UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000003307
Receipt number R000003994
Scientific Title Probucol Trial for Secondary Prevention of Atherosclerotic Events in Patients with Prior Coronary Heart Disease, PROSPECTIVE
Date of disclosure of the study information 2010/03/09
Last modified on 2020/05/26 11:00:28

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Basic information

Public title

Probucol Trial for Secondary Prevention of Atherosclerotic Events in Patients with Prior Coronary Heart Disease, PROSPECTIVE

Acronym

Probucol Trial for Secondary Prevention of Atherosclerotic Events (PROSPECTIVE)

Scientific Title

Probucol Trial for Secondary Prevention of Atherosclerotic Events in Patients with Prior Coronary Heart Disease, PROSPECTIVE

Scientific Title:Acronym

Probucol Trial for Secondary Prevention of Atherosclerotic Events (PROSPECTIVE)

Region

Japan Asia(except Japan)


Condition

Condition

Dyslipidemia with high LDL cholesterol (LDL-C) levels, Coronary artery disease

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

NO


Objectives

Narrative objectives1

To evaluate the additional effect of probucol with other lipid-lowering drugs for the prevention of cerebrovascular and cardiovascular events in patients with prior coronary events and high LDL cholesterol level

Basic objectives2

Safety,Efficacy

Basic objectives -Others


Trial characteristics_1

Confirmatory

Trial characteristics_2

Explanatory

Developmental phase

Phase III


Assessment

Primary outcomes

Cerebrovascular or cardiovascular events and the duration from the enrollment.
Following diseases were recognized;
1) death due to cardiovascular diseases including sudden death
2) nonfatal myocardial infarction
3) nonfatal cerebral stroke (excluding transient ischemic attack, TIA)
4) hospitalization for unstable angina
5) hospitalization for heart failure
6) coronary revascularization (percutaneous coronary interventions, PCI or coronary artery bypass graft, CABG)

Key secondary outcomes

1) All deaths
2) All cardiovascular and cerebrovascular diseases
3) Event free survival time
4) Levels of the mean intima media thickness(IMT) of carotid arteries and their changes
5) Levels of max IMT in common or internal carotid arteries and their changes
6) Severe adverse events and their frequency


Base

Study type

Interventional


Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

YES

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration


Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Continuing the former lipid lowering therapy

Interventions/Control_2

Adding probucol with the former lipid lowering therapy

Interventions/Control_3


Interventions/Control_4


Interventions/Control_5


Interventions/Control_6


Interventions/Control_7


Interventions/Control_8


Interventions/Control_9


Interventions/Control_10



Eligibility

Age-lower limit

20 years-old <=

Age-upper limit


Not applicable

Gender

Male and Female

Key inclusion criteria

1) Patients who have been diagnosed as dyslipidemia with high LDL-C level
2) Patients who are taking lipid lowering drugs
3) Patients whose LDL-C level was from 100 to 200 mg/dl by the blood test within 8 weeks before the informed consents (LDL-C should be calculated by the Friedewald formula: LDL-C= TC-HDL-C-TG/5)
4) Patients who have a history of following coronary heart diseases;
myocardial infarction or angina pectoris, and whose onset of the disease was more than 3 months before
CABG which was performed more than 3 months before
PCI which was undergone more than nine months before or no restenosis which was diagnosed by the follow-up coronary angiography, 6-9 months after PCI
5) Patients who are suffering from mild to moderate heart failure. (NYHA classification I or II)
6) Patients who are over 20 years old at the time of informed consent
7) Patients whose hepatic and renal functions are normal, AST<100 IU/L, ALT<100 IU/L, serum creatinine<1.5 IU/L, data from the blood test within 4 weeks before the time of informed consents
8) Patients who have given written informed consent for participating in this study

Key exclusion criteria

1) Patients who have taken probucol within 6 months before the time of informed consents
2) Patients who are currently taking cyclosporin
3) Patients who have a past history of hypersensitivity reactions to probucol
4) Patients who have already been diagnosed as familial hypercholesterolemia based on NICE Clinical Guideline 71 (Atherosclerosis 2003;168:1-14)
5) Patients whose TG level was over 400 mg/dl within 8 weeks before the time of informed consents
6) Patients whose HbA1c level was over 8 % by the latest blood test
7) Patients who have electrocardiographically been confirmed to have frequent multifocal ventricular arrhythmia
8) Patients who have been confirmed to have atrial fibrillation (Af) including paroxysmal Af
9) Patients whose QTc interval in resting electrocardiogram was >450 msec in males or >470 msec in females, respectively
10) Patients who have congestive heart failure or unstable angina
11) Patients who have been participating in other clinical trials
12) Patients who are pregnant, lactating or have the possibility of pregnancy or the wish of pregnancy within this study period
13) Patients whom were considered inappropriate by the doctors for participation in the current study

