UMIN-CTR Clinical Trial

Public title

Exploration into the lipid management and persistent risk in the patients hospitalized for acute coronary syndrome in Japan

Acronym

Exploration into the lipid management and persistent risk in the patients hospitalized for acute coronary syndrome (EXPLORE-J)

Scientific Title

Exploration into the lipid management and persistent risk in the patients hospitalized for acute coronary syndrome in Japan

Scientific Title:Acronym

Exploration into the lipid management and persistent risk in the patients hospitalized for acute coronary syndrome (EXPLORE-J)

Region

Japan

Condition

Acute Coronary Syndrome (ACS)

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

To assess the current lipid management of patients hospitalized for ACS, and their persistent CV risk despite undergoing current standard therapy

Basic objectives2

Others

Basic objectives -Others

1.To identify the percentage of patients reaching current lipid targets
2.To compare the incidence of MACE between the patients by LDL-C level
3.To determine the prevalence of FH, including both HeFH and HoFH, among patients hospitalized for ACS

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Not applicable

Primary outcomes

The persistent risk will be defined as the incidence of major adverse cardiovascular events (MACE)

Key secondary outcomes

[1] Coronary revascularization based on myocardial ischemia#2
[2] Revascularization excluding the heart
[3] Inpatient treatment due to occurrence or exacerbation of heart failure
[4] Transient ischemic attack (TIA)#3
[5] Acute arterial obstruction
[6] Central retinal artery occlusion
[7] Other adverse events prolonging or requiring hospitalization

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

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)Patients hospitalized for any ACS (Acute ST-segment elevation myocardial infarction: STEMI, Acute non ST-segment elevation myocardial infarction: NSTEMI, Unstable angina :UA)
2)Patients aged equal or over 20 years
3)Written informed consent

Key exclusion criteria

1) ACS accompanied by or precipitated by significant comorbidity.

2) Enrolled other lipid interventional studies

3) Patients with sub-acute stent-thrombosis caused by revascularization procedures.

Target sample size

2000

Name of lead principal investigator

1st name	Masato
Middle name
Last name	Nakamura

Organization

Toho University Ohashi Medical Center

Division name

Cardiovascular Medicine

Zip code

1538515

Address

2-17-6 Ohashi Meguro-ku, Tokyo

TEL

03-3468-1251

Email

explore-j@mebix.co.jp

Name of contact person

1st name	Hiroichi
Middle name
Last name	Yamamoto

Organization

Mebix

Division name

EXPLORE-J office

Zip code

1050001

Address

3-9-21, Toranomon, Minato-ku, Tokyo

TEL

03-4362-4504

Homepage URL

Email

explore-j@mebix.co.jp

Institute

Sanofi K.K.

Institute

Department

Personal name

Organization

Sanofi K.K.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Toho University Ohashi Medical Center IRB

Address

2-17-6 Ohashi Meguro-ku, Tokyo

Tel

03-3468-1251

Email

secretary@oha.toho-u.ac.jp

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

2015

Year

10

Month

02

Day

URL releasing protocol

NA

Publication of results

Published

URL related to results and publications

https://www.jstage.jst.go.jp/article/jat/28/12/28_59543/_article

Number of participants that the trial has enrolled

2016

Results

Two-year incidences of MACE
Overall, MACE occurred in 120 of 1944 patients (6.17%). The most common event was non-fatal ACS requiring hospitalization, which was observed in 80 patients (4.12%).

First MACE by LDL-C subgroup
Two-year incidences of first MACE by LDL-C subgroup were 25 of 254 (9.84%) in the L1 group (LDL-C <70 mg/dL at baseline) and 88 of 1513 (5.82%) in the L2 group (LDL-C >70 mg/dL at baseline).
There was a significant difference between the two groups. (Log-rank test P=0.0040).

