Effect of Evolocumab on Coronary Plaque Characteristics (YELLOW III)

Annapoorna Kini

Status and phase

Completed

Phase 4

Conditions

Coronary Artery Disease

Treatments

Drug: Evolocumab Injections

Study type

Interventional

Funder types

Other

Identifiers

NCT04710368

GCO 20-2935

Details and patient eligibility

About

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.

Full 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.

Enrollment

137 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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