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

This study has been completed.
Sponsor:
Collaborators:
American Heart Association
Scios, Inc.
Information provided by (Responsible Party):
Horng Chen, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00252187
First received: November 10, 2005
Last updated: December 19, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Congestive Heart Failure
Cardiomyopathy
Drug: B-type Natriuretic Peptide (BNP)
Other: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Cardiac Hormone Replacement With BNP in Heart Failure: A Novel Therapeutic Strategy

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Change in Left Ventricular (LV) Volume Index at 8 Weeks [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Change in Left Ventricular (LV) Mass Index at 8 Weeks [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Left Ventricular (LV) Filling Pressure at 8 Weeks [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
    Filling pressure determined by ratio of E/e' [Echocardiograph Doppler mitral inflow velocity (E) to mitral annulus tissue Doppler velocity (e') ratio]

  • Change in Plasma Renin Activity at 8 Weeks [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
    Plasma renin is synthesized within circulation or at tissue sites, causing vasoconstriction or vasodilation.

  • Change in Renal Function as Measured by Glomerular Filtration Rate (GFR) at 8 Weeks [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Change in Heart Rate at 8 Weeks [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
    Heart rate was measured when MRI was performed

  • Change in Blood Pressure at 8 Weeks [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
    Blood pressure was measured during the MRI

  • Change in Left Ventricular Ejection Fraction at 8 Weeks [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
    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).


Enrollment: 45
Study Start Date: January 2000
Study Completion Date: June 2010
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: B-type Natriuretic Peptide (BNP)
BNP (nesiritide) administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
Drug: B-type Natriuretic Peptide (BNP)
BNP hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
Other Name: Nesiritide
Placebo Comparator: Placebo
Placebo self-administered subcutaneously twice daily for 8 weeks.
Other: Placebo
Placebo self-administered subcutaneously twice daily for 8 weeks.
Other Name: Placebo

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00252187

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Horng Chen
American Heart Association
Scios, Inc.
Investigators
Principal Investigator: Horng H. Chen, M.D. Mayo Clinic
  More Information

Additional Information:
No publications provided by Mayo Clinic

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Horng Chen, MD, Professor of Medicine, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00252187     History of Changes
Other Study ID Numbers: 69-00, R01HL036634, R01HL084155, P01HL076611, UL1RR024150
Study First Received: November 10, 2005
Results First Received: November 20, 2012
Last Updated: December 19, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
Heart failure
Natriuretic peptides
B-type natriuretic peptide
Kidney
Nesiritide
Natrecor
CHF

Additional relevant MeSH terms:
Heart Failure
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases
Hormones
Natriuretic Peptide, Brain
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014