Comparison of Long- and Short-acting Diuretics in Congestive Heart Failure

NCT00355667 | Completed Phase 4 DMC

• 1 other identifier: H18-Junkanki(seishu)-ippan-046
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Congestive Heart Failure

Keywords

diuretics; furosemide; azosemide; congestive heart failure

Outcome Measures

Primary Outcomes (1)

• a composite of cardiovascular death and unplanned admission to hospital for congestive heart failure

  2 years

Secondary Outcomes (4)

• all cause mortality

  2 years

• worsening of the symptoms (that is defined by either a decrease by <1 Mets in the SAS questionnaire score or an increase by >I class in the NYHA functional class for at least 3 months as compared with the baseline)

  2 years

• an increase in brain natriuretic peptide (BNP) by > 30% of the value at the randomization in patients with BNP < 200 pg/ml at the randomization

  2 years

• 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)

  2 years

Study Arms (2)

A

ACTIVE COMPARATOR

Patients with chronic heart failure with NYHA II or III are given furosemide.Patients discontinued taking previous loop diuretic(s) and were directly rolled over to the arm with furosemide 20-40 mg/day, without a placebo run-in period. The dose of each diuretic was appropriately adjusted according to symptoms of each patient, and patients were maintained for the rest of the study. Thereafter, patients were reviewed every 2 to 8 weeks. The planned minimum follow-up period for each patient was 2 years, and electrocardiography, chest X-ray and blood sample were conducted at the study entry and every 12 months after the randomization.

Drug: furosemide

B

ACTIVE COMPARATOR

Patients with chronic heart failure with NYHA II or III are given azosemide.Patients discontinued taking previous loop diuretic(s) and were directly rolled over to the arm with azosemide 30-60 mg/day without a placebo run-in period. The dose of azosemide was appropriately adjusted according to symptoms of each patient, and patients were maintained for the rest of the study. Thereafter, patients were reviewed every 2 to 8 weeks. The planned minimum follow-up period for each patient was 2 years, and electrocardiography, chest X-ray and blood sample were conducted at the study entry and every 12 months after the randomization.

Drug: azosemide

Interventions

furosemide DRUG

Patients with chronic heart failure receive furosemide and other standard treatment/

Also known as: Lasix

A

azosemide DRUG

Patients with chronic heart failure receive azosemide and other standard treatment.

Also known as: Daiart

B

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of heart failure based on a slight modification of the Framingham criteria as previously described within 6 months before the entry
• Current status of heart failure is NYHA II or III.
• Currently, loop diuretic(s) is (are) administered.
• No change in baseline therapy and symptoms of heart failure within a month

You may not qualify if:

• Current symptomatic hypotension
• Hypertension that has not been controlled to the satisfaction of the investigator
• Hemodynamically significant (in the investigators opinion) LV outflow tract obstruction (due to either aortic stenosis or ventricular hypertrophy)
• Acute coronary syndrome
• Primary pulmonary hypertension or pulmonary hypertension not due to LV dysfunction
• Serious cerebrovascular disease
• Acute myocardial infarction within the last 3 months
• Patients who require intravenous inotropes
• Cerebrovascular accident within the last 3 months
• Percutaneous coronary intervention or open heart surgery within the last 3 months
• On the waiting list for percutaneous coronary intervention or open heart surgery
• Serum creatinine \> 2.5 mg/dl
• Serious liver disease
• Any change in cardiovascular drug therapy within a month prior to randomization
• History of chronic obstructive pulmonary disease or restrictive lung disease

Sponsors & Collaborators

• Hyogo Medical University: lead
• Ministry of Health, Labour and Welfare, Japan: collaborator

Study Sites (1)

The Hospital of Hyogo College of Medicine

Nishinomiya, Hyōgo, 663-8501, Japan

Location

Related Publications (3)

• Yoshida J, Yamamoto K, Mano T, Sakata Y, Nishio M, Ohtani T, Hori M, Miwa T, Masuyama T. Different effects of long- and short-acting loop diuretics on survival rate in Dahl high-salt heart failure model rats. Cardiovasc Res. 2005 Oct 1;68(1):118-27. doi: 10.1016/j.cardiores.2005.05.023.

  PMID: 16002057 BACKGROUND

• J-MELODIC Program Committee. Rationale and design of a randomized trial to assess the effects of diuretics in heart failure: Japanese Multicenter Evaluation of Long- vs Short-Acting Diuretics in Congestive Heart Failure (J-MELODIC). Circ J. 2007 Jul;71(7):1137-40. doi: 10.1253/circj.71.1137.

  PMID: 17587724 BACKGROUND

• Masuyama T, Tsujino T, Origasa H, Yamamoto K, Akasaka T, Hirano Y, Ohte N, Daimon T, Nakatani S, Ito H. Superiority of long-acting to short-acting loop diuretics in the treatment of congestive heart failure. Circ J. 2012;76(4):833-42. doi: 10.1253/circj.cj-11-1500.

  PMID: 22451450 RESULT

MeSH Terms

Conditions

Heart Failure

Interventions

Furosemide; azosemide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds

Study Officials

• Tohru Masuyama, MD, PhD

  Cardiovascular Division, Hyogo College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiovascular Division, Department of Internal Medicine

Study Record Dates

• First Submitted: July 21, 2006
• First Posted: July 24, 2006
• Study Start: June 1, 2006
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: August 18, 2016

Record last verified: 2016-08

Locations

JP (1)