Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy

Coronary Artery Disease Clinical Trial

— YELLOW  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01567826
• Other study ID #: GCO 09-1294
• Secondary ID: IF1292822
• Status: Completed
• Phase: Phase 4
• First received: March 28, 2012
• Last updated: February 10, 2015
• Start date: May 2010
• Est. completion date: February 2012

Study information

• Verified date: February 2015
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 87
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

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

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Annapoorna Kini

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lipiscan - Lipid core burden (LCBI)	The study will assess 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.	at baseline and at 6-8 weeks after intervention	No
Secondary	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.	at baseline and at 6-8 weeks after intervention	No
Secondary	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.	at baseline and at 6-8 weeks after intervention	No
Secondary	post PCI cardiac enzymes	Correlation of yellow plaque index with post procedure CK-MB, Troponin-I release.	at 6-8 weeks after intervention	No
Secondary	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.	at 6-8 weeks after intervention	No
Secondary	blood chemistry - HsCRP	Correlation of yellow plaque index with changes in levels of peripheral blood/serum leukocytes, leukocyte sub-types, HsCRP as compared from baseline to 6-8 weeks after intervention	at baseline and at 6-8 weeks after intervention	No