Clinical trial NCT04710368: Effect of Evolocumab on Coronary Plaque Characteristics
Official title: Effect of Evolocumab on Coronary Plaque Characteristics: a Multimodality Imaging Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: Coronary Artery Disease
Coronary Plaque
Optical Coherence Tomography
Near-Infrared Spectroscopy
Evolocumab
Statin
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2021-01-14
Enrollment: 137
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The study team will screen patients scheduled for elective PCI, who are receiving statin therapy for at least 4 weeks with acceptable LDL-C levels. Patients with non-obstructive lesion (30-50% stenosis) by angiography and lipid-rich plaque with lipid arc \>90° and minimal fibrous cap thickness ≤ 120 µm detected by OCT will comprise the final study population. Serial NIRS/IVUS and OCT imaging will be performed in a non-target lesions, first during PCI and subsequently after 26 weeks.
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of the study is to assess the effect of evolocumab on coronary plaque morphology using intravascular imaging and gene expression analysis of peripheral blood mononuclear cells (PBMC) in patients with stable CAD on maximally tolerated statin therapy. The study combines multi-modality intravascular imaging approaches and transcriptomic based machine learning algorithms to uncover molecular mechanisms responsible for the beneficial changes in atherosclerotic lesions of patients treated with evolocumab. The primary end-points are the changes from baseline to follow-up in (1) the minimal fibrous cap thickness (FCT) assessed by optical coherence tomography (OCT) and (2) maxLCBI4mm assessed by near-infrared spectroscopy (NIRS) after 26 weeks of evolocumab. The secondary endpoints are the changes in (1) the maximal lipid arc, lipid length, lipid volume index, macrophage accumulation and calcification by OCT; (2) PAV and TAV defined by intravascular ultrasound (IVUS) and (3) Changes in PBMC gene expression.

Detailed description: The single center single arm study will be performed in the Cardiac Catheterization laboratory of the Mount Sinai Hospital, New York, NY. After informed consent, patients undergoing clinically indicated elective PCI with a non-obstructive lesion and optimal background statin therapy will be eligible screening. Non-obstructive lesions (30-50% stenosis) identified by angiography in a non-culprit vessel with lipid-rich plaque will be studied. Subjects will receive evolocumab (Repatha) 140 mg subcutaneously every 2 weeks for 26 weeks. Serial NIRS/IVUS and OCT imaging will be performed in the non-obstructive lesions, first during PCI and subsequently after 26 weeks. A total of 25ml of blood will be drawn from the sheath during angiography for transcriptomic profiling of PBMC.

Eligibility criteria: Inclusion criteria:

* Men or women aged 18 years or older at screening who signed written Informed Consent
* Patients with coronary artery disease undergoing cardiac catheterization and PCI for a target lesion and also have a non-obstructive lesion (30-50% stenosis) identified by angiography
* Patients who are not candidates for PCI or CABG currently or over the next 12 months, in the opinion of the investigator
* Patients treated with statins for at least 4 weeks with LDL-C level ≥ 80 mg/dL for low- or moderate -intensity statin use and ≥ 60 mg/dL for high-dose statin. Patients with history of statin intolerance and LDL-C ≥ 100 mg/dL.
* Angiographic criteria: 30-50% reduction of lumen diameter in addition to the target lesion accessible by the OCT catheter. The target segment should not have a history of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), and may not be a bypass graft.
* OCT criteria: target segment should have a lipid-rich plaque with lipid arc \>90° and fibrous cap thickness ≤120 µm.
* Women of childbearing potential must agree to be on an acceptable method of birth control/contraceptive

Exclusion criteria:

* Patients who have acute myocardial infarction (Q wave or non-Q wave with CK-MB \> 5 times above the upper normal (31.5 ng/ml) within 72 hours)
* Patients who are in cardiogenic shock
* Patients with left main disease, in-stent restenotic lesions or patients requiring coronary artery bypass graft surgery
* Patients with elevated CK-MB (\>6.3 ng/ml) or Tnl (\>0.5 ng/ml)
* Patients with platelet count \< 100,000 cell/mm3
* Patients who have co-morbidity which reduces life expectancy to one year
* Patients who are currently participating in another investigational drug/device study
* Patients with liver disease
* Patient with creatinine \> 2.0 mg/dL
* Pregnant women and women of childbearing potential who intend to have children during the duration of the trial
* Patients having undergone heart transplantation, or those that may undergo heart transplantation during the study period
* Patients with active autoimmune disease

Primary outcomes:
measure: Change in Minimal Fibrous Cap Thickness (FCT)
timeFrame: Baseline and 26 Weeks
measure: Number of Participants With FCT <65 µm
timeFrame: Baseline and 26 Weeks
measure: Number of Participants With Increased Fibrous Cap
timeFrame: 26 weeks
measure: Change in maxNIRS4mm
timeFrame: Baseline and 26 Weeks
measure: Number of Participants With Decreased maxLCBI4mm
timeFrame: 26 Weeks
Secondary outcomes:
measure: Change in Maximal Lipid Arc
timeFrame: Baseline and 26 Weeks
measure: Change in Lipid Length
timeFrame: Baseline and 26 weeks
measure: Change in Lipid Volume Index (LVI)
timeFrame: Baseline and 26 Weeks
measure: Change in Macrophage Accumulation
timeFrame: Baseline and 26 Weeks
measure: Change in Macrophage Volume Index
timeFrame: Baseline and 26 Weeks
measure: Change in Macrophage Length
timeFrame: Baseline and 26 Weeks
measure: Change in Calcification Accumulation
timeFrame: Baseline and 26 Weeks
measure: Change in Calcium Length
timeFrame: Baseline and 26 Weeks
measure: Change in Percent Atheroma Volume (PAV)
timeFrame: Baseline and 26 weeks
measure: Change in Total Atheroma Volume (TAV)
timeFrame: Baseline and 26 Weeks
measure: Change in PBMC Gene Expression
timeFrame: Baseline and 1 year
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Annapoorna Kini, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Kini AS, Vengrenyuk Y, Shameer K, Maehara A, Purushothaman M, Yoshimura T, Matsumura M, Aquino M, Haider N, Johnson KW, Readhead B, Kidd BA, Feig JE, Krishnan P, Sweeny J, Milind M, Moreno P, Mehran R, Kovacic JC, Baber U, Dudley JT, Narula J, Sharma S. Intracoronary Imaging, Cholesterol Efflux, and Transcriptomes After Intensive Statin Treatment: The YELLOW II Study. J Am Coll Cardiol. 2017 Feb 14;69(6):628-640. doi: 10.1016/j.jacc.2016.10.029. Epub 2016 Oct 29.
citation: Johnson KW, Glicksberg BS, Shameer K, Vengrenyuk Y, Krittanawong C, Russak AJ, Sharma SK, Narula JN, Dudley JT, Kini AS. A transcriptomic model to predict increase in fibrous cap thickness in response to high-dose statin treatment: Validation by serial intracoronary OCT imaging. EBioMedicine. 2019 Jun;44:41-49. doi: 10.1016/j.ebiom.2019.05.007. Epub 2019 May 22.