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Coronary Artery DiseaseFLAVOUR IVNCT06863545

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

A study testing PCSK9 inhibitors and background lipid-modifying therapy and Standard lipid-modifying therapy in people with Coronary Artery Disease and CT Angiography, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 6 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Coronary Artery Disease, CT Angiography, PCSK9
What is being tested?
PCSK9 inhibitors and background lipid-modifying therapy and Standard lipid-modifying therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3,596 participants
Where
6 sitesin 2 countries
Study dates
22 Apr 2025to Apr 2033
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject must be ≥ 18 years.
  • Patients with at least one target lesion meet CCTA-detected plaque features of the following:
  • Degree of stenosis ≥ 50% or plaque burden ≥ 70%
  • At least 2 of the following high-risk plaque features:
  • Low-attenuation plaque ii. Positive remodeling iii. Napkin-ring sign iv. Spotty calcium
  • The target lesion is located at the proximal or mid segment of left anterior descending artery, left circumflex artery or right coronary artery.
  • 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.

Who cannot join

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

Trial locations and contacts

6 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Xinyang Hu contact

+86 0571 87784808

hxy0507@126.com

Jian'an Wang contact

+86 0571 87784808

wangjianan111@zju.edu.cn

6 sites in 2 countries

China5 sites, 5 recruiting

  • Zhejiang Provincial Hospital of Traditional Chinese Medicine

    Hangzhou, Zhejiang

    Maosheng Xu

    Recruiting

  • Hangzhou Linping First People's Hospital

    Hangzhou

    Hong Yuan

    Recruiting

  • The Second Affiliated Hospital, School of Medicine, Zhejiang University

    Hangzhou

    Xinyang Hu, +86 0571 87784808, hxy0507@126.com

    Xinyang Hu

    Recruiting

  • Zhejiang Hospital

    Hangzhou

    Wei Mao

    Recruiting

  • Jinhua Central Hospital

    Jinhua

    Yibin Pan

    Recruiting

Other trials in China

South Korea1 site, 1 recruiting

  • Seoul National University Hospital

    Seoul

    Bon-Kwon Koo, MD, 82-2-2072-2062, bkkoo@snu.ac

    Not yet recruiting

Other trials in South Korea

About this study

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.

Read the 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.

Being tested
PCSK9 inhibitors and background lipid-modifying therapy, Standard lipid-modifying therapy
Keywords
PCSK9 inhibitors, Lipid-lowering therapy, High-Risk Coronary Plaques, Coronary CT angiography
Medical subject headings
Coronary Artery Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PCSK9 inhibitors and background lipid-modifying therapyDrug

    Patients will receive subcutaneous injections of PCSK9 inhibitors and oral administration of background LMT (including statins and/or cholesterol absorption inhibitors) for the first 12 months after randomization, with PCSK9 inhibitors administered every 2 weeks. After the first 12 months, patients will discontinue the PCSK9 inhibitors but continue background LMT for the remainder of the trial.

  • Standard lipid-modifying therapyDrug

    Patients will receive standard LMT commonly used in clinical practice.

Study groups in NCT06863545
Study groupRoleWhat they receive
PCSK9 inhibitors plus background lipid-modifying therapyExperimentalPatients 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.
Standard lipid-modifying therapyActive comparatorPatients will receive standard LMT commonly used in clinical practice.
Receives: Drug: Standard lipid-modifying therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Major adverse cardiac and cerebrovascular events (MACCEs)

    A composite of death from any cause, myocardial infarction (MI), coronary revascularization, or stroke.

    Measured: 24 months after the last patient's randomization

Secondary outcomes (10)

  1. MACCEs

    a composite of death from any cause, MI, coronary revascularization, or stroke.

    Measured: 60 months after the last patient's randomization

  2. Individual component of MACCEs.

    Individual component of MACCEs (death from any cause, MI, coronary revascularization, or stroke)

    Measured: 24 and 60 months after the last patient's randomization

  3. Major adverse cardiovascular events (MACEs)

    Defined as a composite of death from any cause, MI, coronary revascularization.

    Measured: 24 and 60 months after the last patient's randomization

  4. Target vessel failure (TVF)

    Defined as a composite of cardiac death, target-vessel MI, or target vessel revascularization

    Measured: 24 and 60 months after the last patient's randomization

  5. Cost-effectiveness analysis

    Cost-effectiveness analysis

    Measured: 24 and 60 months after the last patient's randomization

  6. All-cause and cardiac death.

    All-cause and cardiac death.

