A Human Physiologic Study to Evaluate the Renal and Neurohumoral Effects of Dual NPR-A and NPR-B Activation With a Novel Chimeric Natriuretic Peptide (CD-NP)in Subjects With Stable Chronic Heart Failure and Moderate Renal Dysfunction
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 主要终点
- Change in hemodynamic parameters
研究概览
简要总结
The overall aim is to conduct a human physiologic study to assess the renal and neurohumoral effects of CD-NP vs placebo in older subjects with stable chronic systolic heart failure and moderate renal dysfunction.
详细描述
The investigators will evaluate the renal and neurohumoral effects of dual receptor (NPR-A and NPR-B) activation with CD-NP. This is a clinically relevant patient population who is at increased risk of developing diuretic resistance during the treatment of HF exacerbations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and non-pregnant female with stable chronic HF of primary cardiac etiology, resting left ventricular ejection fraction (LVEF) ≤ 40 % documented within the last 2 years.
- •Moderate renal dysfunction with creatinine clearance of 30-60 ml.min-1.1.73m-2, as calculated by Cockcroft-Gault formula24 and adjusted for body surface area within the past year or at screening, or requirement for dialysis.
- •Be willing to provide informed consent.
排除标准
- •Known allergy or other adverse reactions to exogenous natriuretic peptides (CD-NP or its components, nesiritide, other natriuretic peptides, or related compounds).
- •Women who are pregnant, or breast-feeding, on hormonal contraceptives or hormone replacement therapy. (Women should be in the post-menopausal state, defined as the absence of menses for ≥ 1 year and serum follicle-stimulating hormone ≥ 20 IU/L; or should be previously sterilized defined as bilateral tubal occlusion for ≥ 6 months, bilateral oophorectomy, or complete hysterectomy)
- •Having received nesiritide for within 7 days prior to prior to entry into the study.
- •Having received any investigational drug or device within 30 days prior to entry into the study.
- •Clinically unstable patients (e.g. systolic blood pressure < 90 mmHg, ongoing requirement for vasopressors or mechanical circulatory support, or mechanical ventilation).
- •Recent hospitalization for decompensated HF or recent defibrillation for cardiac resuscitation within 30 days prior to randomization.
- •Prior organ transplantation, being on a waiting list for organ transplantation, or ongoing requirement for long-term vasoactive support.
- •Prior requirement for dialysis or ultrafiltration
- •Active urinary tract infection
- •Patients with guarded prognosis who are unlikely to derive meaningful benefit from CD-NP.
- •Use of sulfonamides, non-steroidal anti-inflammatory drugs, probenecid, or other drugs that are known to alter renal function within one week of the first dose of CD-NP or placebo.
- •Presence of cardiac lesions or comorbidities that may contraindicate the use of natriuretic peptides, such as clinically significant cardiac valvular stenosis, hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or uncorrected congenital heart disease that contraindicates the use of vasodilators.
- •History of blood pressure > 190/115 mmHg or unexplained syncope within the past 3 months.
- •Symptomatic carotid artery disease, known critical carotid stenosis, or stroke within the past 3 months
- •Clinically significant renal artery stenosis
- •Baseline hemoglobin < 10.0 g/dl.
- •Serum sodium < 130 mEq/L, potassium < 3.6 mEq/L, or magnesium < 1.7 mEq/L.
- •Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at least 5 times the upper limit of normal or bilirubin at least 3 times the upper limit of normal
- •History of alcohol abuse within the past 6 months.
- •Consumption of a phosphodiesterase-5 inhibitor (sildenafil, vardenafil, or tadalafil) within 72 hours of receiving CD-NP or placebo.
- •Inability to communicate effectively with study personnel.
研究组 & 干预措施
5% Dextrose in Water
Infusion of D5W
干预措施: 5% Dextrose in Water (Drug)
CD-NP
CD-NP as a four hour infusion at 10 ng/kg/min IV
干预措施: CD-NP (Drug)
结局指标
主要结局
Change in hemodynamic parameters
时间窗: 1-hour period before drug or placebo infusion (baseline) and average of two 2-hour periods of drug or placebo infusion collected in a 5-hour period on the study day
Hemodynamic parameters • Mean arterial pressure, heart rate Change in value = \[(Value during C2 + Value during C3)/2 \] - Value during C1
Change in renal parameters
时间窗: 1-hour period before drug or placebo infusion (baseline) and average of two 2-hour periods of drug or placebo infusion collected in a 5-hour period on the study day
Renal parameters * Glomerular filtration rate, tubular function * Renal plasma flow * Urine output * Urinary sodium and potassium excretion * Urinary NGAL for early, acute alterations in renal function Change in value = \[(Value during C2 + Value during C3)/2 \] - Value during C1
Change in hormonal parameters
时间窗: 1-hour period before drug or placebo infusion (baseline) and average of two 2-hour periods of drug or placebo infusion collected in a 5-hour period on the study day
Hormonal parameters * Plasma cyclic GMP, ANP, BNP, NT-proBNP, CNP, renin, angiotensin II, aldosterone, and norepinephrine * Urinary cyclic GMP, ANP, BNP, CNP * Plasma and urinary CD-NP Change in value = \[(Value during C2 + Value during C3)/2 \] - Value during C1
次要结局
未报告次要终点
研究者
John A. Schirger
MD
Mayo Clinic