Imaging of Coronary Plaques in Participants Treated With Evolocumab
Coronary Artery Disease (CAD)
About this trial
This is an interventional treatment trial for Coronary Artery Disease (CAD) focused on measuring 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
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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.
- 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.
Sites / Locations
- University of California at Los Angeles
- Medstar Heart and Vascular Institute
- Midwest Cardiovascular Research And Education Foundation
- Saint Louis University Hospital
- University Hospitals Cleveland Medical Center
- Royal Prince Alfred Hospital
- Royal North Shore Hospital
- Royal Adelaide Hospital
- Monash Medical Centre
- The Northern Hospital
- Fakultni nemocnice Brno
- Fakultni nemocnice Hradec Kralove
- Charite Universitätsmedizin Berlin Campus Benjamin Franklin
- Universitäres Herzzentrum Hamburg GmbH
- Deutsches Herzzentrum München des Freistaates Bayern
- Allami Szivkorhaz Balatonfured
- Semmelweis Egyetem
- Magyar Honvedseg Egeszsegugyi Kozpont
- Pecsi Tudomanyegyetem Klinikai Kozpont
- Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
- Azienda Ospedaliera Santa Croce e Carle
- Azienda Ospedaliera Universitaria Careggi
- IRCCS Centro Cardiologico Monzino
- Azienda Ospedaliera Universitaria Federico II
- Azienda Ospedaliera San Giovanni Addolorata
- IRCCS Istituto Clinico Humanitas
- Noordwest Ziekenhuisgroep
- Vrjie Universiteit Medisch Centrum
- Onze Lieve Vrouwe Gasthuis
- Radboud Universitair Medisch Centrum
- Canisius-Wilhelmina Ziekenhuis
- Elisabeth-TweeSteden Ziekenhuis
- Isala Klinieken
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Evolocumab
Placebo
Participants 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.
Participants 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.