Clinical trial NCT03570697: Imaging of Coronary Plaques in Participants Treated With Evolocumab
Official title: High-Resolution Assessment of Coronary Plaques in a Global Evolocumab Randomized Study (HUYGENS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Coronary Artery Disease (CAD)
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
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2018-06-27
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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).

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.

Primary outcomes:
measure: Absolute Change From Baseline in Minimum FCT
timeFrame: Baseline, week 50
Secondary outcomes:
measure: Percent Change From Baseline in Minimum FCT
timeFrame: Baseline, week 50
measure: Absolute Change From Baseline in Mean Minimum FCT
timeFrame: Baseline, week 50
measure: Absolute Change From Baseline in the Maximum Lipid Arc
timeFrame: Baseline, week 50
measure: Absolute Change From Baseline in Minimum FCT in Lipid Rich Plaques
timeFrame: Baseline, week 50
measure: Absolute Change From Baseline in Maximum Lipid Arc in Lipid Rich Plaques
timeFrame: Baseline, week 50
measure: Absolute Change From Baseline in Lipid Core Length in Lipid Rich Plaques
timeFrame: Baseline, week 50
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California at Los Angeles
state: California
city: Washington
country: United States
facility: Medstar Heart and Vascular Institute
state: District of Columbia
city: Elkhart
country: United States
facility: Midwest Cardiovascular Research And Education Foundation
state: Indiana
city: Saint Louis
country: United States
facility: Saint Louis University Hospital
state: Missouri
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Epping
country: Australia
facility: The Northern Hospital
state: Victoria
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Berlin
country: Germany
facility: Charite UniversitÃ¤tsmedizin Berlin Campus Benjamin Franklin
city: Hamburg
country: Germany
facility: UniversitÃ¤res Herzzentrum Hamburg GmbH
city: MÃ¼nchen
country: Germany
facility: Deutsches Herzzentrum MÃ¼nchen des Freistaates Bayern
city: Balatonfured
country: Hungary
facility: Allami Szivkorhaz Balatonfured
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
city: Cuneo
country: Italy
facility: Azienda Ospedaliera Santa Croce e Carle
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Milano
country: Italy
facility: IRCCS Centro Cardiologico Monzino
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Roma
country: Italy
facility: Azienda Ospedaliera San Giovanni Addolorata
city: Rozzano MI
country: Italy
facility: IRCCS Istituto Clinico Humanitas
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgroep
city: Amsterdam
country: Netherlands
facility: Vrjie Universiteit Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
city: Nijmegen
country: Netherlands
facility: Canisius-Wilhelmina Ziekenhuis
city: Tilburg
country: Netherlands
facility: Elisabeth-TweeSteden Ziekenhuis
city: Zwolle
country: Netherlands
facility: Isala Klinieken
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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/
citation: 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.