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

Sponsor

Kyoto University (Other)

Overall Status

Completed

CT.gov ID

NCT00242944

Collaborator

Yamaguchi University Hospital (Other), Juntendo University (Other)

307

Enrollment

Locations

Arms

Duration (Months)

102.3

Patients Per Site

3.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Coronary Disease Hypercholesterolemia	Drug: Pitavastatin Drug: Atorvastatin	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

307 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome

Study Start Date :

Nov 1, 2005

Actual Primary Completion Date :

Oct 1, 2007

Actual Study Completion Date :

Mar 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Pitavastatin	Drug: Pitavastatin Pitavastatin 4mg per day
Active Comparator: 2 Atorvastatin	Drug: Atorvastatin Atorvastatin 20mg per day

Arm

Intervention/Treatment

Active Comparator: 1

Pitavastatin

Drug: Pitavastatin

Pitavastatin 4mg per day

Active Comparator: 2

Atorvastatin

Drug: Atorvastatin

Atorvastatin 20mg per day

Outcome Measures

Primary Outcome Measures

plaque volume [one year]

Secondary Outcome Measures

total cholesterol (TC) [one year]
low-density lipoprotein (LDL)-cholesterol (LDL-C) [one year]
high-density lipoprotein (HDL)-cholesterol (HDL-C) [one year]
HDL2-C [one year]
HDL3-C [one year]
remnant like particles-cholesterol (RLP-C) [one year]
small dense LDL-C [one year]
non-HDL-C [one year]
LDL-C/HDL-C [one year]
apolipoprotein AI (apoA-I) [one year]
apoB [one year]
apoE [one year]
apoB/apoA-I [one year]
malondialdehyde-modified LDL (MDA-LDL) [one year]
phospholipids [one year]
lipoprotein(a) [Lp(a)] [one year]
high-sensitivity C-reactive protein (hs-CRP) [one year]
pentraxin 3 [one year]
leukocytes [one year]
coronary plaque area at culprit region [one year]
minimal lumen diameter (MLD) and percent (%) stenosis [one year]
major adverse cardiac events (cardiac death, Q or non-Q myocardial infarction and target vessel revascularization) [one year]
number of deaths from any cause [one year]
frequency of adverse drug reactions [one year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Juntendo University School of Medicine	Bunkyo-ku	Tokyo	Japan	113-8421
2	Yamaguchi University Graduate School of Medicine	Ube	Yamaguchi	Japan	755-8505
3	Kyoto University Graduate School of Medicine	Kyoto		Japan	606-8507

Sponsors and Collaborators

Kyoto University
Yamaguchi University Hospital
Juntendo University

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