Clinical trial NCT01407900: Effects of Chimeric Natriuretic Peptide Versus Placebo in Stable Heart Failure and Moderate Renal Dysfunction
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Heart Failure
Renal Insufficiency
Keywords: CD NP
dual receptor
NPR A
NPR B
Adult, aged over 45
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2011-08-02
Enrollment: 0
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* BMI \>38

Primary outcomes:
measure: Change in renal parameters
timeFrame: 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
measure: Change in hormonal parameters
timeFrame: 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
measure: Change in hemodynamic parameters
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Mayo Clinic
name: John Schirger, MD
role: PRINCIPAL_INVESTIGATOR
References: