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| ID | Type | Description | Link |
|---|---|---|---|
| R01HL036634 | U.S. NIH Grant/Contract | View source | |
| R01HL084155 | U.S. NIH Grant/Contract | View source | |
| P01HL076611 | U.S. NIH Grant/Contract | View source | |
| UL1RR024150 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| American Heart Association | OTHER |
| Scios, Inc. | INDUSTRY |
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| National Center for Research Resources (NCRR) |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| B-type Natriuretic Peptide (BNP) | Active Comparator | BNP (nesiritide) administered subcutaneously twice daily for 8 weeks at 10 mcg/kg. |
|
| Placebo | Placebo Comparator | Placebo self-administered subcutaneously twice daily for 8 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| B-type Natriuretic Peptide (BNP) | Drug | BNP hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Change in Left Ventricular (LV) Mass Index at 8 Weeks | Baseline and 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Change in Plasma Renin Activity at 8 Weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Horng H. Chen, M.D. | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23122795 | Derived | 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. |
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Participants were recruited from May 2003 to May 2008 at the Mayo Clinic in Rochester, Minnesota.
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| ID | Title | Description |
|---|---|---|
| FG000 | B-type Natriuretic Peptide (BNP) | BNP (nesiritide) hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg. |
| FG001 | Placebo | Placebo self-administered subcutaneously twice daily for 8 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | B-type Natriuretic Peptide (BNP) | BNP (nesiritide) hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg. |
| BG001 | Placebo | Placebo self-administered subcutaneously twice daily for 8 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Per protocol population | Posted | Mean | Standard Deviation | ml/m^2 | Baseline and 8 weeks |
|
Adverse events were collected over the 8 week study period
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BPN Group | BNP (nesiritide) administered subcutaneously twice daily for 8 weeks at 10 mcg/kg. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hypotension | Cardiac disorders | Systematic Assessment | 3 subjects in the BNP group developed hypotension (defined by systolic BP <85 mmHg)or had symptoms of light-headedness or visual disturbances during the baseline visit in the Clinical Research Unit. All recovered w/ adjusted position & fluids. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lightheadedness | Cardiac disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Horng H. Chen | Mayo Clinic | 507-778-2354 | chen.horng@mayo.edu |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D009202 | Cardiomyopathies |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D020097 | Natriuretic Peptide, Brain |
| ID | Term |
|---|---|
| D045265 | Natriuretic Peptides |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
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| NIH |
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| Placebo | Other | Placebo self-administered subcutaneously twice daily for 8 weeks. |
|
Plasma renin is synthesized within circulation or at tissue sites, causing vasoconstriction or vasodilation. |
| Baseline and 8 weeks |
| 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 |
| Change in Heart Rate at 8 Weeks | Heart rate was measured when MRI was performed | Baseline and 8 weeks |
| Change in Blood Pressure at 8 Weeks | Blood pressure was measured during the MRI | Baseline and 8 weeks |
| 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 |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Blood pressure | Systolic blood pressure (SBP) the top number and diastolic blood pressure (DBP)the bottom number in a blood pressure reading, are measured in millimeters of mercury (mmHg) on a scale. | Mean | Standard Deviation | mmHg |
|
| New York Heart Association (NYHA) CHF Classification | NYHA classifications of various stages of Congestive Heart Failure (CHF) help determine the severity. Class I-No symptoms at any level of exertion & no limitation in ordinary physical activity. Class II-Mild symptoms and slight limitation during regular activity. Comfortable at rest. Class III-Noticeable limitation due to symptoms, even during minimal activity; Comfortable only at rest. Class IV-Severe limitations. Symptoms even while at rest. Note: The sum of categorized subjects will not equal the total number of participants enrolled in each arm, because only Class II & III were reported. | Number | participants |
