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

NCT ID: NCT01042730

Last Updated: 2021-05-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 13054 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2017-11-30

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.

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.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Pitavastatin 1 mg daily

Group Type: ACTIVE_COMPARATOR

Pitavastatin 1 mg daily or 4 mg daily

Intervention Type: DRUG

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.

Pitavastatin 4 mg daily

Group Type: ACTIVE_COMPARATOR

Pitavastatin 1 mg daily or 4 mg daily

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

LIVALO Tablet

Eligibility 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

• 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

• 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tokyo University

OTHER

Sponsor Role: collaborator

Yamaguchi University Hospital

OTHER

Sponsor Role: collaborator

Tohoku University

OTHER

Sponsor Role: collaborator

Kyoto University

OTHER

Sponsor Role: collaborator

Kumamoto University

OTHER

Sponsor Role: collaborator

Juntendo University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ryozo Nagai, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine

Masunori Matsuzaki, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine

Locations

Kyoto University Hospital

Kyoto, , Japan

Juntendo University School of Medicine

Tokyo, , Japan

Countries

Japan

References

Yoshiki Y, Ozaki Y, Abe M, Ismail TF, Takahashi H, Akao M, Kawai H, Muramatsu T, Harada M, Ohta M, Hashimoto Y, Shiki Y, Koshikawa M, Miyajima K, Takatsu H, Niwa Y, Kawashima N, Ozaki R, Tsuboi N, Iimuro S, Iwata H, Sakuma I, Nakagawa Y, Hibi K, Hiro T, Fukumoto Y, Hokimoto S, Miyauchi K, Ogawa H, Daida H, Shimokawa H, Izawa H, Kimura T, Nagai R; REAL-CAD investigators. Influence of Worsening Renal Function and Baseline Chronic Kidney Disease on Clinical Outcomes in Patients With Chronic Coronary Syndromes: Insights From the REAL-CAD Study. J Am Heart Assoc. 2025 Jan 21;14(2):e034627. doi: 10.1161/JAHA.124.034627. Epub 2025 Jan 17.

Reference Type: DERIVED

PMID: 39818975 (View on PubMed)

Iwata H, Miyauchi K, Naito R, Iimuro S, Ozaki Y, Sakuma I, Nakagawa Y, Hibi K, Hiro T, Fukumoto Y, Hokimoto S, Saito Y, Ogawa H, Shimokawa H, Daida H, Kimura T, Nagai R. Significance of Persistent Inflammation in Patients With Chronic Coronary Syndrome: Insights From the REAL-CAD Study. JACC Adv. 2024 Jun 5;3(7):100996. doi: 10.1016/j.jacadv.2024.100996. eCollection 2024 Jul.

Reference Type: DERIVED

PMID: 39130048 (View on PubMed)

Sakuma M, Iimuro S, Shinozaki T, Kimura T, Nakagawa Y, Ozaki Y, Iwata H, Miyauchi K, Daida H, Suwa S, Sakuma I, Nishihata Y, Saito Y, Ogawa H, Matsuzaki M, Ohashi Y, Taguchi I, Toyoda S, Inoue T, Nagai R. Optimal target of LDL cholesterol level for statin treatment: challenges to monotonic relationship with cardiovascular events. BMC Med. 2022 Nov 14;20(1):441. doi: 10.1186/s12916-022-02633-5.

Reference Type: DERIVED

PMID: 36372869 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29735587 (View on PubMed)

Other Identifiers

CSP-LD-09

Identifier Type: -

Identifier Source: org_study_id