Cardiac Hormone Replacement With Brain Natriuretic Peptide (BNP) in Heart Failure

NCT ID: NCT00252187

Last Updated: 2012-12-20

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-01-31

Study Completion Date

2010-06-30

Brief Summary

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The purpose of this study is to determine the effects of subcutaneous injection of Human BNP (nesiritide), a hormone produced by the heart, on the pumping ability of the heart, kidney function, and hormonal function in persons with heart failure.

Detailed Description

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The cardiac hormone brain natriuretic peptide (BNP) plays an important role in the pathophysiology of congestive heart failure (CHF). Studies have established that BNP mediates natriuresis, renin and aldosterone (RAAS) inhibition, vasodilation and lusitropism. Acute cardiac hormone replacement with intravenous infusion of BNP has been shown to possess potent vasodilating actions in humans with acute decompensated CHF resulting in improvement of clinical symptoms. Natrecor (nesiritide) a sterile, purified preparation of human BNP is approved by the FDA for intravenous administration in the treatment of patients with acute decompensated congestive heart failure. However, chronic cardiac hormone replacement with BNP as therapeutic strategy in CHF has been limited by the need to administer BNP intravenously. The objective of this study is to define the cardiorenal and humoral actions of short term (eight weeks) chronic cardiac hormone replacement with subcutaneous (SQ) BNP in human NYHA class II-III CHF. Systolic and diastolic function, left ventricular remodeling as assessed by its volume, renal function, neurohumoral profiling and exercise capacity will be assessed prior to and after eight weeks of treatment.

Conditions

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Congestive Heart Failure Cardiomyopathy

Keywords

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Heart failure Natriuretic peptides B-type natriuretic peptide Kidney Nesiritide Natrecor CHF

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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B-type Natriuretic Peptide (BNP)

BNP (nesiritide) administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.

Group Type ACTIVE_COMPARATOR

B-type Natriuretic Peptide (BNP)

Intervention Type DRUG

BNP hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.

Placebo

Placebo self-administered subcutaneously twice daily for 8 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Placebo self-administered subcutaneously twice daily for 8 weeks.

Interventions

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B-type Natriuretic Peptide (BNP)

BNP hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.

Intervention Type DRUG

Placebo

Placebo self-administered subcutaneously twice daily for 8 weeks.

Intervention Type OTHER

Other Intervention Names

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Nesiritide

Eligibility Criteria

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Inclusion Criteria

1. Age \> 18 years
2. Resting left ventricular ejection fraction (LVEF) of 35% or less (determined within 48 months of recruitment by echocardiography, multiple gate acquisition scan (MUGA) or left ventriculogram.)
3. New York Heart Association (NYHA) Class I (with previous symptoms of heart failure), Class II and III
4. Female subjects not menopausal or surgically sterilized will need to have a negative pregnancy test the day before the study day and be on contraception.

Exclusion Criteria

1. Myocardial infarction (MI) within 3 months of screening.
2. Unstable angina within 14 days of screening, or any evidence of myocardial ischemia.
3. Valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis.
4. Sustained ventricular tachycardia (VT) or ventricular fibrillation (V-fib) within 14 days of screening.
5. Second or third degree atrioventricular (AV) block without a permanent cardiac pacemaker.
6. Cerebrovascular accident (CVA) within 3 months of screening, or other evidence of significantly compromised central nervous system (CNS) perfusion.
7. Serum creatinine of \>3.0 mg/dL.
8. Serum sodium of \<125 milliequivalents per decaLiter (mEq/dL) or \> 160 mEq/dL.
9. Serum potassium of \< 3.5 mEq/dL or \> 5.2 mEq/dL.
10. Serum digoxin level of \> 2.0 ng/ml.
11. Systolic pressure of \<85 mmHg immediately prior to the first injection of study drug/placebo.
12. LVEF \> 35% by within 24 months of screening.
13. Unable to self-administer subcutaneous injection twice a day.
14. Diagnosed with AIDS or known positive HIV titer.
15. Other acute or chronic medical conditions or laboratory abnormality, which may increase the risks, associated with study participation or may interfere with interpretation of the data.
16. Received an investigational drug within 1 month prior to dosing.
17. Unable to undergo cardiac magnetic resonance imaging (MRI). Contraindications to MRI include pacemaker or defibrillator, pregnant women, atrial fibrillation or other arrhythmia, cerebral aneurysm clips, or severe claustrophobia.
18. In the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any reasons.
19. Patient in atrial fibrillation or who have a pacemaker or implantable cardioverter defibrillator (ICD)
20. Hemoglobin \< 10g/dl.
21. Patients with an allergy to iodine.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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American Heart Association

OTHER

Sponsor Role collaborator

Scios, Inc.

INDUSTRY

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role collaborator

Horng Chen

OTHER

Sponsor Role lead

Responsible Party

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Horng Chen

MD, Professor of Medicine

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Horng H. Chen, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic

Rochester, Minnesota, United States

Site Status

Countries

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United States

References

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Chen HH, Glockner JF, Schirger JA, Cataliotti A, Redfield MM, Burnett JC Jr. Novel protein therapeutics for systolic heart failure: chronic subcutaneous B-type natriuretic peptide. J Am Coll Cardiol. 2012 Dec 4;60(22):2305-12. doi: 10.1016/j.jacc.2012.07.056. Epub 2012 Nov 1.

Reference Type DERIVED
PMID: 23122795 (View on PubMed)

Other Identifiers

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R01HL036634

Identifier Type: NIH

Identifier Source: secondary_id

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R01HL084155

Identifier Type: NIH

Identifier Source: secondary_id

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P01HL076611

Identifier Type: NIH

Identifier Source: secondary_id

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UL1RR024150

Identifier Type: NIH

Identifier Source: secondary_id

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69-00

Identifier Type: -

Identifier Source: org_study_id