AzTrials
AzTrials

Coronary Artery Disease (CAD)Phase 3NCT03570697

Imaging of Coronary Plaques in Participants Treated With Evolocumab

A Phase 3 study testing Evolocumab and Statin therapy in people with Coronary Artery Disease (CAD), run by Amgen at 33 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

To evaluate the effect of evolocumab on fibrous cap thickness (FCT) in participants with non-ST-elevation acute coronary syndrome (NSTE-ACS) who are taking maximally tolerated statin therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Coronary Artery Disease (CAD)
What is being tested?
Evolocumab and Statin therapy
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
164 participants
Where
33 sitesin 7 countries
Study dates
19 Nov 2018to 21 Jan 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Provided informed consent prior to initiation of any study-specific activities/procedures.
  • Age greater than or equal to 18 years at screening
  • Clinical indication for coronary angiography during admission due to NSTE-ACS with interventional treatment of culprit plaque
  • An eligible low-density lipoprotein cholesterol (LDL-C) level via local lab assessment based on statin use at screening
  • No statin use: greater than or equal to 130 mg/dL Low- or moderate-intensity statin use greater than or equal to 80 mg/dL High-intensity statin use greater than or equal to 60 mg/dL
  • On maximally tolerated statin therapy in accordance with standard of care per local guidelines prior to randomization.
Show all 18Show fewer
  • Tolerates placebo run-in injection at screening
  • Meets all the following criteria at the qualifying coronary angiogram:
  • Angiographic evidence of coronary artery disease (CAD) with greater than or equal to 20% reduction of lumen diameter by angiographic visual estimation, in addition to the culprit plaque.
  • Left main coronary artery must not have a greater than 50% reduction in lumen diameter by visual angiographic estimation.
  • Targeted vessel:
  • May not be the culprit vessel for the current or a previous myocardial infarction (MI).
  • Has not undergone prior percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), and may not be a bypass graft.
  • May not be a candidate for PCI or CABG currently or over the next 12 months, in the opinion of the investigator.
  • Must be accessible by the optical coherence tomography (OCT) catheter.
  • Targeted segment:
  • Must have up to 50% but not greater than 50% reduction in lumen diameter by visual angiographic estimation and must be at least 40 mm in length.
  • Must contain at least 1 image with a fibrous cap thickness (FCT) of less than or equal to 120 μm and at least 1 image with a lipid arc of greater than 90° as determined by the imaging core laboratory Distal plaques of up to 50% stenosis by visual angiographic estimation are permitted, provided that such stenosis is not a target for PCI or CABG.

Who cannot join

  • ST-segment elevation myocardial infarction (STEMI) or left bundle branch block (LBBB).
  • Acute coronary syndromes (ACS) likely to be caused by a non-atherosclerotic process, in the opinion of the investigator (ie, type 2 myocardial infarction, which is characterized by an imbalance between myocardial oxygen demand and supply).
  • Clinically significant heart disease which in the opinion of the investigator is likely to require coronary bypass surgery, PCI (does not apply to PCI of non-STEMI (NSTEMI) during initial screening angiogram), surgical or percutaneous valve repair and/or replacement during the course of the study.
  • Any cardiac surgery within 6 weeks prior to screening.
  • Triglycerides greater than or equal to 400 mg/dL (4.5 mmol/L) at screening.
  • Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73m^2 at screening.
Show all 16Show fewer
  • Malignancy except non-melanoma skin cancers, cervical, or breast ductal carcinoma in situ within the last 5 years.
  • Intolerant to statins as determined by principal investigator.
  • Previously received or receiving evolocumab or any other therapy to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9).
  • Previously received a cholesterol ester transfer protein (CETP) inhibitor (ie, anacetrapib, dalcetrapib, evacetrapib), mipomersen, lomitapide, or has undergone LDL-apheresis in the last 12 months prior to LDL-C screening.
  • Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
  • Baseline OCT does not meet OCT imaging criteria as determined by the imagine core laboratory technical standards.
  • Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 15 weeks after the last dose of investigational product. (Females of childbearing potential should only be included in the study after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test.)
  • Female subjects of childbearing potential unwilling to use 1 acceptable method of effective contraception during treatment and for an additional 15 weeks after the last dose of investigational product.
  • Female subject who has not used an acceptable method(s) of birth control for at least 1 month prior to screening, unless the female subject is sterilized or postmenopausal.
  • Known sensitivity to any of the products or components (eg, carboxymethylcellulose) to be administered during dosing.

Trial locations and contacts

33 sites in 7 countries.