Target sample size

860


Research contact person

Name of lead principal investigator

1st name Shizuya
Middle name
Last name Yamashita

Organization

Osaka University Hospital

Division name

Department of Cardiovascular Medicine

Zip code

565-0871

Address

Yamadaoka 2-15, Suita, Osaka, Japan

TEL

06-6879-3633

Email

shizu@cardiology.med.osaka-u.ac.jp


Public contact

Name of contact person

1st name Daisaku
Middle name
Last name Masuda

Organization

Osaka University Graduate School of Medicine

Division name

Department of Cardiovascular Medicine

Zip code

565-0871

Address

Yamadaoka 2-2, Suita, Osaka, Japan

TEL

06-6879-3633

Homepage URL

http://www.ibri-kobe.org/

Email

masuda@cardiology.med.osaka-u.ac.jp


Sponsor or person

Institute

Osaka University Graduate School of Medicine

Institute

Department

Personal name



Funding Source

Organization

Foundation for Biomedical Research and Innovation

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Japan


Other related organizations

Co-sponsor


Name of secondary funder(s)



IRB Contact (For public release)

Organization

Osaka University Hospitaal

Address

2-2 Yamaadaoka Suita Osaka

Tel

06-6879-5111

Email

rinri@hp-crc.osaka-u.ac.jp


Secondary IDs

Secondary IDs

NO

Study ID_1


Org. issuing International ID_1


Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions

大阪大学医学部附属病院(大阪府)、京都大学医学部附属病院(京都府)、千葉大学医学部付属病院(千葉県)、順天堂大学医学部附属順天堂医院(東京都)、東邦大学医療センター大橋病院(千葉県)、東邦大学医療センター佐倉病院(千葉県)、国立循環器病センター(大阪府)、中国労災病院(広島県)、山口大学医学部附属病院(山口県)、桜橋渡辺病院(大阪府)、医療法人社団 湖東記念病院(滋賀県)、大阪赤十字病院(大阪府)、りんくう総合医療センター市立泉佐野病院(大阪府)、社会福祉法人恩賜財団済生会支部大阪府済生会千里病院(大阪府)、独立行政法人国立病院機構 京都医療センター(京都府)、健保連大阪中央病院(大阪府)、医療法人 川崎病院(兵庫県)、済生会習志野病院(千葉県)、近畿大学医学部附属病院(大阪府)、
大阪警察病院(大阪府)、国保松戸市立病院(千葉県)、日本大学医学部附属病院(東京都)、神戸大学医学部附属病院(兵庫県)、神戸市立医療センター中央市民病院(兵庫県)、独立行政法人 労働者健康福祉機構 関西労災病院(兵庫県)、大津赤十字病院(滋賀県)、兵庫医科大学附属病院(兵庫県)
その他、順次追加の予定である


Other administrative information

Date of disclosure of the study information

2010 Year 03 Month 09 Day


Related information

URL releasing protocol

http://www.ibri-kobe.org/

Publication of results

Unpublished


Result

URL related to results and publications

https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_55327/_article

Number of participants that the trial has enrolled

876

Results

Patients were randomly assigned to two treatment groups and followed up for more than 3 years. The primary end point was a composite of cerebrovascular and cardiovascular events, its incidence of the primary end point showed a trend to be lower in the probucol group compared with that in the control group despite reduced HDL-C without serious adverse events.

Results date posted

2020 Year 05 Month 26 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results

2020 Year 04 Month 24 Day

Baseline Characteristics

PROSPECTIVE is a multicenter, randomized, prospective study that recruited 876 Japanese patients with CHD and dyslipidemia with an low-density lipoprotein (LDL)-cholesterol (HDL-C) level of > 140 mg/dL without medication or those treated with lipid-lowering drugs.

Participant flow

Lipid-lowering agents were administered during the study period in the control group (n=438), and probucol 500 mg/day was added to lipid-lowering therapy in the probucol group (n=438). Patients were randomly assigned to two treatment groups by adjusting the LDL-C level and presence of diabetes and hypertension and followed up for more than 3 years.

Adverse events

There was no significant difference in the frequencies of SAEs between the two groups.

Outcome measures

The primary end point was a composite of cerebrovascular and cardiovascular events (cardiovascular disease death including sudden death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, hospitalization for heart failure, or coronary revascularization). The secondary end point was carotid intima-media thickness in a subset of patients. The incidence of the primary end point showed a trend to be lower in the probucol group compared with that in the control group despite reduced HDL-C without serious adverse events. Anti-atherogenic effects of probucol may be attributed to its potent antioxidative function and enhancement of reverse cholesterol transport. Since there was no statistical significance between the probucol and control groups despite a marked reduction of HDL-C, further studies on the clinical outcomes of probucol on top of conventional therapy may be necessary in the future

Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2009 Year 09 Month 30 Day

Date of IRB

2009 Year 11 Month 06 Day

Anticipated trial start date

2010 Year 03 Month 01 Day

Last follow-up date

2016 Year 02 Month 28 Day

Date of closure to data entry

2016 Year 02 Month 28 Day

Date trial data considered complete

2018 Year 03 Month 28 Day

Date analysis concluded

2018 Year 12 Month 31 Day


Other

Other related information



Management information

Registered date

2010 Year 03 Month 09 Day

Last modified on

2020 Year 05 Month 26 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000003994


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name