CD-NP in Subjects With Stable Chronic Heart Failure

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
John A. Schirger, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00620308
First received: February 10, 2008
Last updated: September 7, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Stable Chronic Heart Failure
Drug: CD-NP
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]

Enrollment: 19
Study Start Date: June 2008
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Placebo Comparator: Placebo Drug: Placebo
Dextrose 5% in water (the vehicle)

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

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00620308

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Director: John C. Burnett, Jr., MD Mayo Foundation
  More Information

Additional Information:
No publications provided

Responsible Party: John A. Schirger, John Schirger ,MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00620308     History of Changes
Other Study ID Numbers: 07-005523
Study First Received: February 10, 2008
Last Updated: September 7, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 15, 2014