UMIN-CTR Clinical Trial

Public title

Ezetimibe lipid loWering Trial On PreventIon of Atherosclerosis in 75 or older

Acronym

EWTOPIA75

Scientific Title

Ezetimibe lipid loWering Trial On PreventIon of Atherosclerosis in 75 or older

Scientific Title:Acronym

EWTOPIA75

Region

Japan

Condition

Hyper-LDL-cholesterolemia

Classification by specialty

Medicine in general	Hepato-biliary-pancreatic medicine	Cardiology
Endocrinology and Metabolism	Hematology and clinical oncology	Nephrology
Neurology	Geriatrics

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To investigate the preventive effects of a cholesterol absorption inhibitor, ezetimibe on cardiovascular events in old patients

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

Composite cardiovascular events
(1)Cardiac sudden death
(2)Fatal myocardial infarction
(3)Non-fatal myocardial infarction
(4)PCI or CABG
(5)Fatal stroke
(6)Non-fatal stroke

Key secondary outcomes

(1)
Composite coronary events (cardiac sudden death, fatal myocardial infarction or non-fatal myocardial infarction)
Cardiac sudden death
Fatal or non-fatal myocardial infarction
PCI or CABG
Fatal or non-fatal stroke
Fatal stroke
Non-fatal stroke
Fatal or non-fatal cerebral infarction
Fatal cerebral infarction
Non-fatal cerebral infarction
TIA
Fatal or non-fatal cerebral hemorrhage
Fatal cerebral hemorrhage
Non-fatal cerebral hemorrhage
CAS or CEA
Revascularization for PAD (EVT or bypass operation)
Aortic dissection
Rupture of aortic aneurysm
Operation for aortic aneurysm
(2)
All-cause death
Cardiovascular death (cardiac sudden death, fatal myocardial infarction or fatal stroke)
Non-cardiovascular death
Death for cancer
(3)
All-cause hospitalization
Hospitalization for cardiovascular causes
Hospitalization for non-cardiovascular causes
(4)
Cancer
Femoral neck fracture
Dementia
MMSE
GDS15
ADL (TMIG Index for Competence)
Admission to nursing homes
(5)
Adverse events
(6)
Cost

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Active

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Behavior,custom

Interventions/Control_1

Ezetimibe and diet

Interventions/Control_2

Diet

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

75

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

(1) High-risk outpatients with hyper-LDL-cholesterolemia (serum LDL-cholesterol levels>140mg/dL) aged 75 years and older (at the time of written informed consent) of the both sexes (LDL-cholesterol levels are calculated with Friedewald Formula).

(2) At least one of the following factors
1. DM
2. Hypertension
3. Low-HDL-cholesterolemia
4. Hypertriglyceridemia
5. Current smoking
6. History of cerebral infarction
7. PAD

Key exclusion criteria

(1) Serum TG level> 400 mg/dL
(2) History of myocardial infarction
(3) History of PCI or CABG
(4) Angina pectoris requiring treatment
(5) Recent history of stroke(within 6 months)
(6) 1. AST>100 IU/L 2. ALT>100 IU/L 3. liver chirosis
(7) Serum creatinine level >3.0 mg/dL
(8) Cancer
(9) Dementia
(10) Familial hyperchoresterolemia
(11) Atrial fibrillation
(12) Allergy to ezetimibe
(13) Patients participating in other clinical trials
(14) Patients inappropriate for the trial judged by investigators

Target sample size

6000

Name of lead principal investigator

1st name	Yasuyoshi
Middle name
Last name	Yasuyoshi Ouchi

Organization

Japanese Geriatric Society
Toranomon Hospital

Division name

-

Zip code

105-8470

Address

2-2-2, toranomon, minatoku, Tokyo

TEL

03-3588-1111

Email

ewtopia@csp.or.jp

Name of contact person

1st name	Yoji
Middle name
Last name	Mitadera

Organization

EWTOPIA75 investigators

Division name

EWTOPIA75 office

Zip code

169-0051

Address

1-1-7, nisiwaseda, sinnjyukuku, Tokyo

TEL

0120-750-741

Homepage URL

http://csp.or.jp/ld/ewtopia/

Email

ewtopia@csp.or.jp

Institute

Japanese Geriatric Society
Public Health Research Foundation

Institute

Department

Personal name

Organization

Public Health Research Foundation

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Public Health Research Foundation

Address

1-1-7,Nishiwaseda,Shinjuku,Tokyo,Japan

Tel

03-5287-5070

Email

rinri@phrf.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

2009

Year

05

Month

21

Day

URL releasing protocol

https://www.phrf.jp/csp/csp-ld/ewtopia/

Publication of results

Published

URL related to results and publications

https://www.ahajournals.org/doi/suppl/10.1161/CIRCULATIONAHA.118.039415

Number of participants that the trial has enrolled

3796

Results

Overall, 3796 patients were enrolled between May 2009 and December 2014, and 1898 each were randomly assigned to ezetimibe versus control. Median follow-up was 4.1 years.
Ezetimibe reduced the incidence of the primary outcome (HR, 0.66; 95% CI, 0.50-0.86; P=0.002).

Results date posted

2023

Year

06

Month

19

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

2019

Year

09

Month

17

Day

Baseline Characteristics

Mean age at baseline was 80.6 years for the 2 trial groups. Female patients, never smoke patients, patients with hypertension, middle-risk (1 or 2 risk factors) patients, as well as statin and calcium antagonist users were predominant.

Participant flow

Overall, 3796 patients were enrolled between May 2009 and December 2014, and 1898 each were randomly assigned to ezetimibe versus control. Median follow-up was 4.1 years.

Adverse events

Ezetimibe was not associated with all-cause mortality.

Outcome measures

Ezetimibe reduced the incidence of the primary outcome (HR, 0.66; 95% CI, 0.50-0.86; P=0.002). Regarding the secondary outcomes, the incidences of composite cardiac events (HR, 0.60: 95% CI, 0.37-0.98: P=0.039) and coronary revascularization (HR, 0.38: 95% CI, 0.18-0.79: P=0.007) were lower in the ezetimibe group than in the control group; however, there was no difference in the incidence of stroke, allcause mortality, or adverse events between trial groups.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Main results already published

Date of protocol fixation

2009

Year

02

Month

25

Day

Date of IRB

2009

Year

02

Month

25

Day

Anticipated trial start date

2009

Year

05

Month

01

Day

Last follow-up date

2016

Year

03

Month

31

Day

Date of closure to data entry

2017

Year

10

Month

31

Day

Date trial data considered complete

2017

Year

12

Month

31

Day

Date analysis concluded

2018

Year

10

Month

03

Day

Other related information

Registered date

2009

Year

05

Month

21

Day

Last modified on

2023

Year

06

Month

19

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002426