33 sites in 7 countries

Italy7 sites

  • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

    Bergamo, 24127

  • Azienda Ospedaliera Santa Croce e Carle

    Cuneo, 12100

  • Azienda Ospedaliera Universitaria Careggi

    Florence, 50134

  • IRCCS Centro Cardiologico Monzino

    Milan, 20138

  • Azienda Ospedaliera Universitaria Federico II

    Naples, 80131

  • Azienda Ospedaliera San Giovanni Addolorata

    Roma, 00184

  • IRCCS Istituto Clinico Humanitas

    Rozzano MI, 20089

Other trials in Italy

Netherlands7 sites

  • Noordwest Ziekenhuisgroep

    Alkmaar, 1815 JD

  • Vrjie Universiteit Medisch Centrum

    Amsterdam, 1081 HV

  • Onze Lieve Vrouwe Gasthuis

    Amsterdam, 1091 AC

  • Radboud Universitair Medisch Centrum

    Nijmegen, 6525 GA

  • Canisius-Wilhelmina Ziekenhuis

    Nijmegen, 6532 SZ

  • Elisabeth-TweeSteden Ziekenhuis

    Tilburg, 5042 AD

  • Isala Klinieken

    Zwolle, 8025 AB

Other trials in Netherlands

United States5 sites

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

  • Midwest Cardiovascular Research And Education Foundation

    Elkhart, Indiana, 46514

  • University of California at Los Angeles

    Los Angeles, California, 90095

  • Saint Louis University Hospital

    St Louis, Missouri, 63110

  • Medstar Heart and Vascular Institute

    Washington D.C., District of Columbia, 20010

Other trials in United States

Australia5 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Royal Prince Alfred Hospital

    Camperdown, New South Wales, 2050

  • Monash Medical Centre

    Clayton, Victoria, 3168

  • The Northern Hospital

    Epping, Victoria, 3076

  • Royal North Shore Hospital

    St Leonards, New South Wales, 2065

Other trials in Australia

Hungary4 sites

  • Allami Szivkorhaz Balatonfured

    Balatonfüred, 8230

  • Semmelweis Egyetem

    Budapest, 1122

  • Magyar Honvedseg Egeszsegugyi Kozpont

    Budapest, 1134

  • Pecsi Tudomanyegyetem Klinikai Kozpont

    Pécs, 7624

Other trials in Hungary

Germany3 sites

  • Charite Universitätsmedizin Berlin Campus Benjamin Franklin

    Berlin, 12203

  • Universitäres Herzzentrum Hamburg GmbH

    Hamburg, 20246

  • Deutsches Herzzentrum München des Freistaates Bayern

    München, 80636

Other trials in Germany

Czechia2 sites

  • Fakultni nemocnice Brno

    Brno, 625 00

  • Fakultni nemocnice Hradec Kralove

    Hradec Králové, 500 05

Other trials in Czechia

About this study

Official title: High-Resolution Assessment of Coronary Plaques in a Global Evolocumab Randomized Study (HUYGENS)

To evaluate the effect of evolocumab on fibrous cap thickness (FCT) in participants with non-ST-elevation acute coronary syndrome (NSTE-ACS) who are taking maximally tolerated statin therapy.

Read the detailed description

This study seeks to identify morphologic changes, such as increase in FCT in atherosclerotic plaques associated with treatment with evolocumab and maximally tolerated statin therapy with or without additional lipid-modifying medication in patients presenting with NSTE-ACS using optical coherence tomography (OCT; primary, secondary, and exploratory endpoints).

Being tested
Evolocumab, Placebo, Statin therapy
Keywords
Optical coherence tomography (OCT), Intravascular ultrasound (IVUS), Coronary angiography, Coronary artery disease, Cardiovascular events, Coronary atherosclerotic plaques, Lipid-lowering therapy, Statin, Maximally tolerated statin therapy
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.

  • EvolocumabDrug

    Also called Repatha, AMG 145, EvoMab

    Participants will receive evolocumab (AMG 145) subcutaneous monthly.

  • PlaceboDrug

    Participants will receive matching placebo subcutaneous monthly.

  • Statin therapyDrug

    high-intensity statin treatment with atorvastatin ≥ 40 mg daily or equivalent as background therapy

    Investigators will up-titrate statin therapy to the maximally tolerated dose, in accordance with local guidelines, prior to randomization.

Study groups in NCT03570697
Study groupRoleWhat they receive
EvolocumabExperimentalParticipants receive evolocumab subcutaneous injection once every month (QM) for 48 weeks. As prescribed and provided by the investigator, participants will be treated with maximally tolerated statin therapy, not expected to change for the duration of the study participation.
Receives: Drug: Evolocumab; Drug: Statin therapy
PlaceboPlacebo comparatorParticipants receive placebo subcutaneous injection QM for 48 weeks. As prescribed and provided by the Investigator, participants will be treated with maximally tolerated statin therapy, not expected to change for the duration of the study participation.
Receives: Drug: Placebo; Drug: Statin therapy

What is being measured

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

  1. Absolute Change From Baseline in Minimum FCT

    Absolute change from baseline in minimum FCT in a matched segment of artery as determined by OCT. Minimum FCT for a participant is defined as the minimum of all minimum FCT measurements within each individual frame across all frames of that participant. Higher value of FCT indicates a better situation.

    Measured: Baseline, week 50

Secondary outcomes (6)

  1. Percent Change From Baseline in Minimum FCT

    Percent change from baseline in minimum FCT in a matched segment of artery as determined by OCT. Minimum FCT for a participant is defined as the minimum of all minimum FCT measurements within each individual frame across all frames of that participant. Higher value of FCT indicates a better situation.

