Clinical trial NCT00252187: Cardiac Hormone Replacement With Brain Natriuretic Peptide (BNP) in Heart Failure
Official title: Cardiac Hormone Replacement With BNP in Heart Failure: A Novel Therapeutic Strategy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Congestive Heart Failure
Cardiomyopathy
Keywords: Heart failure
Natriuretic peptides
B-type natriuretic peptide
Kidney
Nesiritide
Natrecor
CHF
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: American Heart Association
name: Scios, Inc.
name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Center for Research Resources (NCRR)
First posted: 2005-11-11
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Left Ventricular (LV) Volume Index at 8 Weeks
timeFrame: Baseline and 8 weeks
measure: Change in Left Ventricular (LV) Mass Index at 8 Weeks
timeFrame: Baseline and 8 weeks
Secondary outcomes:
measure: Change in Left Ventricular (LV) Filling Pressure at 8 Weeks
timeFrame: Baseline and 8 weeks
measure: Change in Plasma Renin Activity at 8 Weeks
timeFrame: Baseline and 8 weeks
measure: Change in Renal Function as Measured by Glomerular Filtration Rate (GFR) at 8 Weeks
timeFrame: Baseline and 8 weeks
measure: Change in Heart Rate at 8 Weeks
timeFrame: Baseline and 8 weeks
measure: Change in Blood Pressure at 8 Weeks
timeFrame: Baseline and 8 weeks
measure: Change in Left Ventricular Ejection Fraction at 8 Weeks
timeFrame: Baseline and 8 weeks
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Horng H. Chen, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.