Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy

NCT01567826 | Completed Phase 4 Results DMC

• 2 other identifiers: GCO 09-1294IF1292822
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Artery Disease

Keywords

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

Outcome Measures

Primary Outcomes (4)

• 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.

  at baseline and at 6-8 weeks after intervention

• 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.

  at baseline and at 6-8 weeks after intervention

• 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.

  at baseline and at 6-8 weeks after intervention

• Change in LCBI, Lesion

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

  at baseline and at 6-8 weeks post intervention

Secondary Outcomes (6)

• Intravascular Ultrasound (IVUS) Parameters

  at baseline and at 6-8 weeks after intervention

• Fractional Flow Reserve (FFR) Value

  at baseline and at 6-8 weeks after intervention

• Diameter Stenosis

  Baseline and 6-8 weeks post intervention

• Post PCI Cardiac Enzymes

  at 6-8 weeks after intervention

• Major Adverse Cardiac Events (MACE)

  at 6-8 weeks after intervention

Study Arms (2)

standard of care lipid therapy

ACTIVE COMPARATOR

standard-care lipid-lowering therapy: Zocor or Lipitor

Drug: standard of care lipid therapy

aggressive lipid therapy

EXPERIMENTAL

aggressive lipid therapy: Crestor

Drug: Aggressive lipid therapy

Interventions

standard of care lipid therapy DRUG

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 \[less than 40mg\]

Also known as: Zocor, Lipitor, (Zocor, Lipitor, Crestor)

standard of care lipid therapy

Aggressive lipid therapy DRUG

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

Also known as: Rosuvastatin, Crestor

aggressive lipid therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Annapoorna Kini: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (2)

• 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.

  PMID: 23644090 RESULT

• 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.

  PMID: 25190072 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Simvastatin; Atorvastatin; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Sulfur Compounds; Pyrimidines

Limitations and Caveats

Limitations - small sample size and short duration of follow-up.

Results Point of Contact

• Title: Dr. Pedro R. Moreno
• Organization: Icahn School of Medicine at Mount Sinai

pedro.moreno@mountsinai.org

Study Officials

• Annapoorna Kini, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 28, 2012
• First Posted: March 30, 2012
• Study Start: May 1, 2010
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: May 19, 2017
• Results First Posted: February 27, 2017

Record last verified: 2017-04

Locations

US (1)