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Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy (YELLOW)

Primary Purpose

Coronary Artery Disease

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

standard of care lipid therapy

Aggressive lipid therapy

About this trial

This is an interventional treatment trial for Coronary Artery Disease focused on measuring YELLO, Atorvastatin, Simvastatin, Rosuvastatin, lipid therapy, Statin therapy, Coronary artery disease, CHD

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patient > 18 years of age and willing to participate
Stable patients who will undergo cardiac catheterization and PCI (intent to stent)
Patient is willing to go on a cholesterol lowering medication for the duration of the study and willing to change statin therapy to the randomized statin therapy regardless of previous statin therapy and dose (e.g. Atorvastatin 80 mg) Patients that are screened for this study and are receiving another Statin such as Pravachol will be required to be willing to change their therapy to Rosuvastatin as per is randomization. If patients are receiving another statin, such as pravachol, or any other agent, and are at appropriate Lipid levels, they will be permitted to continue this therapy (if randomized to the standard therapy arm). There are a virtually unlimited number of possible scenarios for potential combination of all Lipid lowering agents at the time of enrollment that patients may be taking.
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; or abstinence (no sexual activity).
Fluency in English and/or Spanish

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 or restenotic lesions
Patients with elevated CK-MB (> 6.5 ng/ml) or Tnl (> 0.5ng/L) at baseline
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 known hypersensitivity to HMG CO-A reductase therapy (statins)
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

Sites / Locations

Icahn School of Medicine at Mount Sinai

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

standard of care lipid therapy

aggressive lipid therapy

Arm Description

standard-care lipid-lowering therapy: Zocor or Lipitor

aggressive lipid therapy: Crestor

Outcomes

Primary Outcome Measures

Lipiscan - Lipid Core Burden Index (LCBI)

The regression of yellow plaque content from the atherosclerotic lipid pool after statin therapy by utilizing NIR spectroscopy as compared from baseline to 6-8 weeks after intervention. Spectroscopic information obtained from raw spectra was transformed into a probability of lipid core that was mapped to a red-to-yellow color scale, with the low probability of lipid shown as red and the high probability of lipid shown as yellow. Analyses were performed offline using the Matlab-based software, as previously published. Yellow pixels within the analyzed segment were divided by all viable pixels to generate the lipid-core burden index (LCBI). The maximal value of LCBI for each nonculprit obstructive lesion was recorded and used for comparison.

LCBI4mm Max

LCBI4mm max = change in lipid-core burden index at the 4-mm maximal segment. Spectroscopic information obtained from raw spectra was transformed into a probability of lipid core that was mapped to a red-to-yellow color scale, with the low probability of lipid shown as red and the high probability of lipid shown as yellow. Yellow pixels within the analyzed segment were divided by all viable pixels to generate the lipid-core burden index (LCBI). The maximal value of LCBI for each nonculprit obstructive lesion was recorded and used for comparison.

Change in LCBI4mm Max

Change in LCBI4mm max at 6-8 weeks after intervention as compared to baseline. LCBI4mm max = change in lipid-core burden index at the 4-mm maximal segment.

Change in LCBI, Lesion

Change in LCBI at 6-8 weeks after intervention as compared to baseline

Secondary Outcome Measures

Intravascular Ultrasound (IVUS) Parameters

Change in atheroma volume and lumen CSA on IVUS as related to change in yellow plaque index as compared from baseline to 6-8 weeks after intervention. Data not analyzed. Data not available.

Fractional Flow Reserve (FFR) Value

Change in FFR as related to change in yellow plaque index as compared from baseline to 6-8 weeks after intervention. Fractional flow reserve (FFR), defined as the ratio of maximum flow in the presence of a stenosis to normal maximum flow, is a lesion-specific index of stenosis severity that can be calculated by simultaneous measurement of mean arterial, distal coronary, and central venous pressure.

Diameter Stenosis

Percentage stenosis of vessel diameter in the analysis segment of nontarget lesions as measured by angiography that remained >70%, after successful PCI of the target lesion.

Post PCI Cardiac Enzymes

Correlation of yellow plaque index with post procedure CK-MB, Troponin-I release.

Major Adverse Cardiac Events (MACE)

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 and 1 year. Details reported in adverse events section.

Blood Chemistry - HsCRP

Correlation of yellow plaque index with changes in levels of blood HsCRP as compared from baseline to 6-8 weeks after intervention

Full Information

NCT ID

NCT01567826

First Posted

March 28, 2012

Last Updated

April 11, 2017

Sponsor

Annapoorna Kini

1. Study Identification

Unique Protocol Identification Number

NCT01567826

Brief Title

Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy

Acronym

YELLOW

Official Title

Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy. (YELLOW Trial)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Completed

Study Start Date

May 2010 (undefined)

Primary Completion Date

February 2012 (Actual)

Study Completion Date

February 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Annapoorna Kini

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The study will assess the regression of yellow plaque content of the lipid pool after aggressive lipid therapy by utilizing NIR spectroscopy. Statin therapy using Rosuvastatin 10-40 mg will be compared to the statin therapy of either Atorvastatin or Simvastatin. This is a single site study. A total of 100 subjects will randomized, of which 40 will receive intensive lipid therapy (Rosuvastatin 40mg) and 40 will receive standard care lipid lowering therapy.

Detailed Description

Coronary artery disease (CHD) remains to be a leading cause of death in most countries (1) (2). It is well known that reducing cholesterol level by statin therapy is associated with significant reduction in plaque burden. REVERSAL (3) and ASTEROID (4) trials showed that in patients with coronary artery disease lipid-lowering with atorvastatin or rosuvastatin respectively reduced progression of coronary atherosclerosis and even cause repression of some lesions. CHD clinical events are related to plaque instability due to lipid content within the atherosclerotic plaque. High dose atorvastatin has shown to reduce the plaque lipid contents on serial IVUS analysis at 12 months. Therefore reduction in lipid content and thereby the plaque burden by lipid lowering therapy may stabilize the plaque and reduce cardiovascular events. High sensitivity C-reactive Protein (HsCRP) is an inflammatory biomarker that independently predicts future vascular events. In JUPITER (5) trial rosuvastatin (Crestor) significantly reduced the incidence of major cardiovascular events in apparently healthy people with elevated HsCRP. IVUS was utilized to demonstrate change in coronary artery vessel wall morphology over a relatively short period of time, but provided no data on the lipid content in the vessel wall. The application of NIR spectroscopy to identify lipid deposition within coronary arteries has been validated in ex vivo studies. Infrared spectra are collected as follows: Light of discrete wavelengths from a laser is directed onto the tissue sample via glass fibers. Light scattered from the samples is collected in fibers and launched into a spectrometer. The plot of signal intensity as a function of wavelength was used to develop chemometric models to discriminate lipid-cores from non-atherosclerotic tissue, and from atherosclerotic tissue that is predominantly fibrotic and from blood elements.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Coronary Artery Disease

Keywords

YELLO, Atorvastatin, Simvastatin, Rosuvastatin, lipid therapy, Statin therapy, Coronary artery disease, CHD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

Investigator

Allocation

Randomized

Enrollment

87 (Actual)

8. Arms, Groups, and Interventions

Arm Title

standard of care lipid therapy

Arm Type

Active Comparator

Arm Description

standard-care lipid-lowering therapy: Zocor or Lipitor

Arm Title

aggressive lipid therapy

Arm Type

Experimental

Arm Description

aggressive lipid therapy: Crestor

Intervention Type

Drug

Intervention Name(s)

standard of care lipid therapy

Other Intervention Name(s)

Zocor, Lipitor, (Zocor, Lipitor, Crestor)

Intervention Description

Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy. Zocor, Lipitor [any dose] and Crestor [less than 40mg]

Intervention Type

Drug

Intervention Name(s)

Aggressive lipid therapy

Other Intervention Name(s)

Rosuvastatin, Crestor

Intervention Description

Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy.

Primary Outcome Measure Information:

Title

Lipiscan - Lipid Core Burden Index (LCBI)

Description

Time Frame

at baseline and at 6-8 weeks after intervention

Title

LCBI4mm Max

Description

Time Frame

at baseline and at 6-8 weeks after intervention

Title

Change in LCBI4mm Max

Description

Change in LCBI4mm max at 6-8 weeks after intervention as compared to baseline. LCBI4mm max = change in lipid-core burden index at the 4-mm maximal segment.

Time Frame

at baseline and at 6-8 weeks after intervention

Title

Change in LCBI, Lesion

Description

Change in LCBI at 6-8 weeks after intervention as compared to baseline

Time Frame

at baseline and at 6-8 weeks post intervention

Secondary Outcome Measure Information:

Title

Intravascular Ultrasound (IVUS) Parameters

Description

Change in atheroma volume and lumen CSA on IVUS as related to change in yellow plaque index as compared from baseline to 6-8 weeks after intervention. Data not analyzed. Data not available.

Time Frame

at baseline and at 6-8 weeks after intervention

Title

Fractional Flow Reserve (FFR) Value

Description

Time Frame

at baseline and at 6-8 weeks after intervention

Title

Diameter Stenosis

Description

Percentage stenosis of vessel diameter in the analysis segment of nontarget lesions as measured by angiography that remained >70%, after successful PCI of the target lesion.

Time Frame

Baseline and 6-8 weeks post intervention

Title

Post PCI Cardiac Enzymes

Description

Correlation of yellow plaque index with post procedure CK-MB, Troponin-I release.

Time Frame

at 6-8 weeks after intervention

Title

Major Adverse Cardiac Events (MACE)

Description

Time Frame

at 6-8 weeks after intervention

Title

Blood Chemistry - HsCRP

Description

Correlation of yellow plaque index with changes in levels of blood HsCRP as compared from baseline to 6-8 weeks after intervention

Time Frame

at baseline and at 6-8 weeks after intervention

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patient > 18 years of age and willing to participate Stable patients who will undergo cardiac catheterization and PCI (intent to stent) Patient is willing to go on a cholesterol lowering medication for the duration of the study and willing to change statin therapy to the randomized statin therapy regardless of previous statin therapy and dose (e.g. Atorvastatin 80 mg) Patients that are screened for this study and are receiving another Statin such as Pravachol will be required to be willing to change their therapy to Rosuvastatin as per is randomization. If patients are receiving another statin, such as pravachol, or any other agent, and are at appropriate Lipid levels, they will be permitted to continue this therapy (if randomized to the standard therapy arm). There are a virtually unlimited number of possible scenarios for potential combination of all Lipid lowering agents at the time of enrollment that patients may be taking. 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; or abstinence (no sexual activity). Fluency in English and/or Spanish 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 or restenotic lesions Patients with elevated CK-MB (> 6.5 ng/ml) or Tnl (> 0.5ng/L) at baseline 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 known hypersensitivity to HMG CO-A reductase therapy (statins) 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Annapoorna Kini, MD

Organizational Affiliation

Icahn School of Medicine at Mount Sinai

Official's Role

Principal Investigator

Facility Information:

Facility Name

Icahn School of Medicine at Mount Sinai

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

23644090

Citation

Kini AS, Baber U, Kovacic JC, Limaye A, Ali ZA, Sweeny J, Maehara A, Mehran R, Dangas G, Mintz GS, Fuster V, Narula J, Sharma SK, Moreno PR. Changes in plaque lipid content after short-term intensive versus standard statin therapy: the YELLOW trial (reduction in yellow plaque by aggressive lipid-lowering therapy). J Am Coll Cardiol. 2013 Jul 2;62(1):21-9. doi: 10.1016/j.jacc.2013.03.058. Epub 2013 May 1.

Results Reference

result

PubMed Identifier

25190072

Citation

Dohi T, Maehara A, Moreno PR, Baber U, Kovacic JC, Limaye AM, Ali ZA, Sweeny JM, Mehran R, Dangas GD, Xu K, Sharma SK, Mintz GS, Kini AS. The relationship among extent of lipid-rich plaque, lesion characteristics, and plaque progression/regression in patients with coronary artery disease: a serial near-infrared spectroscopy and intravascular ultrasound study. Eur Heart J Cardiovasc Imaging. 2015 Jan;16(1):81-7. doi: 10.1093/ehjci/jeu169. Epub 2014 Sep 4.

Results Reference

derived

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Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy

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