Cardiac Hormone Replacement With BNP in Heart Failure: A Novel Therapeutic Strategy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Change in Left Ventricular (LV) Volume Index at 8 Weeks
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years
- •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.)
- •New York Heart Association (NYHA) Class I (with previous symptoms of heart failure), Class II and III
- •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.
排除标准
- •Myocardial infarction (MI) within 3 months of screening.
- •Unstable angina within 14 days of screening, or any evidence of myocardial ischemia.
- •Valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis.
- •Sustained ventricular tachycardia (VT) or ventricular fibrillation (V-fib) within 14 days of screening.
- •Second or third degree atrioventricular (AV) block without a permanent cardiac pacemaker.
- •Cerebrovascular accident (CVA) within 3 months of screening, or other evidence of significantly compromised central nervous system (CNS) perfusion.
- •Serum creatinine of >3.0 mg/dL.
- •Serum sodium of <125 milliequivalents per decaLiter (mEq/dL) or > 160 mEq/dL.
- •Serum potassium of < 3.5 mEq/dL or > 5.2 mEq/dL.
- •Serum digoxin level of > 2.0 ng/ml.
- •Systolic pressure of <85 mmHg immediately prior to the first injection of study drug/placebo.
- •LVEF > 35% by within 24 months of screening.
- •Unable to self-administer subcutaneous injection twice a day.
- •Diagnosed with AIDS or known positive HIV titer.
- •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.
- •Received an investigational drug within 1 month prior to dosing.
- •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.
- •In the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any reasons.
- •Patient in atrial fibrillation or who have a pacemaker or implantable cardioverter defibrillator (ICD)
- •Hemoglobin < 10g/dl.
- •Patients with an allergy to iodine.
研究组 & 干预措施
B-type Natriuretic Peptide (BNP)
BNP (nesiritide) administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
干预措施: B-type Natriuretic Peptide (BNP) (Drug)
Placebo
Placebo self-administered subcutaneously twice daily for 8 weeks.
干预措施: Placebo (Other)
结局指标
主要结局
Change in Left Ventricular (LV) Volume Index at 8 Weeks
时间窗: Baseline and 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.
Change in Left Ventricular (LV) Mass Index at 8 Weeks
时间窗: Baseline and 8 weeks
次要结局
- Change in Left Ventricular (LV) Filling Pressure at 8 Weeks(Baseline and 8 weeks)
- Change in Plasma Renin Activity at 8 Weeks(Baseline and 8 weeks)
- Change in Renal Function as Measured by Glomerular Filtration Rate (GFR) at 8 Weeks(Baseline and 8 weeks)
- Change in Heart Rate at 8 Weeks(Baseline and 8 weeks)
- Change in Blood Pressure at 8 Weeks(Baseline and 8 weeks)
- Change in Left Ventricular Ejection Fraction at 8 Weeks(Baseline and 8 weeks)
研究者
Horng Chen
MD, Professor of Medicine
Mayo Clinic