Clinical trial NCT00620308: CD-NP in Subjects With Stable Chronic Heart Failure
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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Stable Chronic Heart Failure
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2008-02-21
Enrollment: 19
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: To assess renal, neurohumoral and non-invasive hemodynamic physiologic parameters
timeFrame: Within the first 24 to 36 hours of the study and at follow-up visits (days 9 and 30)
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Foundation
name: John C. Burnett, Jr., MD
role: STUDY_DIRECTOR
References: