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YELLOW II Study: Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Mount Sinai School of Medicine
Sponsor:
Collaborators:
Texas Heart Institute (Wafic Said Molecular Cardiology Research Lab)
Astrazeneca (direct)
InfraReDx (indirect)
Information provided by (Responsible Party):
Annapoorna Kini, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01837823
First received: April 5, 2013
Last updated: October 21, 2014
Last verified: October 2014
  Purpose

Coronary artery disease (CAD) remains a leading cause of death in most countries. It is well known that the reduction of cholesterol levels by statin therapy is associated with significant decreases in plaque burden. REVERSAL, ASTEROID, and more recently the SATURN II trial showed that in patients with CAD, lipid lowering with atorvastatin or rosuvastatin respectively reduced progression of coronary atherosclerosis, even causing plaque regression of some lesions. CAD clinical events are related to plaque instability due to lipid content and activity within the atherosclerotic plaque. The investigators recently completed the YELLOW I study, and identified that intensive statin therapy (rosuvastatin 40mg) was associated with a reduction in the amount of lipid in obstructive coronary plaques, as measured by near-infrared spectroscopy (NIRS). The YELLOW II study is designed to expand and build upon these results, and to provide mechanistic insights into the potential benefits of intensive statin therapy on atherosclerotic plaques.


Condition Intervention Phase
Obstructive Coronary Artery Disease
Coronary Artery Disease
Drug: rosuvastatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: YELLOW II Study: Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Change in maximal 4mm lipid core burden index (LCBI 4mm max) [ Time Frame: baseline and at 8-12 weeks ] [ Designated as safety issue: No ]
    Change in maximum LCBI 4mm (ΔLCBI4mm max) of the non-culprit YELLOW lesion from baseline to 8-12 weeks thereafter


Secondary Outcome Measures:
  • Change in OCT and IVUS imaging measures [ Time Frame: baseline and at 8-12 weeks ] [ Designated as safety issue: No ]
    ΔLCBI4mm max will be related to Δ values from baseline to 8-12 weeks thereafter in specific OCT and IVUS imaging measures.

  • Change in inflammatory and lipid parameters [ Time Frame: baseline and at 8-12 weeks ] [ Designated as safety issue: No ]
    ΔLCBI4mm max will be related to Δ values from baseline to 8-12 weeks thereafter in inflammatory and lipid parameters, including haptoglobin, LDL, HDL, LDL charge defined subfractions, and macrophage responses to patient-derived samples.

  • Change in lesion LCBI [ Time Frame: at baseline and at 8-12 weeks ] [ Designated as safety issue: No ]
    As related to other outcomes, change in LCBI measured across the entire lesion (rather than ΔLCBI4mm max).

  • Change in LCBI 4mm at same anatomical site [ Time Frame: at baseline and at 8-12 weeks ] [ Designated as safety issue: No ]
    As related to other outcomes, change in LCBI 4mm measured at the identical anatomical site at both time points, as defined by the LCBI4mm max site at baseline (rather than ΔLCBI4mm max).

  • Change in atheroma morphology and characteristics [ Time Frame: baseline and at 8-12 weeks ] [ Designated as safety issue: No ]
    Change in atheroma volume and lumen cross sectional area on OCT as related to ΔLCBI4mm max.

  • Biomarker release [ Time Frame: within 24 hrs of PCI ] [ Designated as safety issue: No ]
    Correlation of LCBI4mm max and other OCT and IVUS parameters with post procedure CK-MB, Troponin-I release at final YELLOW lesion PCI.

  • Correlation of baseline lipid parameters with baseline LCBI4mm max [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Correlation of baseline lipid parameters with baseline LCBI4mm max

  • change in plaque morphology as related to haptoglobin [ Time Frame: baseline and at 8-12 weeks ] [ Designated as safety issue: No ]
    To relate changes in plaque lipid content and morphology to the patient haptoglobin genotype.

  • change in mechanism of reverse cholesterol transport [ Time Frame: baseline and at 8-12 weeks ] [ Designated as safety issue: No ]
    To assess the mechanism of reverse cholesterol transport that arises with high-dose statin therapy, as related to changes in plaque lipid content and morphology, and systemic vascular inflammation.

  • MACE [ Time Frame: at 30 days ] [ Designated as safety issue: Yes ]
    Major Adverse Cardiac Events (MACE) defined as a combined clinical endpoint of death, MI (Q wave or non Q-wave with CK-MB >3 times above the upper normal limit (48 U/L), urgent revascularization or stroke at 30 days.