|
| Left Ventricle Ejection Fraction (Echo) | 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 echocardiography. A normal LVEF ranges from 55-70%. A LVEF of 65, for example, means that 65% of the total amount of blood in the left ventricle is pumped out with each heartbeat. | Mean | Standard Deviation | Percentage |
|
| Heart Rate | Heart rate (HR) is a measure of how many times the heart beats per minute. | Mean | Standard Deviation | beats per minute |
|
| Plasma BNP | B-type natriuretic peptide (BNP) is a cardiac hormone that affects cardiovascular function. | Median | Inter-Quartile Range | picograms/milliliter |
|
| Glomerular Filtration Rate | Glomerular Filtration Rate (GFR) is a measure of the flow rate or speed the kidney filters fluid, measured in milliliters per minute per 1.73 m^2 of body-surface area. A lower GFR means the kidney is not filtering normally. An estimated GFR of less than 60 ml/min/1.73 m^2 of body-surface area is considered to be impaired kidney function. | Mean | Standard Deviation | ml/min/1.73 m^2 |
|
| History or concomitant medical conditions | Because participants may have none, one, or more than one medical history or concomitant medical condition, the sum of the history categories will not be the same as the overall number of participants in a given arm of the study. | Number | participants |
|
| Concomitant Medication(s) | The sum of subjects taking a given class of medication will not equal the overall number of participants per arm, because all subjects would possibly not be taking all medication classes. | Number | participants |
|
|
|
|
| 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] | Per protocol population | Posted | Mean | Standard Deviation | E/e' | Baseline and 8 weeks |
|
|
|
|
| Secondary | Change in Plasma Renin Activity at 8 Weeks | Plasma renin is synthesized within circulation or at tissue sites, causing vasoconstriction or vasodilation. | Per protocol population | Posted | Mean | Standard Deviation | nanograms per milliliter per hour | Baseline and 8 weeks |
|
|
|
| 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. | Per protocol population | Posted | Mean | Standard Deviation | ml/min/1.73 m^2 of body-surface area | Baseline and 8 weeks |
|
|
|
|
| Primary | Change in Left Ventricular (LV) Mass Index at 8 Weeks | Per protocol population | Posted | Mean | Standard Deviation | mg/m^2 | Baseline and 8 weeks |
|
|
|
|
| Secondary | Change in Heart Rate at 8 Weeks | Heart rate was measured when MRI was performed | Per protocol population | Posted | Mean | Standard Deviation | beats per minute | Baseline and 8 weeks |
|
|
|
| Secondary | Change in Blood Pressure at 8 Weeks | Blood pressure was measured during the MRI | Per protocol population | Posted | Mean | Standard Deviation | mmHg | Baseline and 8 weeks |
|
|
|
| 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). | Per protocol population | Posted | Mean | Standard Deviation | percentage | Baseline and 8 weeks |
|
|
|
| 3 |
| 24 |
| 20 |
| 24 |
| EG001 | Placebo | Placebo self-administered subcutaneously twice daily for 8 weeks | 1 | 21 | 17 | 21 |
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| lightheadedness | Cardiac disorders | Systematic Assessment |
|
| visual disturbances | Eye disorders | Systematic Assessment |
|
| worsening heart failure symptoms | Cardiac disorders | Systematic Assessment |
|
| Shortness of Breath and Fatigue | Cardiac disorders | Systematic Assessment |
|
| Injection site sting/itchy | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Flu-like symptoms | General disorders | Systematic Assessment |
|
| Flushing | Blood and lymphatic system disorders | Systematic Assessment |
|
| Loose stools | Gastrointestinal disorders | Systematic Assessment |
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| Atrial Fibrillation | Cardiac disorders | Systematic Assessment |
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| Hyperkalemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Edema | Blood and lymphatic system disorders | Systematic Assessment |
|
| GI bleed prior to study drug administration | Gastrointestinal disorders | Systematic Assessment |
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| Increased voiding | Renal and urinary disorders | Systematic Assessment |
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| Choledocholithiasis | Hepatobiliary disorders | Systematic Assessment | Gall stone in bile duct was accompanied by fever and elevated liver function test result. |
|
| Head congestion and productive cough | Infections and infestations | Systematic Assessment |
|
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| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |