Plaque REgression With Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS)

The purpose of this study was to evaluate the difference in the effect of coronary plaque regression (as measured by intravascular ultrasound [IVUS] imaging) between cholesterol absorption inhibitor and cholesterol synthesis inhibitor.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Hypercholesterolemia
• Intervention / Treatment: Drug: Combination therapy with Lipitor [Atorvastatin] and Zetia [Ezetimibe]; Drug: Lipitor (Atorvastatin) monotherapy

• Study Type: Interventional
• Enrollment (Actual): 245
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Kumamoto, Japan, 8608556
    • Kumamoto University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed written informed consent,
• 30 to 85 years old,
• Plan to undergo PCI and LDL-C >= 100 mg/dL

Exclusion Criteria:

• Familial hypercholesterolemia
• Being treated with Zetia (Ezetimibe)
• Being treated with Fibrates
• Renal insufficiency (serum creatinine >= 2.0 mg/dl)
• Altered hepatic function (serum aspartate aminotransferase or alanine aminotransferase >= 3-folds of standard value in each institute)
• Undergoing hemodialysis or peritoneal dialysis
• Allergic to Lipitor and/or Zetia
• Severe underlying disease
• Lack of decision-making capacity
• Recognized as inadequate by attending doctor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LZ group	Drug: Combination therapy with Lipitor [Atorvastatin] and Zetia [Ezetimibe]; Zetia 10 mg/dl + Lipitor. The dosage of Lipitor will be titrated up to a maximum of 20 mg/day with a treatment goal of lowering LDL-C below 70 mg/dl.
ACTIVE_COMPARATOR: L group	Drug: Lipitor (Atorvastatin) monotherapy; The dosage will be titrated up to a maximum of 20 mg/day, which is the highest approved regimen by the Ministry of Health, Labor and Welfare of Japan, with a treatment goal of lowering LDL-C below 70 mg/dl.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absolute change from baseline to follow-up in percent atheroma volume (PAV) in the target lesion	before randomization & 9-12 months after randomization

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage change from baseline (before randomization) to follow-up (9-12 months after randomization) in the atheroma volume	before randomization & 9-12 months after randomization
Change and percentage change from baseline to follow-up in the minimum lumen diameter (MLD) and percent diameter stenosis (%DS)	before randomization & 9-12 months after randomization
Percentage changes from baseline to follow-up in serum lipids	before randomization & 9-12 months after randomization
Correlation between regression of coronary plaque and serum lipids profiles	before randomization & 9-12 months after randomization
Changes in hs-CRP from baseline to follow-up	before randomization & 9-12 months after randomization
Correlation between regression of coronary plaque and inflammatory markers (white blood cell count and hs-CRP)	before randomization & 9-12 months after randomization
Change and percentage change from baseline to follow-up in the PV of the PCI target lesion	before randomization & 9-12 months after randomization
Change and percentage change from baseline to follow-up in the MLD and %DS of the PCI target lesion	before randomization & 9-12 months after randomization
MACE (cardiac death, non-fatal Q wave and/or non-Q wave myocardial infarction, target vessel revascularization [percutaneous coronary intervention or coronary artery bypass grafting])	before randomization & 9-12 months after randomization
All-cause death	before randomization & 9-12 months after randomization
Safety (Adverse events, subjective symptoms/objective findings, physical tests), blood tests [hematology, clinical chemistry, glucose metabolism test], urinalysis)	before randomization & 9-12 months after randomization

Collaborators and Investigators

• Sponsor: Kumamoto University
• Investigators: Study Chair: Hisao Ogawa, MD, PhD, Kumamoto University, Graduate School of Medical Sciences

Publications and helpful links

General Publications

• Fujisue K, Nagamatsu S, Shimomura H, Yamashita T, Nakao K, Nakamura S, Ishihara M, Matsui K, Yamamoto N, Koide S, Matsumura T, Fujimoto K, Tsunoda R, Morikami Y, Matsuyama K, Oshima S, Sakamoto K, Izumiya Y, Kaikita K, Hokimoto S, Ogawa H, Tsujita K. Impact of statin-ezetimibe combination on coronary atheroma plaque in patients with and without chronic kidney disease - Sub-analysis of PRECISE-IVUS trial. Int J Cardiol. 2018 Oct 1;268:23-26. doi: 10.1016/j.ijcard.2018.04.051. Epub 2018 Jun 18.
• Tsujita K, Yamanaga K, Komura N, Sakamoto K, Sugiyama S, Sumida H, Shimomura H, Yamashita T, Oka H, Nakao K, Nakamura S, Ishihara M, Matsui K, Sakaino N, Nakamura N, Yamamoto N, Koide S, Matsumura T, Fujimoto K, Tsunoda R, Morikami Y, Matsuyama K, Oshima S, Kaikita K, Hokimoto S, Ogawa H; PRECISE-IVUS Investigators. Lipid profile associated with coronary plaque regression in patients with acute coronary syndrome: Subanalysis of PRECISE-IVUS trial. Atherosclerosis. 2016 Aug;251:367-372. doi: 10.1016/j.atherosclerosis.2016.05.025. Epub 2016 May 20.
• Tsujita K, Sugiyama S, Sumida H, Shimomura H, Yamashita T, Yamanaga K, Komura N, Sakamoto K, Oka H, Nakao K, Nakamura S, Ishihara M, Matsui K, Sakaino N, Nakamura N, Yamamoto N, Koide S, Matsumura T, Fujimoto K, Tsunoda R, Morikami Y, Matsuyama K, Oshima S, Kaikita K, Hokimoto S, Ogawa H; PRECISE-IVUS Investigators. Impact of Dual Lipid-Lowering Strategy With Ezetimibe and Atorvastatin on Coronary Plaque Regression in Patients With Percutaneous Coronary Intervention: The Multicenter Randomized Controlled PRECISE-IVUS Trial. J Am Coll Cardiol. 2015 Aug 4;66(5):495-507. doi: 10.1016/j.jacc.2015.05.065.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (ACTUAL): March 1, 2014
• Study Completion (ACTUAL): September 1, 2014

Study Registration Dates

• First Submitted: January 5, 2010
• First Submitted That Met QC Criteria: January 5, 2010
• First Posted (ESTIMATE): January 6, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): April 1, 2015
• Last Update Submitted That Met QC Criteria: March 30, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Cardiovascular Diseases; Coronary Artery Disease; Hypercholesterolemia; Hyperlipidemia; Atorvastatin; Heart Diseases; Ezetimibe; Dyslipidemias; Intravascular Ultrasound
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Ezetimibe
• Other Study ID Numbers: UMIN000002959