Statin and Atheroma Vulnerability Evaluation (STABLE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2012 by CardioVascular Research Foundation, Korea
Sponsor:
Collaborator:
CardioVascular Research Foundation, Korea
Information provided by (Responsible Party):
Seung-Jung Park, CardioVascular Research Foundation, Korea
ClinicalTrials.gov Identifier:
NCT00997880
First received: October 18, 2009
Last updated: August 7, 2012
Last verified: August 2012
  Purpose

The purpose of this study is to evaluate the effect of statin therapy on the modification of atherosclerotic plaque composition and vulnerability in non-intervened coronary arteries with mild to moderate stenosis using VH-IVUS and OCT.


Condition Intervention Phase
Coronary Artery Disease
Drug: Rosuvastatin calcium 40mg
Drug: Rosuvastatin calcium10mg
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of High-Dose and Low-Dose Statin for Coronary Plaque Modification

Resource links provided by NLM:


Further study details as provided by CardioVascular Research Foundation, Korea:

Primary Outcome Measures:
  • Percent compositional change of coronary plaque in the entire pullback length Percent compositional c Percent hange of coronary plaque in the entire pullback length of "target segment" (within both proximal and distal fiduciary sites) [ Time Frame: 12months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • VH-IVUS parameters [ Time Frame: 12months ] [ Designated as safety issue: Yes ]
  • Conventional IVUS parameters [ Time Frame: 12months ] [ Designated as safety issue: Yes ]
  • OCT Sub-study parameters [ Time Frame: 12months ] [ Designated as safety issue: Yes ]
  • Serum biomarkers [ Time Frame: 12months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 312
Study Start Date: April 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rosuvastatin calcium 40mg
high-dose (40mg rosuvastatin)
Drug: Rosuvastatin calcium 40mg
Rosuvastatin calcium 40mg
Other Name: CRESTOR® 40mg
Active Comparator: Rosuvastatin calcium10mg
low-dose statin (10mg rosuvastatin)
Drug: Rosuvastatin calcium10mg
Rosuvastatin 10mg
Other Name: CRESTOR® 10mg

Detailed Description:

At present, there is no proven drug or modality to stabilize the vulnerable plaques. A number of drugs that are beneficial for patients with coronary disease may act in part by improving the stability of plaques that are vulnerable for future rupture. Especially, Lipid-lowering therapy, particularly with statins, can stabilize vulnerable plaques or those that have already ruptured by improving endothelial function and reducing thrombogenicity, platelet aggregation, and possibly inflammation. As the atherosclerotic disease has progressed, there is an increase of the atherosclerotic plaque amounts. However, the changes of specific plaque compositions within the atherosclerotic lesions have not been sufficiently evaluated. Previous pathologic findings reported that there was a significant relation between the plaque size and necrotic core size.Conventional grey-scale intravascular ultrasound (IVUS) has significant limitations in accurately assessing atheromatous plaque composition. These limitations have been partially addressed by radiofrequency signal processing with spectral analysis of the back-scattered ultrasound signals. Using this technology, Virtual Histology (VH) IVUS is capable of characterizing plaque as calcified (white), fibrotic (dark-green), fibrofatty (yellow-green), and necrotic core (red). In addition, optical coherence tomography (OCT) is a light-based imaging modality that can be used in biological systems to study tissues in vivo with near-histologic, ultrahigh resolution. The rationale for intravascular application of OCT is its potential for in vivo visualizations of the coronary artery microstructure. This unique image resolution of OCT offers the potential to detect key features of vulnerable plaque in vivo. Beyond the inherent limitations of angioscopy and intravascular ultrasound, OCT might offer a much higher sensitivity in the detection of necrotic/lipid cores within coronary atheromas. Therefore, plaque characterization using VH-IVUS and OCT may provide detailed morphologic insights of plaque vulnerability.