  • MACE [ Time Frame: at 1 year ] [ Designated as safety issue: Yes ]
    Major Adverse Cardiac Events (MACE) defined as a combined clinical endpoint of death, MI (Q wave or non Q-wave with CK-MB >3 times above the upper normal limit (48 U/L), urgent revascularization or stroke at 1 year.


Estimated Enrollment: 80
Study Start Date: July 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rosuvastatin
All subjects will receive rosuvastatin 40mg/day
Drug: rosuvastatin
All subjects will receive rosuvastatin 40mg/day for 8-12 weeks
Other Name: Crestor

Detailed Description:

YELLOW II is a single site study and will assess the regression of plaque lipid content and changes in plaque morphology from atherosclerotic lesions after high-dose statin therapy by utilizing NIRS, IVUS and optical coherency tomography (OCT) imaging modalities in the coronary arteries. We propose to image non-culprit coronary lesions using these modalities in patients with two or three diseased coronary vessels deemed to warrant intervention on clinical grounds. Thus, at the time of enrolment patients will undergo Percutaneous Coronary Intervention (PCI) of a non-study culprit lesion, and triple-modality imaging of the potential non-culprit ('YELLOW') lesion. If there is high baseline lipid content in the non-culprit YELLOW lesion (max 4mm LCBI > 150), patients will be formally entered into this study. Following this, all enrolled subjects will receive high-dose lipid lowering therapy (rosuvastatin 40mg daily). The non-culprit YELLOW lesion will undergo staged intervention 8-12 weeks following study enrolment and baseline imaging. At this time the YELLOW lesion will be reimaged to determine whether high-dose statin therapy caused a reduction in lipid content as assessed by NIRS, and other altered plaque morphology as assessed by OCT and IVUS. In addition, both at baseline and at the time of final non-culprit YELLOW lesion PCI, blood samples will be drawn for the assessment of haptoglobin genotype, LDL, HDL, macrophage profiling in response to certain changes in these lipid moieties and other parameters that may be related to changes in the YELLOW lesion as a result of intensive statin therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients >18 years of age and willing to participate.
  • Fluency in either English or Spanish.
  • Stable patients who will undergo cardiac catheterization and PCI (intent to stent).
  • Patient is willing to go on high-dose cholesterol lowering medication for the duration of the study
  • Signed written Informed Consent.
  • Women of childbearing potential must agree to be on an acceptable method of birth control/contraceptive such as barrier method (condoms/diaphragm); hormonal contraceptives (birth control pills, implants (Norplant) or injections (Depo-Provera)); Intrauterine Device.
  • Proposed non-culprit YELLOW study lesion with max 4mm LCBI ≥ 150.

Exclusion Criteria:

  • Patients who have acute myocardial infarction (ST-segment elevation presentation, new Q waves or non-ST segment elevation with CK-MB > 5 times above the upper normal (31.5 ng/ml) within 72 hours).
  • Patients who are in cardiogenic shock.
  • Patients requiring coronary artery bypass graft surgery.
  • 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.
  • Active autoimmune disease.
  • Nursing mothers
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01837823

Contacts
Contact: Annapoorna Kini, MD 212-241-4181 annapoorna.kini@mountsinai.org
Contact: Jason Kovacic, MD, PhD 212-241-4059 jason.kovacic@mountsinai.org

Locations
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Principal Investigator: Annapoorna Kini, MD         
Principal Investigator: Jason Kovacic, MD, PhD         
Sponsors and Collaborators
Mount Sinai School of Medicine
Texas Heart Institute (Wafic Said Molecular Cardiology Research Lab)
Astrazeneca (direct)
InfraReDx (indirect)
Investigators
Principal Investigator: Annapoorna Kini, MD Mount Sinai School of Medicine
Principal Investigator: Jason Kovacic, MD, PhD Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: Annapoorna Kini, Professor of Medicine, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01837823     History of Changes
Other Study ID Numbers: GCO 12-1507, HS#: 12-00741
Study First Received: April 5, 2013
Last Updated: October 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Mount Sinai School of Medicine:
Coronary artery disease
Lipid
Regression
Plaque

Additional relevant MeSH terms:
Coronary Artery Disease
Coronary Disease
Inflammation
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
Vascular Diseases
Rosuvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014