Effects of Chimeric Natriuretic Peptide Versus Placebo in Stable Heart Failure and Moderate Renal Dysfunction

This study is not yet open for participant recruitment.
Verified November 2013 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
John A. Schirger, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01407900
First received: July 27, 2011
Last updated: November 15, 2013
Last verified: November 2013

July 27, 2011
November 15, 2013
January 2014
May 2015   (final data collection date for primary outcome measure)
  • Change in renal parameters [ Time Frame: 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 ] [ Designated as safety issue: No ]

    Renal parameters

    • Glomerular filtration rate, tubular function
    • Renal plasma flow
    • Urine output
    • Urinary sodium and potassium excretion
    • Urinary NGAL for early, acute alterations in renal function

    Change in value = [(Value during C2 + Value during C3)/2 ] - Value during C1

  • Change in hormonal parameters [ Time Frame: 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 ] [ Designated as safety issue: No ]

    Hormonal parameters

    • Plasma cyclic GMP, ANP, BNP, NT-proBNP, CNP, renin, angiotensin II, aldosterone, and norepinephrine
    • Urinary cyclic GMP, ANP, BNP, CNP
    • Plasma and urinary CD-NP

    Change in value = [(Value during C2 + Value during C3)/2 ] - Value during C1

  • Change in hemodynamic parameters [ Time Frame: 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 ] [ Designated as safety issue: No ]

    Hemodynamic parameters

    • Mean arterial pressure, heart rate

    Change in value = [(Value during C2 + Value during C3)/2 ] - Value during C1

Same as current
Complete list of historical versions of study NCT01407900 on ClinicalTrials.gov Archive Site
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Not Provided
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Effects of Chimeric Natriuretic Peptide Versus Placebo in Stable Heart Failure and Moderate Renal Dysfunction
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

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.

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
  • Heart Failure
  • Renal Insufficiency
  • Drug: CD-NP
    CD-NP as a four hour infusion at 10 ng/kg/min IV
    Other Name: Chimeric natriuretic peptide
  • Drug: 5% Dextrose in Water
    four hour infusion IV
    Other Name: D5W
  • Placebo Comparator: 5% Dextrose in Water
    Infusion of D5W
    Intervention: Drug: 5% Dextrose in Water
  • Active Comparator: CD-NP
    CD-NP as a four hour infusion at 10 ng/kg/min IV
    Intervention: Drug: CD-NP
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
28
July 2015
May 2015   (final data collection date for primary outcome measure)

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
Both
45 Years and older
No
Contact: Jacque Wanek, RN 507-266-5640 wanek.jacqueline@mayo.edu
Contact: Sherry Benike, RN 507-266-3629
United States
 
NCT01407900
09-008619
No
John A. Schirger, Mayo Clinic
John A. Schirger
National Institutes of Health (NIH)
Principal Investigator: John Schirger, MD Mayo Clinic
Mayo Clinic
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP