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| ID | Type | Description | Link |
|---|---|---|---|
| IF1292822 |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| standard of care lipid therapy | Active Comparator | standard-care lipid-lowering therapy: Zocor or Lipitor |
|
| aggressive lipid therapy | Experimental | aggressive lipid therapy: Crestor |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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] |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | at baseline and at 6-8 weeks after intervention |
| Fractional Flow Reserve (FFR) Value |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Annapoorna Kini, MD | Icahn School of Medicine at Mount Sinai | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23644090 | Result | 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. | |
| 25190072 |
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779 patients consecutive patients with chronic stable angina presenting for elective coronary angiography were screened from May 21, 2010 until Jan 10, 2012. 87 participants met criteria and were randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | Standard of Care Lipid Therapy | standard-care lipid-lowering therapy: Zocor or Lipitor 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] |
| FG001 | Aggressive Lipid Therapy | aggressive lipid therapy: Crestor 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Standard of Care Lipid Therapy | standard-care lipid-lowering therapy: Zocor or Lipitor 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] |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Data were not available in 17 patients because of loss to follow-up (n = 5), incorrect image formatting that could not be recovered at the time of core laboratory analysis (n = 5), NIRS console/catheter malfunction at the time of index PCI (n = 3), and loss of disc integrity or corruption before core laboratory analysis (n = 4). | Posted | Median | Inter-Quartile Range | ratio | at baseline and at 6-8 weeks after intervention |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Standard of Care Lipid Therapy | standard-care lipid-lowering therapy: Zocor or Lipitor |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization | Cardiac disorders | Hospitalization for Chest Pain |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Unplanned revascularization | Vascular disorders |
Limitations - small sample size and short duration of follow-up.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Pedro R. Moreno | Icahn School of Medicine at Mount Sinai | pedro.moreno@mountsinai.org |
Not provided
| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D019821 | Simvastatin |
| D000069059 | Atorvastatin |
| D000068718 | Rosuvastatin Calcium |
| ID | Term |
|---|---|
| D008148 | Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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|
| 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. |
|
|
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. |
| at baseline and at 6-8 weeks after intervention |
| 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. | Baseline and 6-8 weeks post intervention |
| Post PCI Cardiac Enzymes | Correlation of yellow plaque index with post procedure CK-MB, Troponin-I release. | at 6-8 weeks after intervention |
| 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. | at 6-8 weeks after intervention |
| 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 | at baseline and at 6-8 weeks after intervention |
| Derived |
| 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. |
| Aggressive Lipid Therapy |
aggressive lipid therapy: Crestor 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Current tobacco use | Number | participants |
|
| Hypertension | Number | participants |
|
| Hypercholesterolemia | Number | participants |
|
| Diabetes mellitus | (treated with insulin) | Number | participants |
|
| Prior CVA/TIA | Cerebrovascular accident (CVA); Transient ischemic attack (TIA) | Number | participants |
|
| Previous MI | Myocardial infarction (MI) | Number | participants |
|
| Previous PCI | Percutaneous coronary intervention (PCI) | Number | participants |
|
| Statin Use | Number | participants |
|
| Beta-blocker use | Number | participants |
|
| ACE-I/ARB use | Angiotensin-converting enzyme inhibitor (ACE-I); Angiotensin receptor blocker (ARB) | Number | participants |
|
| Creatinine | Mean | Standard Deviation | mg/dl |
|
| LAD Coronary vessel | Left anterior descending (LAD) | Number | participants |
|
| LCx coronary vessel | Left circumflex (LCx) | Number | participants |
|
| RCA coronary vessel | Right coronary artery (RCA) | Number | participants |
|
| ID | Title | Description |
|---|
| OG000 | Standard of Care Lipid Therapy | standard-care lipid-lowering therapy: Zocor or Lipitor 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] |
| OG001 | Aggressive Lipid Therapy | aggressive lipid therapy: Crestor 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. |
|
|
| Primary | 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. | Data were not available in 17 patients because of loss to follow-up (n = 5), incorrect image formatting that could not be recovered at the time of core laboratory analysis (n = 5), NIRS console/catheter malfunction at the time of index PCI (n = 3), and loss of disc integrity or corruption before core laboratory analysis (n = 4). | Posted | Median | Inter-Quartile Range | ratio | at baseline and at 6-8 weeks after intervention |
|
|
|
| Primary | 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. | Data were not available in 17 patients because of loss to follow-up (n = 5), incorrect image formatting that could not be recovered at the time of core laboratory analysis (n = 5), NIRS console/catheter malfunction at the time of index PCI (n = 3), and loss of disc integrity or corruption before core laboratory analysis (n = 4). | Posted | Median | 95% Confidence Interval | ratio | at baseline and at 6-8 weeks after intervention |
|
|
|
|
| Primary | Change in LCBI, Lesion | Change in LCBI at 6-8 weeks after intervention as compared to baseline | Data were not available in 17 patients because of loss to follow-up (n = 5), incorrect image formatting that could not be recovered at the time of core laboratory analysis (n = 5), NIRS console/catheter malfunction at the time of index PCI (n = 3), and loss of disc integrity or corruption before core laboratory analysis (n = 4). | Posted | Median | 95% Confidence Interval | ratio | at baseline and at 6-8 weeks post intervention |
|
|
|
|
| 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. Data not analyzed. Data not available. | Posted | Mean | Standard Deviation | mm^2 | at baseline and at 6-8 weeks after intervention |
|
|
|
| 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. 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. | Posted | Mean | Standard Deviation | ratio | at baseline and at 6-8 weeks after intervention |
|
|
|
| Secondary | 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. | Posted | Number | percentage of lesions | Baseline and 6-8 weeks post intervention |
|
|
|
| Secondary | Post PCI Cardiac Enzymes | Correlation of yellow plaque index with post procedure CK-MB, Troponin-I release. | Posted | Mean | Standard Deviation | ng/mL | at 6-8 weeks after intervention |
|
|
|
| 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. Details reported in adverse events section. | Posted | Number | participants | at 6-8 weeks after intervention |
|
|
|
| Secondary | 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 | Posted | Median | Inter-Quartile Range | mg/l | at baseline and at 6-8 weeks after intervention |
|
|
|
| 2 |
| 43 |
| 9 |
| 43 |
| EG001 | Aggressive Lipid Therapy | aggressive lipid therapy: Crestor | 3 | 44 | 7 | 44 |
| Periprocedural complications | Injury, poisoning and procedural complications |
|
| Any bleeding | Blood and lymphatic system disorders |
|
| AST > 3x ULN | Hepatobiliary disorders | aspartate aminotransferase (AST); upper limit of normal (ULN) |
|
| ALT > 3x ULN | Hepatobiliary disorders | alanine aminotransferase (ALT); upper limit of normal (ULN) |
|
| Creatine kinase-MB > 5x ULN | Renal and urinary disorders |
|
| Creatine kinase-MB >10x ULN | Renal and urinary disorders |
|
| Statin discontinuation | General disorders |
|
| Statin dose reduction | General disorders |
|
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| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006538 | Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| Baseline Lumen CSA |
|
| 6-8 weeks Lumen CSA |
|