Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy

NCT ID: NCT01567826

Last Updated: 2017-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2012-02-29

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.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

standard of care lipid therapy

standard-care lipid-lowering therapy: Zocor or Lipitor

Group Type: ACTIVE_COMPARATOR

standard of care lipid therapy

Intervention Type: 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]

aggressive lipid therapy

aggressive lipid therapy: Crestor

Group Type: EXPERIMENTAL

Aggressive lipid therapy

Intervention Type: 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.

Interventions

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]

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Zocor; Lipitor; (Zocor, Lipitor, Crestor); Rosuvastatin; Crestor

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Annapoorna Kini

OTHER

Sponsor Role: lead

Responsible Party

Annapoorna Kini

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Annapoorna Kini, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 23644090 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25190072 (View on PubMed)

Other Identifiers

IF1292822

Identifier Type: -

Identifier Source: secondary_id

GCO 09-1294

Identifier Type: -

Identifier Source: org_study_id