    Measured: 24 and 60 months after the last patient's randomization

  7. Any target-vessel MI.

    Any target-vessel MI.

    Measured: 24 and 60 months after the last patient's randomization

  8. Any target vessel revascularization.

    Any target vessel revascularization.

    Measured: 24 and 60 months after the last patient's randomization

  9. Any coronary revascularization (ischemia-driven or all).

    Any coronary revascularization (ischemia-driven or all).

    Measured: 24 and 60 months after the last patient's randomization

  10. CT coronary angiography findings

    Changes in the CT-derived fractional flow reserve, lumen, plaque quantity and quality between baseline.

    Measured: 36 months after the last patient's randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Mar 2025
  2. Study start22 Apr 2025
  3. Primary completionApr 2030 (estimated)
  4. Study completionApr 2033 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
3,596 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06863545
Sponsor's protocol ID
2025-0052
Acronym
FLAVOUR IV
Status last verified
Feb 2026
First submitted
3 Mar 2025
Last updated
6 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The deidentified data will be shared after publication of first manuscript.

Publications

  • Iatan I, Guan M, Humphries KH, Yeoh E, Mancini GBJ. Atherosclerotic Coronary Plaque Regression and Risk of Adverse Cardiovascular Events: A Systematic Review and Updated Meta-Regression Analysis. JAMA Cardiol. 2023 Oct 1;8(10):937-945. doi: 10.1001/jamacardio.2023.2731.

    PubMed 37647074

  • Nicholls SJ, Puri R, Anderson T, Ballantyne CM, Cho L, Kastelein JJ, Koenig W, Somaratne R, Kassahun H, Yang J, Wasserman SM, Scott R, Ungi I, Podolec J, Ophuis AO, Cornel JH, Borgman M, Brennan DM, Nissen SE. Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial. JAMA. 2016 Dec 13;316(22):2373-2384. doi: 10.1001/jama.2016.16951.

    PubMed 27846344

  • Raber L, Ueki Y, Otsuka T, Losdat S, Haner JD, Lonborg J, Fahrni G, Iglesias JF, van Geuns RJ, Ondracek AS, Radu Juul Jensen MD, Zanchin C, Stortecky S, Spirk D, Siontis GCM, Saleh L, Matter CM, Daemen J, Mach F, Heg D, Windecker S, Engstrom T, Lang IM, Koskinas KC; PACMAN-AMI collaborators. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial. JAMA. 2022 May 10;327(18):1771-1781. doi: 10.1001/jama.2022.5218.

    PubMed 35368058

  • Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR; FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017 May 4;376(18):1713-1722. doi: 10.1056/NEJMoa1615664. Epub 2017 Mar 17.

    PubMed 28304224

  • Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Lecorps G, Mahaffey KW, Moryusef A, Pordy R, Quintero K, Roe MT, Sasiela WJ, Tamby JF, Tricoci P, White HD, Zeiher AM; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018 Nov 29;379(22):2097-2107. doi: 10.1056/NEJMoa1801174. Epub 2018 Nov 7.

    PubMed 30403574

  • Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, Banning AP, Budaj A, Buechel RR, Chiariello GA, Chieffo A, Christodorescu RM, Deaton C, Doenst T, Jones HW, Kunadian V, Mehilli J, Milojevic M, Piek JJ, Pugliese F, Rubboli A, Semb AG, Senior R, Ten Berg JM, Van Belle E, Van Craenenbroeck EM, Vidal-Perez R, Winther S; ESC Scientific Document Group. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024 Sep 29;45(36):3415-3537. doi: 10.1093/eurheartj/ehae177. No abstract available.

    PubMed 39210710

  • Virani SS, Newby LK, Arnold SV, Bittner V, Brewer LC, Demeter SH, Dixon DL, Fearon WF, Hess B, Johnson HM, Kazi DS, Kolte D, Kumbhani DJ, LoFaso J, Mahtta D, Mark DB, Minissian M, Navar AM, Patel AR, Piano MR, Rodriguez F, Talbot AW, Taqueti VR, Thomas RJ, van Diepen S, Wiggins B, Williams MS; Peer Review Committee Members. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2023 Aug 29;148(9):e9-e119. doi: 10.1161/CIR.0000000000001168. Epub 2023 Jul 20.

