The Effect of Rosuvastatin and Olmesartan on the Progression of Coronary Atherosclerotic Disease

The Effect of Rosuvastatin and Olmesartan on the Progression of Coronary Atherosclerotic Disease by Smart Angioplasty Research Team: SMART-ROAD Trial

1. Stains have demonstrated consistent benefits to reduce cardiovascular events in several primary and secondary prevention trials. The suppression of plaque progression or regression may be a part of mechanism of clinical benefit. The intravascular ultrasound studies demonstrated that intensive statin therapy can regress or inhibit the progression of coronary atherosclerosis.
2. Unregulated renin-angiotensin system is important in the pathogenesis of cardiovascular disease. Angiotensin receptor antagonists (ARB) have been reported to improve clinical outcomes in patients with heart failure, left ventricular dysfunction, myocardial infarction, and high-risk patients. Several small studies showed that ARBs were effective to inhibit the progression of coronary atherosclerosis by intravascular ultrasound examination.
3. The combined therapy with statins and ARBs may be additive or synergistic effects on the atherosclerosis regression as well as to improve endothelial dysfunction and insulin resistance in addition to lowering cholesterol levels and blood pressure when compared with either monotherapy in patients.
4. Serial computed tomography angiography (CTA) can be utilized to assess the effect of treatment on coronary plaque morphology. In addition to the assessment of luminal stenosis, CTA also allows characterization of plaque morphology.

Study Overview

• Status: Unknown
• Conditions: Coronary Syndrome
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Placebo of Olmesartan; Drug: Placebo of Rosuvastatin/Olmesartan(Combination); Drug: Olmesartan; Drug: Placebo of Rosuvastatin; Drug: Combination

• Study Type: Interventional
• Enrollment (Anticipated): 504
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hyeon-Cheol Gwon, PhD; Phone Number: 82 2-3410-3418; Email: hcqwon@skku.edu
• Study Contact Backup: Name: Young Bin Song, PhD; Phone Number: 82 2-3410-3419; Email: yoingbin.song@gmail.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Cardiac and Vascular Center; Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must be at 19 years~70 years of age
2. Patients undergoing coronary CTA with coronary artery stenosis 30~70%
3. Informed consent
4. Appropriate CT resolution enough to measure of plaque volume
5. Patients who are stain and renin-angiotensin system blocker naïve at least for 1 year

Exclusion Criteria:

1. Patients with>=70% luminal stenosis or requiring percutaneous coronary intervention(PCI)
2. Severely calcifiedcoronary artery
3. Patients who have a history of previous PCI or coronary artery bypass grafting surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rosuvastatin Arm; Rosuvastatin 10mg in combination with placebo of Olmesartan 20mg plus placebo of Olmesartan/Rosuvastatin(Combination) 20/10mg orally once daily	Drug: Rosuvastatin; Drug: Placebo of Olmesartan; Drug: Placebo of Rosuvastatin/Olmesartan(Combination)
Experimental: Olmesartan Arm; Olmesartan 20mg in combination with placebo of Rosuvastatin 10mg plus placebo of Olmesartan/Rosuvastatin(Combination) 20/10mg orally once daily	Drug: Placebo of Rosuvastatin/Olmesartan(Combination); Drug: Olmesartan; Drug: Placebo of Rosuvastatin
Experimental: Combination Arm; Olmesartan/Rosuvastatin(Combination) 20/10mg in combination with placebo of Rosuvastatin 10mg plus placebo of Olmesartan 20mg	Drug: Placebo of Olmesartan; Drug: Placebo of Rosuvastatin; Drug: Combination; Rosuvastatin/Olmesartan(Combination)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PAV(nominal change of percent atheroma volume) in the proximal to mid segments of major epicardial coronary arteries	Left main, LAD proximal to mid (from ostium to a large second diagonal branch), LCX proximal (from ostium to a large first obtuse marginal branch), RCA (from ostium to a distal bifurcation)	Over the 48weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TAV (nominal change of total atheroma volume) in the proximal to mid segments of major epicardial coronary arteries	Left main, LAD proximal to mid (from ostium to a large second diagonal branch), LCX proximal (from ostium to a large first obtuse marginal branch), RCA (from ostium to a distal bifurcation)	Over the 48weeks
LAPV (nominal change of percent low attenuation plaque volume)		Over the 48weeks
Nominal change of atheroma volume in 10 mm subsegment with greatest disease severity		Over the 48weeks
Change in insulin resistance		Over the 48weeks
Major adverse cardiac events		Over the 48weeks

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Hyeon-Cheol Gwon, PhD, Samsung Medical Center,Seoul,Korea

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Anticipated): August 1, 2018
• Study Completion (Anticipated): August 1, 2018

Study Registration Dates

• First Submitted: August 4, 2015
• First Submitted That Met QC Criteria: August 4, 2015
• First Posted (Estimate): August 6, 2015

Study Record Updates

• Last Update Posted (Estimate): August 6, 2015
• Last Update Submitted That Met QC Criteria: August 4, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Rosuvastatin Calcium; Olmesartan; Olmesartan Medoxomil
• Other Study ID Numbers: 2015-01-055