CD-NP in Subjects With Stable Chronic Heart Failure (CD-NP)
Primary Purpose
Stable Chronic Heart Failure
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CD-NP
Placebo
Sponsored by

About this trial
This is an interventional basic science trial for Stable Chronic Heart Failure
Eligibility Criteria
Inclusion Criteria:
- Male and non-pregnant female subjects, aged 21 or above, with stable chronic HF of primary cardiac etiology, resting left ventricular ejection fraction (LVEF) ≤ 40 % documented within the last 2 years, and New York Heart Association functional class I - III symptoms
- 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.
- 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 longterm vasoactive support.
- 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 5 half-lives prior to 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
- Creatinine clearance (CrCl) < 50 ml.min-1.1.73m-2, as calculated by Cockcroft-Gault formula and adjusted for body surface area within the past year or at screening, or requirement for dialysis.
- 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
Sites / Locations
- Mayo Clinic
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
CD-NP low-dose study drug
CD-NP high-dose study drug
Placebo
Arm Description
Outcomes
Primary Outcome Measures
To assess renal, neurohumoral and non-invasive hemodynamic physiologic parameters
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00620308
Brief Title
CD-NP in Subjects With Stable Chronic Heart Failure
Acronym
CD-NP
Official Title
A Human Physiologic Study to Evaluate the Renal and Neurohumoral Effects of a Novel Chimeric Natriuretic Peptide, CD-NP, in Subjects With Stable Chronic Heart Failure
Study Type
Interventional
2. Study Status
Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
June 2008 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
February 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This human physiologic study will evaluate the effects of a new drug called CD-NP in individuals with stable chronic heart failure, with a focus on evaluating responses of the kidneys and the hormonal system.
Detailed Description
CD-NP is a novel chimeric natriuretic peptide which was created by combining the 22 amino acids of human C-type natriuretic peptide (CNP) and the 15-amino-acid C-terminus of Dendroaspis natriuretic peptide (DNP). The rationale for selecting CNP, a natriuretic peptide of endothelial cell origin, is that it exhibits predominantly venodilating effects, which may minimize systemic hypotension. Moreover, its anti-proliferative action is also a highly desirable property for novel cardiovascular drugs. However, a limitation of CNP is that it does not exert significant renal actions, whereas, DNP is potently natriuretic and diuretic. Thus, CD-NP was synthesized with the goal of combining the above complementary profiles of CNP and DNP into a single chimeric peptide.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stable Chronic Heart Failure
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CD-NP low-dose study drug
Arm Type
Experimental
Arm Title
CD-NP high-dose study drug
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
CD-NP
Intervention Description
One of two dosage levels (20 ng/kg/min and another level to be finalized) as a continuous intravenous infusion for four hours
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Dextrose 5% in water (the vehicle)
Primary Outcome Measure Information:
Title
To assess renal, neurohumoral and non-invasive hemodynamic physiologic parameters
Time Frame
Within the first 24 to 36 hours of the study and at follow-up visits (days 9 and 30)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and non-pregnant female subjects, aged 21 or above, with stable chronic HF of primary cardiac etiology, resting left ventricular ejection fraction (LVEF) ≤ 40 % documented within the last 2 years, and New York Heart Association functional class I - III symptoms
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.
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 longterm vasoactive support.
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 5 half-lives prior to 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
Creatinine clearance (CrCl) < 50 ml.min-1.1.73m-2, as calculated by Cockcroft-Gault formula and adjusted for body surface area within the past year or at screening, or requirement for dialysis.
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John C. Burnett, Jr., MD
Organizational Affiliation
Mayo Foundation
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Links:
URL
http://clinicaltrials.mayo.edu
Description
Mayo Clinic Clinical Trials
Learn more about this trial
CD-NP in Subjects With Stable Chronic Heart Failure
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