Effect of Evolocumab on Coronary Plaque Characteristics
- Registration Number
- NCT04710368
- Lead Sponsor
- Annapoorna Kini
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 137
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment Evolocumab Injections Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
- Primary Outcome Measures
Name Time Method Number of Participants With FCT <65 µm Baseline and 26 Weeks Change in Minimal Fibrous Cap Thickness (FCT) Baseline and 26 Weeks Changes in the minimal Minimal Fibrous Cap Thickness (FCT) is assessed by Optical Coherence Tomography (OCT) imaging and measured in microns. FCT describes plaque morphology composition.
Number of Participants With Increased Fibrous Cap 26 weeks Change in maxNIRS4mm Baseline and 26 Weeks Changes in maximal lipid-core burden index within 4 mm (maxLCBI4mm). LCBI4mm is assessed by NIRS and calculated as the fraction of yellow pixels on a chemogram multiplied by 1000. Each pixel on the chemogram represents a probability of lipid presence in the given region; pixels are color-coded on a red-to-yellow color scale, with the low probability of lipid shown as red and the high probability of lipid shown as yellow. Maximal lipid-core burden index is calculated as a fraction of yellow pixels (representing lipid) obtained from the NIRS chemogram multiplied by 1000. It ranges is from 0 to 1000 and represents the amount of lipid in the investigated segment with "0" corresponding to no lipid and "1000" representing all lipid lesion.
Number of Participants With Decreased maxLCBI4mm 26 Weeks
- Secondary Outcome Measures
Name Time Method Change in Maximal Lipid Arc Baseline and 26 Weeks Change in Maximal lipid arc assessed by OCT and measured in degrees.
Change in Lipid Length Baseline and 26 weeks Change in Lipid length by OCT, measured in millimeters.
Change in Lipid Volume Index (LVI) Baseline and 26 Weeks Change in Lipid Volume Length (LVI) calculated as the average lipid arc multiplied by lipid length assessed by OCT.
Change in Macrophage Volume Index Baseline and 26 Weeks Change in the Macrophage Volume Index by OCT, a marker of inflammation (expressed as frequency of the presence of macrophages in lesions.)
Change in Macrophage Accumulation Baseline and 26 Weeks Change in the prevalence of Macrophage accumulation (maximum and average) by OCT, a marker of inflammation (expressed as frequency of the presence of macrophages in lesions.)
Change in Percent Atheroma Volume (PAV) Baseline and 26 weeks Change in PAV assessed by Intravascular Ultrasound (IVUS). PAV characterizes coronary plaque burden and calculated as the proportion of total vessel wall volume occupied by atherosclerotic plaque. The percent atheroma volume is calculated as the proportion of total vessel wall volume occupied by atherosclerotic plaque - plaque volume divided by vessel volume and multiplied by 100.
Change in PBMC Gene Expression Baseline and 1 year Change in PBMC gene expression. Messenger RNA sequencing data will be processed using statistical and bioinformatics analyses.
Change in Macrophage Length Baseline and 26 Weeks Change in Total Atheroma Volume (TAV) Baseline and 26 Weeks Change in TAV assessed by IVUS. TAV characterizes the total volume of coronary plaque.
Change in Calcification Accumulation Baseline and 26 Weeks Change in Calcification accumulation by OCT expressed as frequency of the presence of calcification in lesions.
Change in Calcium Length Baseline and 26 Weeks
Trial Locations
- Locations (1)
Mount Sinai Hospital
🇺🇸New York, New York, United States