CD-NP in Subjects With Stable Chronic Heart Failure (CD-NP)

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

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.

Study Overview

• Status: Completed
• Conditions: Stable Chronic Heart Failure
• Intervention / Treatment: Drug: CD-NP; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. Be willing to provide informed consent.

Exclusion Criteria:

1. Known allergy or other adverse reactions to exogenous natriuretic peptides (CD-NP or its components, nesiritide, other natriuretic peptides, or related compounds).
2. Women who are pregnant, or breast-feeding.
3. Having received nesiritide for within 7 days prior to prior to entry into the study.
4. Having received any investigational drug or device within 30 days prior to entry into the study.
5. Clinically unstable patients (e.g. systolic blood pressure < 90 mmHg, ongoing requirement for vasopressors or mechanical circulatory support, or mechanical ventilation).
6. Recent hospitalization for decompensated HF or recent defibrillation for cardiac resuscitation within 30 days prior to randomization.
7. Prior organ transplantation, being on a waiting list for organ transplantation, or ongoing requirement for longterm vasoactive support.
8. Patients with guarded prognosis who are unlikely to derive meaningful benefit from CD-NP.
9. 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.
10. 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.
11. History of blood pressure > 190/115 mmHg or unexplained syncope within the past 3 months.
12. Symptomatic carotid artery disease, known critical carotid stenosis, or stroke within the past 3 months
13. Clinically significant renal artery stenosis
14. Baseline hemoglobin < 10.0 g/dL.
15. Serum sodium < 130 mEq/L, potassium < 3.6 mEq/L, or magnesium < 1.7 mEq/L.
16. 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
17. 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.
18. History of alcohol abuse within the past 6 months.
19. Consumption of a phosphodiesterase-5 inhibitor (sildenafil, vardenafil, or tadalafil) within 72 hours of receiving CD-NP or placebo.
20. Inability to communicate effectively with study personnel.
21. bmi>38

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Dextrose 5% in water (the vehicle)
Experimental: CD-NP low-dose study drug	Drug: CD-NP; One of two dosage levels (20 ng/kg/min and another level to be finalized) as a continuous intravenous infusion for four hours
Experimental: CD-NP high-dose study drug	Drug: CD-NP; One of two dosage levels (20 ng/kg/min and another level to be finalized) as a continuous intravenous infusion for four hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess renal, neurohumoral and non-invasive hemodynamic physiologic parameters	Within the first 24 to 36 hours of the study and at follow-up visits (days 9 and 30)

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Study Director: John C. Burnett, Jr., MD, Mayo Foundation

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: February 10, 2008
• First Submitted That Met QC Criteria: February 10, 2008
• First Posted (Estimate): February 21, 2008

Study Record Updates

• Last Update Posted (Estimate): September 10, 2012
• Last Update Submitted That Met QC Criteria: September 7, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 07-005523