UMIN-CTR Clinical Trial

Public title

Japanese Multicenter Evaluation of LOng- versus short-acting Diuretics In Congestive heart failure

Acronym

J-MELODIC

Scientific Title

Japanese Multicenter Evaluation of LOng- versus short-acting Diuretics In Congestive heart failure

Scientific Title:Acronym

J-MELODIC

Region

Japan

Condition

congestive heart failure

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The mortality and morbidity of heart failure are still high despite emerging evidences that have shown beneficial effects of ACE inhibitor, beta-blocker, ARB, and aldosterone receptor antagonist. Diuretics are the most prescribed in heart failure patients in attenuating symptoms due to fluid retention, and diuretics are recommended as essential medicines in patients with heart failure symptoms and/or fluid retention. However, the effects of a long-term administration of diuretics on morbidity and mortality have not been adequately assessed in the prospective clinical study, and the retrospective analysis did not necessarily indicate the diuretic-induced improvement of mortality. McCurley et al demonstrated the adverse effects of furosemide in a tachycardia-induced heart failure model (J Am Coll Cardiol 2004; 44: 1301-1307). Yoshida et al. demonstrated that the administration of furosemide did not improve mortality rate, while the administration of azosemide, a long-acting loop diuretic, improved mortality rate in a hypertensive heart failure model (Cardiovasc Res 2005; 68: 118-127). If the effects on mortality and/or morbidity of heart failure patients are different among classes of diuretics, we should choose a class to provide better prognosis. Thus, we designed a multicenter prospective study, J-Melodic (Japanese Multicenter Evaluation of LOng- versus short-acting Diuretics In Congestive heart failure) to obtain a clinical evidence about the effects of diuretics in heart failure. The purpose of this study is to compare therapeutic effects of furosemide, a short-acting loop diuretic, and azosemide, a long-acting one, in patients with heart failure, and to test our hypothesis that long-acting diuretics are superior to short-acting types in heart failure.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Explanatory

Developmental phase

Phase IV

Primary outcomes

A composite of cardiovascular death and unplanned admission to hospital for congestive heart failure.

Key secondary outcomes

1. All cause mortality
2. Worsening of the symptoms [that is defined by either a decrease by (a) 1 Mets in the SAS questionnaire score or an increase by (b) I class in the NYHA functional class for at least 3 months as compared with the baseline]
3. An increase in brain natriuretic peptide (BNP) by more than 30% of the value at the randomization in patients with BNP more than or equal to 200 pg/ml at the randomization.
4. Unplanned admission to hospital for congestive heart failure, or a need for modification of the treatment for heart failure (changes in oral medicine for at least one month or addition of intravenous drug(s) for at least 4 hours).

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Active

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

After screening for eligibility and obtaining written informed consent, patients will be randomized to 2 groups in a 1:1 ratio. Patients discontinued taking previous loop diuretic(s) and are directly rolled over to one of the two arms. One arm is azosemide group, and patients will take azosemide 30-60 mg/day without a placebo run-in period. Patients are treated with standard therapy including digitalis, mineralocorticoid receptor blockers, ACE inhibitors, ARB, beta-blockers, and calcium channel blockers. The dose of each diuretic will be appropriately adjusted according to symptoms of each patient, and patients will be maintained for the rest of the study. The planned minimum follow-up period for each patient is 2 years, and SAS evaluation, electrocardiography, chest X-ray and blood sample will be conducted at the study entry and every 12 months after the randomization.

Interventions/Control_2

After screening for eligibility and obtaining written informed consent, patients will be randomized to 2 groups in a 1:1 ratio. Patients discontinued taking previous loop diuretic(s) and are directly rolled over to one of the two arms. One arm is furosemide group, and patients will take furosemide 20-40 mg/day without a placebo run-in period. Patients are treated with standard therapy including digitalis, mineralocorticoid receptor blockers, ACE inhibitors, ARB, beta-blockers, and calcium channel blockers. The dose of each diuretic will be appropriately adjusted according to symptoms of each patient, and patients will be maintained for the rest of the study. The planned minimum follow-up period for each patient is 2 years, and SAS evaluation, electrocardiography, chest X-ray and blood sample will be conducted at the study entry and every 12 months after the randomization.

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. Clinical diagnosis of heart failure based on a slight modification of the Framingham criteria within 6 months before the entry
2. NYHA II or III
3. No change in baseline therapy and symptoms of heart failure within a month
4. Loop diuretic(s) is (are) administered currently
5. Written informed consent was obtained.

Key exclusion criteria

1. Diabetes mellitus that has not been well controlled (fasting blood glucose > 200 mg/dl, HbA1c > 9%)
2. Current symptomatic hypotension
3. Hypertension that has not been controlled to the satisfaction of the investigator
4. Serum creatinine > 2.5 mg/dl
5. Serious liver disease
6. Acute coronary syndrome
7. Any life-threatening acute disease (including patients with implantable cardiac defibrillator)
8. Hemodynamically significant (in the investigators opinion) LV outflow tract obstruction (due to either aortic stenosis or ventricular hypertrophy)
9. Chronic obstructive pulmonary disease or restrictive lung disease
10. Primary pulmonary hypertension or pulmonary hypertension not due to LV dysfunction
11. Acute myocardial infarction or cerebrovascular accident within the last 3 months
12. Percutaneous coronary intervention or open heart surgery within the last 3 months
13. Any change in cardiovascular drug therapy within a month prior to randomization
14. Malignancy
15. Surgery for resecting malignant tumor within 5 years
16. Patients unable to walk without personal aid
17. Serious cerebrovascular disease
18. Patients who require intravenous inotropes
19. Pregnancy
20. Patients who were judged not to be suitable for entry by physicians

Target sample size

300

Name of lead principal investigator

1st name
Middle name
Last name	Tohru Masuyama

Organization

Hyogo College of Medicine

Division name

Cardiovascular Division, Department of Internal Medicine

Zip code

Address

1-1 Mukogawa-cho, Nishinomiya, Hyogo, Japan

TEL

0798-45-6553

Email

Name of contact person

1st name
Middle name
Last name	Takeshi Tsujino

Organization

Hyogo College of Medicine

Division name

Cardiovascular Division, Department of Internal Medicine

Zip code

Address

1-1 Mukogawa-cho, Nishinomiya, Hyogo, Japan

TEL

0798-45-6553

Homepage URL

http://j-melodic.com/

Email

jmelodic@hyo-med.ac.jp

Institute

The J-MELODIC Program Committee

Institute

Department

Personal name

Organization

The ministry of health, labor and welfare, Japan

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

YES

Study ID_1

NCT00355667

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

2006

Year

11

Month

24

Day

URL releasing protocol

http://j-melodic.com/

Publication of results

Unpublished

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

2006

Year

03

Month

17

Day

Date of IRB

Anticipated trial start date

2006

Year

06

Month

01

Day

Last follow-up date

2010

Year

08

Month

01

Day

Date of closure to data entry

2011

Year

01

Month

01

Day

Date trial data considered complete

2011

Year

02

Month

01

Day

Date analysis concluded

Other related information

Registered date

2006

Year

11

Month

23

Day

Last modified on

2011

Year

06

Month

08

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000000637