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

Congestive Heart Failure Clinical Trial

— SubqBNP  

Official title:

Cardiac Hormone Replacement With BNP in Heart Failure: A Novel Therapeutic Strategy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00252187
• Other study ID #: 69-00
• Secondary ID: R01HL036634R01HL
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 10, 2005
• Last updated: December 19, 2012
• Start date: January 2000
• Est. completion date: June 2010

Study information

• Verified date: December 2012
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: June 2010
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy
• Congestive Heart Failure
• Heart Failure

Intervention

Drug:
• B-type Natriuretic Peptide (BNP)
BNP hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.

Other:
• Placebo
Placebo self-administered subcutaneously twice daily for 8 weeks.

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (5)

Lead Sponsor	Collaborator
Horng Chen	American Heart Association, National Center for Research Resources (NCRR), National Heart, Lung, and Blood Institute (NHLBI), Scios, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Left Ventricular (LV) Volume Index at 8 Weeks	LV volume was measured for systolic volume and diastolic volume using a cardiac Magnetic Resonance Imaging (MRI) scan. All cardiac MRI images were reviewed by an independent cardiologist in a blinded fashion.	Baseline and 8 weeks	Yes
Primary	Change in Left Ventricular (LV) Mass Index at 8 Weeks		Baseline and 8 weeks	No
Secondary	Change in Left Ventricular (LV) Filling Pressure at 8 Weeks	Filling pressure determined by ratio of E/e' [Echocardiograph Doppler mitral inflow velocity (E) to mitral annulus tissue Doppler velocity (e') ratio]	Baseline and 8 weeks	No
Secondary	Change in Plasma Renin Activity at 8 Weeks	Plasma renin is synthesized within circulation or at tissue sites, causing vasoconstriction or vasodilation.	Baseline and 8 weeks	No
Secondary	Change in Renal Function as Measured by Glomerular Filtration Rate (GFR) at 8 Weeks	Kidney function was measured by GFR determined by iothalamate clearance. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney measured in milliliters per minute per 1.73 m^2 of body-surface area. A lower GFR means the kidney is not filtering normally.	Baseline and 8 weeks	No
Secondary	Change in Heart Rate at 8 Weeks	Heart rate was measured when MRI was performed	Baseline and 8 weeks	No
Secondary	Change in Blood Pressure at 8 Weeks	Blood pressure was measured during the MRI	Baseline and 8 weeks	No
Secondary	Change in Left Ventricular Ejection Fraction at 8 Weeks	Left Ventricle Ejection Fraction (LVEF)is a clinical parameter used by cardiologists to describe how well the heart is pumping. LVEF is a measure of the amount of blood pumped out of the lower chamber (ventricle) of the heart during a heartbeat, measured by Magnetic Resonance Imaging (MRI).	Baseline and 8 weeks	No

External Links

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