Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS)

This study has been completed.
Sponsor:
Collaborators:
Yamaguchi University Hospital
Juntendo University School of Medicine
Information provided by:
Kyoto University
ClinicalTrials.gov Identifier:
NCT00242944
First received: October 20, 2005
Last updated: December 16, 2009
Last verified: June 2008
  Purpose

The purpose of this study is to compare the effects of pitavastatin and atorvastatin on coronary plaque volume in patients with acute coronary syndrome and to clarify the relationship between coronary plaque volume, serum lipids, and inflammation markers in order to determine the significance of intensive lipid lowering therapy in patients with acute coronary syndrome in Japan.


Condition Intervention Phase
Coronary Disease
Hypercholesterolemia
Drug: Pitavastatin
Drug: Atorvastatin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome

Resource links provided by NLM:


Further study details as provided by Kyoto University:

Primary Outcome Measures:
  • plaque volume [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • total cholesterol (TC) [ Time Frame: one year ] [ Designated as safety issue: No ]
  • low-density lipoprotein (LDL)-cholesterol (LDL-C) [ Time Frame: one year ] [ Designated as safety issue: No ]
  • high-density lipoprotein (HDL)-cholesterol (HDL-C) [ Time Frame: one year ] [ Designated as safety issue: No ]
  • HDL2-C [ Time Frame: one year ] [ Designated as safety issue: No ]
  • HDL3-C [ Time Frame: one year ] [ Designated as safety issue: No ]
  • remnant like particles-cholesterol (RLP-C) [ Time Frame: one year ] [ Designated as safety issue: No ]
  • small dense LDL-C [ Time Frame: one year ] [ Designated as safety issue: No ]
  • non-HDL-C [ Time Frame: one year ] [ Designated as safety issue: No ]
  • LDL-C/HDL-C [ Time Frame: one year ] [ Designated as safety issue: No ]
  • apolipoprotein AI (apoA-I) [ Time Frame: one year ] [ Designated as safety issue: No ]
  • apoB [ Time Frame: one year ] [ Designated as safety issue: No ]
  • apoE [ Time Frame: one year ] [ Designated as safety issue: No ]
  • apoB/apoA-I [ Time Frame: one year ] [ Designated as safety issue: No ]
  • malondialdehyde-modified LDL (MDA-LDL) [ Time Frame: one year ] [ Designated as safety issue: No ]
  • phospholipids [ Time Frame: one year ] [ Designated as safety issue: No ]
  • lipoprotein(a) [Lp(a)] [ Time Frame: one year ] [ Designated as safety issue: No ]
  • high-sensitivity C-reactive protein (hs-CRP) [ Time Frame: one year ] [ Designated as safety issue: No ]
  • pentraxin 3 [ Time Frame: one year ] [ Designated as safety issue: No ]
  • leukocytes [ Time Frame: one year ] [ Designated as safety issue: No ]
  • coronary plaque area at culprit region [ Time Frame: one year ] [ Designated as safety issue: No ]
  • minimal lumen diameter (MLD) and percent (%) stenosis [ Time Frame: one year ] [ Designated as safety issue: No ]
  • major adverse cardiac events (cardiac death, Q or non-Q myocardial infarction and target vessel revascularization) [ Time Frame: one year ] [ Designated as safety issue: No ]
  • number of deaths from any cause [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • frequency of adverse drug reactions [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Enrollment: 307
Study Start Date: November 2005
Study Completion Date: March 2008
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Pitavastatin
Drug: Pitavastatin
Pitavastatin 4mg per day
Active Comparator: 2
Atorvastatin
Drug: Atorvastatin
Atorvastatin 20mg per day

Detailed Description:

Previous mega trials have demonstrated that lipid lowering therapy with HMG-CoA reductase inhibitors (statins) reduces the incidence of major cardiovascular events by one-third, thus, the benefit of lipid lowering therapy has been substantiated. Such a benefit is significant especially for patients with coronary heart disease (CHD). The third report of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP-III) has suggested the advantage of more intensive lipid lowering therapy with a goal of reducing LDL-C below 70 mg/dL for such patients categorized as very high risk. In Japan, Japan Atherosclerosis Society (JAS) Guidelines for Diagnosis and Treatment of Atherosclerotic Cardiovascular Diseases 2002 have recommended that an LDL-C goal for patients with coronary heart disease should be below 100 mg/dL. However, there is no satisfactory evidence yet for the need to lower LDL-C level less than the goal prescribed in Japan.