    Measured: Baseline, week 50

  2. Absolute Change From Baseline in Mean Minimum FCT

    Absolute change from baseline in mean minimum FCT for all images assessed in an individual participant as determined by OCT. Minimum FCT for a participant is defined as the minimum of all minimum FCT measurements within each individual frame across all frames of that participant. Higher value of FCT indicates a better situation.

    Measured: Baseline, week 50

  3. Absolute Change From Baseline in the Maximum Lipid Arc

    Absolute change from baseline in the maximum lipid arc in a matched segment of artery as determined by OCT. Lower value of lipid arc indicates a better situation.

    Measured: Baseline, week 50

  4. Absolute Change From Baseline in Minimum FCT in Lipid Rich Plaques

    Absolute change from baseline in minimum FCT in lipid rich plaques as determined by OCT. Lipid rich plaques are defined as minimum FCT less than 120 μm and lipid arc greater than 90° in at least 3 consecutive images as determined by OCT. Higher value of FCT indicates a better situation

    Measured: Baseline, week 50

  5. Absolute Change From Baseline in Maximum Lipid Arc in Lipid Rich Plaques

    Absolute change from baseline in maximum lipid arc in lipid rich plaques. Lipid rich plaques are defined as minimum FCT less than 120 μm and lipid arc greater than 90° in at least 3 consecutive images as determined by OCT. Lower value of lipid arc indicates a better situation.

    Measured: Baseline, week 50

  6. Absolute Change From Baseline in Lipid Core Length in Lipid Rich Plaques

    Absolute change from baseline in lipid core length in lipid rich plaques. Lipid rich plaques are defined as minimum FCT less than 120 μm and lipid arc greater than 90° in at least 3 consecutive images as determined by OCT. Lower value of lipid core length indicates a better situation.

    Measured: Baseline, week 50

Timeline

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

  1. First posted27 Jun 2018
  2. Study start19 Nov 2018
  3. Primary completion18 Dec 2020
  4. Study completion21 Jan 2021

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
164 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03570697
Sponsor's protocol ID
20160184
Other IDs
2017-003236-37, 2017
Status last verified
Apr 2022
First submitted
18 Jun 2018
Last updated
3 May 2022
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Publications

  • Nicholls SJ, Nissen SE, Prati F, Windecker S, Kataoka Y, Puri R, Hucko T, Kassahun H, Liao J, Somaratne R, Butters J, Di Giovanni G, Jones S, Psaltis PJ. Assessing the impact of PCSK9 inhibition on coronary plaque phenotype with optical coherence tomography: rationale and design of the randomized, placebo-controlled HUYGENS study. Cardiovasc Diagn Ther. 2021 Feb;11(1):120-129. doi: 10.21037/cdt-20-684.

    PubMed 33708484

  • Pharmacoeconomic Review Report: Icosapent Ethyl (Vascepa): (HLS Therapeutics Inc.): Indication: Prevention of cardiovascular events in statin-treated patients [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2020 Aug. Available from http://www.ncbi.nlm.nih.gov/books/NBK566010/

    PubMed 33355725

  • Di Giovanni G, Fujino M, Kataoka Y, Butters J, Hucko T, Puri R, Nissen SE, Nelson AJ, Psaltis PJ, Nicholls SJ. Impact of evolocumab on plaque phenotypic changes in patients with acute coronary syndrome and elevated lipoprotein(a) levels: a HUYGENS secondary analysis. Eur J Prev Cardiol. 2025 Apr 8:zwaf211. doi: 10.1093/eurjpc/zwaf211. Online ahead of print.

    PubMed 40424182

  • Fujino M, Di Giovanni G, Butters Bhsc J, Kataoka Y, Hucko T, Nelson AJ, Nissen SE, Psaltis PJ, Nicholls SJ. Achieved levels of apolipoprotein B and plaque composition after acute coronary syndromes: Insights from HUYGENS. Atherosclerosis. 2025 Apr;403:119145. doi: 10.1016/j.atherosclerosis.2025.119145. Epub 2025 Feb 20.

    PubMed 40020597

  • Nicholls SJ, Kataoka Y, Nissen SE, Prati F, Windecker S, Puri R, Hucko T, Aradi D, Herrman JR, Hermanides RS, Wang B, Wang H, Butters J, Di Giovanni G, Jones S, Pompili G, Psaltis PJ. Effect of Evolocumab on Coronary Plaque Phenotype and Burden in Statin-Treated Patients Following Myocardial Infarction. JACC Cardiovasc Imaging. 2022 Jul;15(7):1308-1321. doi: 10.1016/j.jcmg.2022.03.002. Epub 2022 Mar 16.

    PubMed 35431172

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Evolocumab and Statin therapy in people with Coronary Artery Disease (CAD), run by Amgen at 33 sites in 7 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 18 inclusion and 16 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: finished, as of the sponsor's last update on 3 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in Italy, Netherlands, United States, Australia, Hungary and 2 more countries. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Absolute Change From Baseline in Minimum FCT (time frame: Baseline, week 50). 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 NCT03570697, which also lists 5 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 3 May 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in