Results date posted

2024

Year

10

Month

30

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The mean age was 66.0 years, and 80.3% were male. The mean LDL-C level at first measurement after hospitalization was 121.2 mg/dL. The most common type of ACS was STEMI (61.5%), followed by UAP (22.6%), and NSTEMI (15.9%) .

Participant flow

A total of 2016 patients were enrolled in this study; however, 72 patients were excluded from the analysis population due to failure to obtain informed consent within the time allowance, unapproved informed consent, duplicate entry, no informed consent, erroneous entry and withdrawal due to target case achieved. The analysis population was 1944 patients.

Adverse events

Two-year incidences of MACE
Overall, MACE occurred in 120 of 1944 patients (6.17%). The most common event was non-fatal ACS requiring hospitalization, which was observed in 80 patients (4.12%).

Outcome measures

Primary endpoints
[1] Two-year incidences of MACE
Overall, MACE occurred in 120 of 1944 patients (6.17%). The most common event was non-fatal ACS requiring hospitalization, which was observed in 80 patients (4.12%).

[2] First MACE by LDL-C subgroup
Two-year incidences of first MACE by LDL-C subgroup were 25 of 254 (9.84%) in the L1 group (LDL-C <70 mg/dL at baseline) and 88 of 1513 (5.82%) in the L2 group (LDL-C >70 mg/dL at baseline).
There was a significant difference between the two groups. (Log-rank test P=0.0040).

[3] First MACE by FH/ not-FH subgroup
Two-year incidences of first MACE by subgroup (FH and not-FH) were 1 of 52 (1.92%) in the FH group and 119 of 1892 (6.29%) in the not-FH group.
There was no significant difference between the two groups (p=0.1764).

[4] Factors associated with occurrence of MACE
Analyses in the pre-defined groups A and B were performed to investigate the factors associated with the incidence of MACE. Univariate and multivariate analyses by Cox proportional hazards models were performed.
There were 1752 in the analysis population (event: 113, censoring: 1639).
The factors associated with the incidence of MACE (P<0.05) were age, previous history of CAD, previous history of cerebrovascular accident, medical history of diabetes mellitus (DM), DM in accordance with the guideline, medical history of hypertension, medical history of dialysis, LDL-C <70 vs. >70 mg/dL at baseline, estimated glomerular filtration rate (eGFR) <30 vs. >30 mL/min/1.73m2, and family history of hypercholesterolemia and LDL-C level (reference: first measurement after hospitalization) in univariate analyses.
In multivariate analyses, hazard ratios (HRs) for age >75 (HR 1.814), previous history of CAD (HR 2.234), and eGFR <30 mL/min/1.73m2 (HR 3.143) were significant (P<0.05).
In the patients who underwent FH genetic testing, univariate analyses showed that the factors associated with the incidence of MACE were medical history of dialysis, eGFR <30 vs. >30 mL/min/1.73m2, and PCSK9 (Heterodimer) ng/mL [logarithmic conversion value] .
In multivariate analyses, only the HR for eGFR <30 mL/min/1.73m2 (HR 7.401) was statistically significant (P<0.05).

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2015

Year

01

Month

23

Day

Date of IRB

2015

Year

04

Month

13

Day

Anticipated trial start date

2015

Year

04

Month

21

Day

Last follow-up date

2018

Year

09

Month

20

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Study Design:
Nation-wide, Multi-centre, Prospective Observational study

Patient selection:
Hospitalized, from April 2015 to March 2016, ACS patients in prespecified hospitals

Data collected:
At baseline
-Demography
-Family history
-Physical examination
-Achilles tendon thickness
-Medication and Medical histories
-Diagnosis of FH by physicians
-DNA (for specifically consented patients only)

At baseline and the follow-up timing (Day1, 30, 180, 1yr and 2yr)
-MACE
-Laboratory measurements: LDL-C, HDL-C, Triglycerides, non-HDLC, apoA1, apoB, Lp(a), hs-CRP and PCSK9

Registered date

2015

Year

09

Month

08

Day

Last modified on

2024

Year

10

Month

30

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021916