Recently, research on diagnosis of coronary plaque has shown significant advances. The REVERSAL study in patients with a history of CHD, by diagnosis with intravascular ultrasound, suggested that intensive lipid lowering therapy with atorvastatin (80 mg/day) was associated with no growth of plaque (-0.4% compared to baseline), versus therapy with pravastatin (40 mg/day) which showed a slight increase (2.7%) in plaque volume over 18 months. In Japan, the ESTABLISH study, a single center study, indicated that early intensive lipid lowering therapy with atorvastatin (20 mg/day) could induce a significant reduction in plaque volume in patients with acute coronary syndrome. However, this benefit has not been verified in multicenter trials in Japan. Further, no comparative investigation into the effect of various concomitant drugs on coronary plaque has been done.

Pitavastatin is a chemically synthesized statin in Japan which has been marketed since late 2003. Pitavastatin has an LDL-C lowering effect as strong as atorvastatin and also has a superior HDL-C elevating effect; meanwhile, the effect of pitavastatin on coronary plaque has not been reported.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with written consent by their own volition after being provided sufficient explanation for their participation in this clinical trial
  • Patients 20 years or older at the time of their consent
  • Patients with hypercholesterolemia as defined by any of the following criteria:

    • TC >= 220 mg/dL;
    • LDL-C >= 140 mg/dL;
    • Cholesterol-lowering treatment is necessary in accordance with the investigator's judgement when LDL-C >= 100 mg/dL or TC >= 180 mg/dL.
  • Patients who have been diagnosed with acute coronary syndrome
  • Patients with successful percutaneous coronary intervention (PCI) by intravascular ultrasound (IVUS) guidance
  • Patients having coronary plaques (>= 500 µm in thickness or 20% or more in % plaque) at >= 5 mm from the previously treated area in the same branch of coronary artery

Exclusion Criteria:

  • Patients with bypass graft or in-stent restenosis at the site of PCI
  • Patients who had received PCI on the lesion in the past where the evaluation of coronary plaque volume is planned
  • Patients who had plaques in a non-culprit site and might receive PCI during the treatment period
  • Patients receiving lipid-lowering drugs (statins, fibrates, probucol, nicotinic acid or cholesterol absorption inhibitors)
  • Patients with familial hypercholesterolemia
  • Patients with cardiogenic shock
  • Patients receiving cyclosporine
  • Patients with any allergy to pitavastatin or atorvastatin
  • Patients with hepatobiliary disorders
  • Pregnant women, women suspected of being pregnant, or lactating women
  • Patients with renal disorders or undergoing dialysis
  • Patients who are ineligible in the opinion of the investigator
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00242944

Locations
Japan
Juntendo University School of Medicine
Bunkyo-ku, Tokyo, Japan, 113-8421
Yamaguchi University Graduate School of Medicine
Ube, Yamaguchi, Japan, 755-8505
Kyoto University Graduate School of Medicine
Kyoto, Japan, 606-8507
Sponsors and Collaborators
Kyoto University
Yamaguchi University Hospital
Juntendo University School of Medicine
Investigators
Study Chair: Masunori Matsuzaki, MD, PhD Professor of Medicine, Department of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine
Principal Investigator: Hiroyuki Daida, MD Professor of Medicine, Department of Cardiovascular Medicine, Juntendo University School of Medicine
Principal Investigator: Takeshi Kimura, MD Associate Professor of Medicine, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
  More Information

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

Responsible Party: Masunori Matsuzaki, Yamaguchi University Graduate School of Medicine
ClinicalTrials.gov Identifier: NCT00242944     History of Changes
Other Study ID Numbers: H17-49
Study First Received: October 20, 2005
Last Updated: December 16, 2009
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Kyoto University:
Acute coronary syndrome
Hypercholesterolemia
Primary coronary intervention
Hydroxymethylglutaryl-CoA reductase inhibitors
coronary plaque
Angioplasty, Transluminal, Percutaneous Coronary
Ultrasonography, Interventional

Additional relevant MeSH terms:
Coronary Disease
Coronary Artery Disease
Hypercholesterolemia
Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms
Atorvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pitavastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 21, 2014