Submitted That Met QC Criteria

March 3, 2025

First Posted (Actual)

March 7, 2025

Study Record Updates

Last Update Posted (Actual)

February 6, 2026

Last Update Submitted That Met QC Criteria

February 3, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-0052

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The deidentified data will be shared after publication of first manuscript.

IPD Sharing Time Frame

Data will be available within 12 months of study completion.

IPD Sharing Access Criteria

Data access requests will be reviewed by an external Independent Review Panel. Requestors will be required to sign a Data Access Agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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