We hypothesized that statin would provide benefits to stabilize coronary plaque composition by LDL-reduction and/or a pleiotropic effect. We also hypothesized that high-dose statin would be more beneficial in reducing the vulnerable plaque and stabilizing the vulnerable plaque composition than low-dose statin.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female at least 18 years of age inclusive.
  2. Patients with stable (CCS class 1 to 4) or acute coronary syndromes (unstable angina pectoris Braunwald class IB, IC, IIB, IIC, IIIB, IIIC or NSTEMI) or patients with atypical chest pain or without symptoms but having documented myocardial ischemia who will undergo either planned coronary angiography, or percutaneous coronary intervention
  3. Non-culprit de novo lesion in a native coronary artery with at least one deferred coronary lesion with 1) visually-estimated angiographic % diameter stenosis 20-50% or 2) % diameter stenosis >50% without any evidence of inducible ischemia (FFR≥0.8 or negative perfusion on thiallium scan or negative treadmill test). Index lesion should have at least 1 fibroatheroma or TCFA.
  4. The patient or guardian agrees to the study protocol and the schedule of clinical and angiographic follow-up, and provides informed, written consent, as approved by the appropriate Institutional Review Board/Ethical Committee of the respective clinical site

Exclusion Criteria:

  1. Planned cardiac surgery (e.g., CABG, valve repair or replacement, or aneurysmectomy) or planned major non-cardiac surgery within the study period
  2. Stroke or resuscitated sudden death in the past 6 months
  3. Chronic disease requiring treatment with oral, intravenous, or intra-articular corticosteroids (use of topical, inhaled, or nasal corticosteroids is permissible)
  4. Untreated hyperthyroidism, or hypothyroidism with TSH levels more than 1.5 times upper limit of normal
  5. A diagnosis of cancer (other than superficial squamous or basal cell skin cancer) in the past 3 years or current treatment for the active cancer
  6. Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the Investigator, would preclude safe completion of the study
  7. Evidence of congestive heart failure, or left ventricular ejection fraction < 40%
  8. Significant renal disease manifested by serum creatinine > 2.0mg/dL, or creatinine clearance of < 40 ml/min (by Cockcroft-Gault method)
  9. Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST > 3 times upper limit of normal)
  10. History of myopathy or elevated creatine kinase (CK) > 3 times upper normal limit at screening
  11. History of adult asthma manifested by bronchospasm in the past 6 months, or currently taking regular anti-asthmatic medication(s)
  12. Unwillingness or inability to comply with the procedures described in this protocol
  13. History of any arterial bypass or angioplastic intervention involving the target vessel
  14. The luminal narrowing in the target vessel or in the left main coronary artery >50% by visual inspection of angiogram
  15. Luminal diameter of the target vessel < 2.5mm by visual inspection of coronary angiogram
  16. Presence of thrombus or complex plaque morphology in the target vessel that suggests a high likelihood of distal embolism
  17. Severe tortuosity of the target vessel or any other anatomical reasons that the investigator deems inappropriate for IVUS procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00997880

Contacts
Contact: Seung-Jung Park, MD,PhD (82-2)-3010-4812 sjpark@amc.seoul.kr
Contact: Duk-Woo Park, MD,PhD (82-2)-3010-3995 dwpark@amc.seoul.kr

Locations
Korea, Republic of
Asan Medical Center Recruiting
Seoul, Republic of Korea, Korea, Republic of, 138-736
Contact: Seung-Jung Park, MD,PhD    (82-2)-3010-4812    sjpark@amc.seoul.kr   
Contact: Duk-Woo Park, MD,PhD    (82-2)-3010-3995    dwpark@amc.seoul.kr   
Principal Investigator: Seung-Jung Park         
Sponsors and Collaborators
Seung-Jung Park
CardioVascular Research Foundation, Korea
Investigators
Principal Investigator: Seung-Jung Park, MD,PhD Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine
  More Information

No publications provided

Responsible Party: Seung-Jung Park, M.D., Ph.D.,Professor of Medicine Asan Medical Center, University of Ulsan, College of Medicine, CardioVascular Research Foundation, Korea
ClinicalTrials.gov Identifier: NCT00997880     History of Changes
Other Study ID Numbers: 2008-0361
Study First Received: October 18, 2009
Last Updated: August 7, 2012
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by CardioVascular Research Foundation, Korea:
rosuvastatin

Additional relevant MeSH terms:
Calcium, Dietary
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Rosuvastatin
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 23, 2014