    PubMed 37471501

  • Yang S, Hoshino M, Yonetsu T, Zhang J, Hwang D, Shin ES, Doh JH, Nam CW, Wang J, Chen S, Tanaka N, Matsuo H, Kubo T, Chang HJ, Kakuta T, Koo BK. Outcomes of non-ischaemic coronary lesions with high-risk plaque characteristics on coronary CT angiography. EuroIntervention. 2023 Jan 23;18(12):1011-1021. doi: 10.4244/EIJ-D-22-00562.

    PubMed 36222756

  • Lee JM, Choi KH, Koo BK, Park J, Kim J, Hwang D, Rhee TM, Kim HY, Jung HW, Kim KJ, Yoshiaki K, Shin ES, Doh JH, Chang HJ, Cho YK, Yoon HJ, Nam CW, Hur SH, Wang J, Chen S, Kuramitsu S, Tanaka N, Matsuo H, Akasaka T. Prognostic Implications of Plaque Characteristics and Stenosis Severity in Patients With Coronary Artery Disease. J Am Coll Cardiol. 2019 May 21;73(19):2413-2424. doi: 10.1016/j.jacc.2019.02.060.

    PubMed 31097161

  • Ferencik M, Mayrhofer T, Bittner DO, Emami H, Puchner SB, Lu MT, Meyersohn NM, Ivanov AV, Adami EC, Patel MR, Mark DB, Udelson JE, Lee KL, Douglas PS, Hoffmann U. Use of High-Risk Coronary Atherosclerotic Plaque Detection for Risk Stratification of Patients With Stable Chest Pain: A Secondary Analysis of the PROMISE Randomized Clinical Trial. JAMA Cardiol. 2018 Feb 1;3(2):144-152. doi: 10.1001/jamacardio.2017.4973.

    PubMed 29322167

  • Williams MC, Moss AJ, Dweck M, Adamson PD, Alam S, Hunter A, Shah ASV, Pawade T, Weir-McCall JR, Roditi G, van Beek EJR, Newby DE, Nicol ED. Coronary Artery Plaque Characteristics Associated With Adverse Outcomes in the SCOT-HEART Study. J Am Coll Cardiol. 2019 Jan 29;73(3):291-301. doi: 10.1016/j.jacc.2018.10.066.

    PubMed 30678759

  • SCOT-HEART Investigators; Newby DE, Adamson PD, Berry C, Boon NA, Dweck MR, Flather M, Forbes J, Hunter A, Lewis S, MacLean S, Mills NL, Norrie J, Roditi G, Shah ASV, Timmis AD, van Beek EJR, Williams MC. Coronary CT Angiography and 5-Year Risk of Myocardial Infarction. N Engl J Med. 2018 Sep 6;379(10):924-933. doi: 10.1056/NEJMoa1805971. Epub 2018 Aug 25.

    PubMed 30145934

  • Virmani R, Burke AP, Kolodgie FD, Farb A. Pathology of the thin-cap fibroatheroma: a type of vulnerable plaque. J Interv Cardiol. 2003 Jun;16(3):267-72. doi: 10.1034/j.1600-0854.2003.8042.x.

    PubMed 12800406

  • Koo BK, Hu X, Kang J, Zhang J, Jiang J, Hahn JY, Nam CW, Doh JH, Lee BK, Kim W, Huang J, Jiang F, Zhou H, Chen P, Tang L, Jiang W, Chen X, He W, Ahn SG, Yoon MH, Kim U, Lee JM, Hwang D, Ki YJ, Shin ES, Kim HS, Tahk SJ, Wang J; FLAVOUR Investigators. Fractional Flow Reserve or Intravascular Ultrasonography to Guide PCI. N Engl J Med. 2022 Sep 1;387(9):779-789. doi: 10.1056/NEJMoa2201546.

    PubMed 36053504

Questions about this trial

What is this clinical trial studying?

A study testing PCSK9 inhibitors and background lipid-modifying therapy and Standard lipid-modifying therapy in people with Coronary Artery Disease and CT Angiography, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in China, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Xinyang Hu (+86 0571 87784808, hxy0507@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Major adverse cardiac and cerebrovascular events (MACCEs) (time frame: 24 months after the last patient's randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06863545, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2026.

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