UMIN-CTR Clinical Trial

Public title

Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) Trial of Cardiovascular Events in High-Risk Hypertensive Patients

Acronym

CASE-J

Scientific Title

Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) Trial of Cardiovascular Events in High-Risk Hypertensive Patients

Scientific Title:Acronym

CASE-J

Region

Japan

Condition

Hypertension

Classification by specialty

Medicine in general

Cardiology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The purpose of this study is to compare an angiotensin II receptor antagonist (candesartan cilexetil– Blopress®) and a calcium channel blocker (amlodipine besilate– Norvasc®/Amlodin®) in terms of the incidence of cardiovascular events among high-risk hypertensive patients.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Phase IV

Primary outcomes

Sudden death: death of endogenous origin within 24 hours after acute onset; Cerebrovascular events: new occurrence or recurrence of a stroke or transient ischemic attack ;
Cardiac events: new occurrence, aggravation, or recurrence of heart failure, angina pectoris, or acute myocardial infarction;
Renal dysfunction: serum creatinine ≥4.0 mg/dl, end stage renal disease, doubling of serum creatinine (however, creatinine ≤2.0 mg/dl is not regarded as an event);
Vascular events: new occurrence or aggravation of dissecting aneurysm of aorta, arteriosclerotic occlusion of peripheral artery

Key secondary outcomes

All deaths
Involution of left ventricular;
hypertrophy (LVMI);
Proportion of the subjects who withdrew from the allocated treatment

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Active

Stratification

YES

Dynamic allocation

NO

Institution consideration

Blocking

YES

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Candesartan cilexetil (Blopress®) administered orally at a dose of 4–8
mg/day. When necessary, the dose was increased up to 12 mg/day. However, in patients with renal impairment, the
drug was started from 2 mg/day and increased up to 8 mg/ day when necessary.
The targets of BP control are as follows,
<60age:SBP<130 DBP<85
60s:SBP<140 DBP<90
70s:SBP<150 DBP<90
80s:SBP<160 DBP<90
Following randomization, patients will be monitored with the appropriate frequency as judged by the collaborating physicians. The dose of the assigned drug can be gradually increased up to the maximum dosage (for candesartan, 12 mg/day) to achieve the therapeutic goals. If not achieved by the maximum dosage of each drug, any antihypertensive drugs other than the angiotensin II receptor antagonist, the calcium channel blocker,
or ACE inhibitors can be added.

Interventions/Control_2

Amlodipine besilate (Norvasc®/
Amlodin®) administered orally at a dose of 2.5–5 mg/day and
increased up to 10 mg/day when necessary.
The targets of BP control are as follows,
<60age:SBP<130 DBP<85
60s:SBP<140 DBP<90
70s:SBP<150 DBP<90
80s:SBP<160 DBP<90
Following randomization, patients will be monitored with the appropriate frequency as judged by the collaborating physicians. The dose of the assigned drug can be gradually increased up to the maximum dosage (for amlodipine, 10 mg/day) to achieve the therapeutic goals. If not achieved by the maximum dosage of each drug, any antihypertensive drugs other than the angiotensin II receptor antagonist, the calcium channel blocker,
or ACE inhibitors can be added.

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

85

years-old

>

Gender

Male and Female

Key inclusion criteria

1.SBP >=140 mmHg in those <70 years old or >=160 mmHg in those >=70 years old or DBP >=90 mmHg in a sitting position on two consecutive measurements at clinic
2.At least one of the following risk factors:
a) SBP >=180 mmHg or DBP >=110 mmHg on two consecutive visits
b) Type 2 diabetes (fasting blood glucose >=126 mg/dl, causal blood glucose >=200 mg/dl, HbA1c >=6.5%, 2h blood glucose on 75gOGTT >=200 mg/dl,or current treatment with hypoglycemic agent)
c) History of cerebral hemorrhage, cerebral infarction, or transient ischemic attack until 6 months prior to the screening
d) Thickness of the posterior wall of left ventricle or thickness of the wall of interventricular septum >=12 mm on echocardiography or Sv1+RV5 >=35 mm on electrocardiography, angina pectoris, and a past history (>=6 months before giving informed consent) of myocardial infarction.
e) Proteinuria >=+1 or renal impairment (serum creatinine >=1.3 mg/dl) within 3 months at the time of giving informed consent.
f) Arteriosclerotic peripheral arterial obstruction (Fontaine class >=2)

Key exclusion criteria

1.SBP ≥200 mmHg or DBP ≥120 mmHg in a sitting position
2.Type I diabetes mellitus
3.History of myocardial infarction or cerebrovascular accidents within 6 months prior to the screening
4.PTCA or CABG done within 6 months of screening or scheduled
5.Current treatment for congestive cardiac failure (NYHA functional class II or severer) or ejection fraction <40%
6.Coronary artery disease requiring beta blocker or calcium channel blocker
7.Atrial fibrillation or atrial flutter
8.Renal dysfunction (serum creatinine ≥3 mg/dl)
9.Hepatic dysfunction (AST and/or ALT ≥100 IU/l)
10.A history of malignant tumor within 5 years of enrollment or suspected
11.Contraindication for candesartan cilexetil or amlodipine besilate
12.Pregnancy, possible pregnancy, or plan to conceive a child within 5 years of enrollment
13.Not suited to the clinical trail as judged by a collaborating physician
14.Inability to give informed consent

Target sample size

4000

Name of lead principal investigator

1st name
Middle name
Last name	Takao Saruta

Organization

Keio University

Division name

School of Medicine

Zip code

Address

Sugimoto Building 2F, 1-12, Shinano-machi, Sinjyuku-ku, Tokyo

TEL

Email

Name of contact person

1st name
Middle name
Last name	Junichi Sakamoto

Organization

Kyoto University

Division name

Epidemiological & Clinical Research Information Management

Zip code

Address

TEL

Homepage URL

Email

sakamoto@pbh.med.kyoto-u.ac.jp

Institute

EBM Collaborating Research Center in Kyoto University

Institute

Department

Personal name

Organization

The Japanese Society of Hypertension

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

YES

Study ID_1

NCT00125463

Org. issuing International ID_1

ClinicalTrials.gov

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2005

Year

10

Month

30

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

Number of participants that the trial has enrolled

Results

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

2001

Year

04

Month

01

Day

Date of IRB

Anticipated trial start date

2001

Year

09

Month

01

Day

Last follow-up date

2005

Year

12

Month

01

Day

Date of closure to data entry

2006

Year

06

Month

01

Day

Date trial data considered complete

2006

Year

08

Month

01

Day

Date analysis concluded

2006

Year

09

Month

01

Day

Other related information

Registered date

2005

Year

10

Month

24

Day

Last modified on

2006

Year

11

Month

01

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000000336