UMIN-CTR Clinical Trial

Public title

Justification for Atherosclerosis Regression Treatment
[JART Extension Study]

Acronym

JART
[JART Extension Study]

Scientific Title

Justification for Atherosclerosis Regression Treatment
[JART Extension Study]

Scientific Title:Acronym

JART
[JART Extension Study]

Region

Japan

Condition

Hypercholesterolemia

Classification by specialty

Cardiology

Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To evaluate the effect of intensive Rosuvastatin therapy for lipids on regression of carotid artery intima-media thickness (IMT) compared to conventional Pravastatin therapy for patients with hypercholesterolemia .
Furthermore, to investigate long-term safety and efficacy in the intensive therapy group.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Not applicable

Primary outcomes

% change from baseline in mean-IMT at the end of 24 months.

Key secondary outcomes

1) Time to % change in mean-IMT.
2) Time to % change in max-IMT of the distal wall of the common carotid artery (IMT-Cmax-distal wall).
3) Time to % change in IMT-Cmax of common carotid artery, IMT-Bmax of carotid sinus, and IMT-Imax of internal carotid artery.
4) Percentage of cases in which mean-IMT decreased at the end of 12 months and 24 months.
5) Time to % change in LDL-C / HDL-C ratio.
6) Percentage of cases in which LDL-C / HDL-C ratio <= 1.5 at the end of 12 months and 24 months.
7) Percentage of cases in which LDL-C / HDL-C ratio <= 2.0 at the end of 12 months and 24 months.
8) Correlation between LDL-C / HDL-C ratio and max-IMT.
9) Correlation between LDL-C / HDL-C ratio and mean-IMT.
10) Time to % change of serum lipids (LDL-C, HDL-C, and TG), HbA1c, systolic blood pressure, and diastolic blood pressure.
11) JASGL2007 achievement ratio according to the management target level of LDL-C .
12) Cumulative incidence and content of cardiovascular and cerebral vascular events.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Active

Stratification

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

5 mg Rosuvastatin will be orally administered once daily for two years.
Target LDL-C levels are 80 mg/dL for primary prevention, and 70 mg/dL for secondary prevention. If these levels are not achieved, doses are gradually increased (e.g. Rosuvastatin (10 mg/day), Rosuvastatin (10 mg/day) + another hypolipidemic drug).

Interventions/Control_2

10 mg Pravastatin will be orally administered once daily for two years. Target LDL-C levels are in compliance with JASGL2007. If these levels are not achieved, doses are gradually increased (e.g. Pravastatin (20 mg/day), Pravastatin (20 mg/day) + another hypolipidemic drug).

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

(1) Hypercholesterolemia (LDL-C >= 140 mg/dL)
(2) Patients with a max-IMT level of 1.1 mm or greater
(3) Hospital stay or hospital visit: no object.
(4) Patients who are able to submit written consent agreement by themselves.

Key exclusion criteria

(1) Patients that require lipid-lowering therapy other than the study drug or specified lipid-lowering drugs (anion-exchange resin, inhibitor of probucol, and ethyl icosapentate (EPA))
(2) Patients who have taken statins within one month before the start of the clinical trial.
(3) Patients suspected of having serious carotid artery stenosis (greater than 80%) or having serious calcification.
(4) Patients with familial hypercholesterolemia or secondary hypercholesterolemia.
(5) Patients with fasting serum TG >= 400 mg/dL.
(6) Patients with a history of sensitivity to statins.
(7) Patients with uncontrolled hypertension.
(8) Patients with Type I diabetes or uncontrolled Type II diabetes.
(9) Patients who have experienced myocardial infarction or a cerebral stroke within 3 months or Patients with serious heart failure (NYHA class III to IV).
(10) Patients with active hepatic disease.
(11) Patients with renal disorder (Cr >= 2.0 mg/dL or Ccr < 30 mL/min/1.73m2).
(12) Patients with CK > 500 IU/L.
(13) Patients currently being treated with cyclosporine.
(14) Patients that are pregnant or potentially pregnant, patients breast-feeding, or patients aiming to become pregnant during the clinical trial.
(15) Patients with or suspected of having a malignant tumor, or patients with a history of malignant tumor except for the patients in whom recurrences have not been confirmed by routine observation after treatment.
(16) Patients with hypothyroidism, hereditary muscular diseases (muscular dystrophy, etc.) or familial history of these diseases. Patients with history of drug-related muscular disorder.
(17) Patients with drug abuse or alcoholic.
(18) Patients who are ineligible in the opinion of the investigator.

Target sample size

400

Name of lead principal investigator

1st name
Middle name
Last name	Ryuji Nohara

Organization

Hirakata Kohsai Hospital

Division name

President, Heart Center

Zip code

Address

1-2-1 Fujisakahigashimachi, Hirakata, Osaka, Japan

TEL

072-858-8233

Email

r-nohara@kkr-hirakoh.jp

Name of contact person

1st name
Middle name
Last name	Toshifumi Kakutani

Organization

JART Study Support Center

Division name

Mebix Inc.

Zip code

Address

Akasaka Intercity, 1-11-44, Akasaka Minato-ku, Tokyo, 107-0052, Japan

TEL

03-6229-8936

Homepage URL

Email

j-art@mebix.co.jp

Institute

Japan Atherosclerosis Regressive Treatment Study Group

Institute

Department

Personal name

Organization

Japan Heart Foundation

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2011

Year

06

Month

14

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

Number of participants that the trial has enrolled

Results

Nohara R et al. : Circ J. 2012;76(1): 221-229

Nohara R et al. : Circ J 2013; 77(6): 1526 -1533

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2008

Year

04

Month

03

Day

Date of IRB

Anticipated trial start date

2008

Year

06

Month

01

Day

Last follow-up date

2011

Year

12

Month

01

Day

Date of closure to data entry

2012

Year

01

Month

31

Day

Date trial data considered complete

2012

Year

02

Month

07

Day

Date analysis concluded

2012

Year

02

Month

21

Day

Other related information

Registered date

2011

Year

06

Month

14

Day

Last modified on

2013

Year

08

Month

30

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006788