Clinical trial NCT01567826: Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy
Official title: Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy. (YELLOW Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: YELLO
Atorvastatin
Simvastatin
Rosuvastatin
lipid therapy
Statin therapy
Coronary artery disease
CHD
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2012-03-30
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Lipiscan - Lipid Core Burden Index (LCBI)
timeFrame: at baseline and at 6-8 weeks after intervention
measure: LCBI4mm Max
timeFrame: at baseline and at 6-8 weeks after intervention
measure: Change in LCBI4mm Max
timeFrame: at baseline and at 6-8 weeks after intervention
measure: Change in LCBI, Lesion
timeFrame: at baseline and at 6-8 weeks post intervention
Secondary outcomes:
measure: Intravascular Ultrasound (IVUS) Parameters
timeFrame: at baseline and at 6-8 weeks after intervention
measure: Fractional Flow Reserve (FFR) Value
timeFrame: at baseline and at 6-8 weeks after intervention
measure: Diameter Stenosis
timeFrame: Baseline and 6-8 weeks post intervention
measure: Post PCI Cardiac Enzymes
timeFrame: at 6-8 weeks after intervention
measure: Major Adverse Cardiac Events (MACE)
timeFrame: at 6-8 weeks after intervention
measure: Blood Chemistry - HsCRP
timeFrame: at baseline and at 6-8 weeks after intervention
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Annapoorna Kini, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.