Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease (REAL-CAD)

• ClinicalTrials.gov Identifier: NCT01042730
• Recruitment Status: Completed
• First Posted: January 6, 2010
• Last Update Posted: May 17, 2021
• Sponsor: Juntendo University
• Collaborators: Tokyo University; Yamaguchi University Hospital; Tohoku University; Kyoto University; Kumamoto University
• Information provided by (Responsible Party): Juntendo University

Study Description

Brief Summary:

The purpose of this study is to evaluate the prevention of cardiovascular disease by moderate cholesterol lowering therapy, pitavastatin 1mg/day or aggressive cholesterol lowering therapy, pitavastatin 4mg/day in patients with stable coronary artery disease.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease	Drug: Pitavastatin 1 mg daily or 4 mg daily	Not Applicable

Detailed Description:

It was already demonstrated by previous clinical trials that statins lower the incidence of death and cardiovascular events in patients with coronary artery disease. However, whether aggressive cholesterol lowering therapy, using high dosage of statins, is more effective than moderate cholesterol lowering therapy for the prevention of cardiovascular events in patients with coronary artery disease has not been studied in Japan.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13054 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease (REAL-CAD)
• Actual Study Start Date: February 2010
• Actual Primary Completion Date: June 2016
• Actual Study Completion Date: November 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Pitavastatin 1 mg daily	Drug: Pitavastatin 1 mg daily or 4 mg daily; Patients who met all inclusion criteria and did not meet exclusion criteria (1) are entered in run-in period, loading pitavastatin 1 mg/day for more than 1 month when informed consent was given. (Primary registration) After 1 month, patients who did not meet exclusion criteria(2) are randomized to take pitavastatin 1 mg/day or 4 mg/day.; Other Name: LIVALO Tablet
Active Comparator: Pitavastatin 4 mg daily	Drug: Pitavastatin 1 mg daily or 4 mg daily; Patients who met all inclusion criteria and did not meet exclusion criteria (1) are entered in run-in period, loading pitavastatin 1 mg/day for more than 1 month when informed consent was given. (Primary registration) After 1 month, patients who did not meet exclusion criteria(2) are randomized to take pitavastatin 1 mg/day or 4 mg/day.; Other Name: LIVALO Tablet

Outcome Measures

Primary Outcome Measures :

1. Occurrence of one of following events(Cardiovascular death, Non-fatal Myocardial Infarction (MI), Non-fatal Cerebral Infarction (CI), Unstable angina requiring urgent hospitalization) [ Time Frame: 3-6 years ]

Secondary Outcome Measures :

1. Composite cardiovascular events [ Time Frame: 3-6 years ]
2. Composite coronary heart disease events [ Time Frame: 3-6 years ]
3. Composite cerebrovascular events [ Time Frame: 3-6 years ]
4. Death events [ Time Frame: 3-6 years ]
5. Heart disease events [ Time Frame: 3-6 years ]
6. Cerebrovascular events [ Time Frame: 3-6 years ]
7. The other events [ Time Frame: 3-6 years ]

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 79 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients who met following all criteria are entered in run-in period, loading pitavastatin 1 mg/day for more than 1 month when informed consent was given. (Primary registration)

• Coronary artery disease patients meeting one of the following events

  • History of Acute Coronary Syndrome (AMI or Unstable angina)
  • History of revascularization (PCI or CABG)
  • Diagnosis of ischemic heart disease and coronary artery stenosis as having 75% or higher stenosis according to the AHA classification

• Hypercholesterolemia patients meeting one of following criteria

  • LDL-C is 140 mg/dL or over
  • LDL-C is 100 mg/dL or over and requiring cholesterol lowering drugs judged by attending physicians
  • Patents receiving cholesterol lowering drugs
• Age (≧20 <80 year-old)
• Patients given written informed consent.

Exclusion Criteria:

Exclusion Criteria(Pre-Run-in period)

• Patients planning revascularization
• Malignant tumor in active phase

• Patients who meet contraindication of LIVALO tablet below

  • Patients who have hypersensitivity to LIVALO tablet
  • Patients who have severe liver dysfunction or biliary atresia
  • Patients who are being treated with cyclosporine
  • Pregnant women, women suspected of being pregnant, or lactating women
• Patients who have heart failure NYHA III or greater
• Patients undergoing dialysis
• Patients with familial hypercholesterolemia
• Patients registered in the other clinical trials
• Patients taking prohibited drugs
• Patients who are ineligible in the opinion of the investigator

Exclusion Criteria(Post-Run-in period)

• LDL-C is 120mg/dL or over after Run-in period
• Patients with occurrence of acute coronary syndrome (AMI or Unstable angina) within 3 months
• Patients who have been undergone PCI or CABG within 3 months
• Compliance is less than 50% in Run-in period
• Patients who met primary endpoint in Run-in period.
• Patients who met adverse events in Run-in period and judged as ineligible in the opinion of the investigator
• Patients who are ineligible in the opinion of the investigator

Contacts and Locations

Locations

Japan

Kyoto University Hospital

Kyoto, Japan, 606-8507

Juntendo University School of Medicine

Tokyo, Japan

Sponsors and Collaborators

Juntendo University

Tokyo University

Yamaguchi University Hospital

Tohoku University

Kyoto University

Kumamoto University

Investigators

• Principal Investigator: Ryozo Nagai, MD, PhD; Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine
• Principal Investigator: Masunori Matsuzaki, MD, PhD; Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Taguchi I, Iimuro S, Iwata H, Takashima H, Abe M, Amiya E, Ogawa T, Ozaki Y, Sakuma I, Nakagawa Y, Hibi K, Hiro T, Fukumoto Y, Hokimoto S, Miyauchi K, Yamazaki T, Ito H, Otsuji Y, Kimura K, Takahashi J, Hirayama A, Yokoi H, Kitagawa K, Urabe T, Okada Y, Terayama Y, Toyoda K, Nagao T, Matsumoto M, Ohashi Y, Kaneko T, Fujita R, Ohtsu H, Ogawa H, Daida H, Shimokawa H, Saito Y, Kimura T, Inoue T, Matsuzaki M, Nagai R. High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial. Circulation. 2018 May 8;137(19):1997-2009. doi: 10.1161/CIRCULATIONAHA.117.032615. Erratum in: Circulation. 2019 Apr 2;139(14):e836.

• Responsible Party: Juntendo University
• ClinicalTrials.gov Identifier: NCT01042730
• Other Study ID Numbers: CSP-LD-09
• First Posted: January 6, 2010
• Last Update Posted: May 17, 2021
• Last Verified: May 2021

Keywords provided by Juntendo University:

Pitavastatin; Coronary Artery Disease; Cardiovascular Disease

Additional relevant MeSH terms:

Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pitavastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Lipid Regulating Agents