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Effect of Evolocumab on Coronary Plaque Characteristics (YELLOW III)

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ClinicalTrials.gov Identifier: NCT04710368
Recruitment Status : Not yet recruiting
First Posted : January 14, 2021
Last Update Posted : January 14, 2021
Sponsor:
Information provided by (Responsible Party):
Annapoorna Kini, Icahn School of Medicine at Mount Sinai

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.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Drug: Evolocumab Injections Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: N/A
Intervention Model: Single Group Assignment
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.
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Effect of Evolocumab on Coronary Plaque Characteristics: a Multimodality Imaging Study
Estimated Study Start Date : February 2021
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Evolocumab

Arm Intervention/treatment
Experimental: Treatment
Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks
Drug: Evolocumab Injections
Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
Other Name: Repatha




Primary Outcome Measures :
  1. Change in Minimal Fibrous Cap Thickness (FCT) [ Time Frame: 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

  2. Change in maxNIRS4mm [ Time Frame: Baseline and 26 Weeks ]
    Changes in 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.


Secondary Outcome Measures :
  1. Change in Maximal Lipid Arc [ Time Frame: Baseline and 26 Weeks ]
    Change in Maximal lipid arc assessed by OCT and measured in degrees.

  2. Change in Lipid Length [ Time Frame: Baseline and 26 weeks ]
    Change in Lipid length by OCT, measured in millimeters.

  3. Change in Lipid Volume Index (LVI) [ Time Frame: Baseline and 26 Weeks ]
    Change in Lipid Volume Length (LVI) calculated as the average lipid arc multiplied by lipid length assessed by OCT.

  4. Change in Macrophage Accumulation [ Time Frame: Baseline and 26 Weeks ]
    Change in the prevalence of Macrophage accumulation by OCT, a marker of inflammation (expressed as frequency of the presence of macrophages in lesions.)

  5. Change in Calcification accumulation [ Time Frame: Baseline and 26 Weeks ]
    Change in Calcification accumulation by OCT expressed as frequency of the presence of calcification in lesions.

  6. Change in Percent Atheroma Volume (PAV) [ Time Frame: 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.

  7. Change in Total Atheroma Volume (TAV) [ Time Frame: Baseline and 26 Weeks ]
    Change in TAV assessed by IVUS. TAV characterizes the total volume of coronary plaque.

  8. Change in PBMC Gene Expression [ Time Frame: Baseline and 26 Weeks ]
    Change in PBMC gene expression. Messenger RNA sequencing data will be processed using statistical and bioinformatics analyses.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04710368


Contacts
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Contact: Annapoorna Kini, MD (212) 241-4181 annapoorna.kini@mountsinai.org
Contact: Yuliya Vengrenyuk, PhD (212) 241-0460 yuliya.vengrenyuk@mountsinai.org

Locations
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United States, New York
Mount Sinai Hospital
New York, New York, United States, 10029
Contact: Yuliya Vengrenyuk, PhD       yuliya.vengrenyuk@mountsinai.org   
Principal Investigator: Annapoorna Kini, MD         
Sponsors and Collaborators
Annapoorna Kini
Investigators
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Principal Investigator: Annapoorna Kini, MD Icahn School of Medicine at Mount Sinai
Publications:

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Responsible Party: Annapoorna Kini, Professor of Medicine, Cardiology, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT04710368    
Other Study ID Numbers: GCO 20-2935
First Posted: January 14, 2021    Key Record Dates
Last Update Posted: January 14, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Annapoorna Kini, Icahn School of Medicine at Mount Sinai:
Coronary Artery Disease
Coronary Plaque
Optical Coherence Tomography
Near-Infrared Spectroscopy
Evolocumab
Statin
Additional relevant MeSH terms:
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Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Evolocumab
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents