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

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ClinicalTrials.gov Identifier: NCT01407900
Recruitment Status : Withdrawn (New technique for administration of drug, this is the old technique of administration.)
First Posted : August 2, 2011
Last Update Posted : June 17, 2014
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
John A. Schirger, Mayo Clinic

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Heart Failure Renal Insufficiency Drug: CD-NP Drug: 5% Dextrose in Water Phase 1

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2014
Actual Primary Completion Date : February 2014
Actual Study Completion Date : February 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure
U.S. FDA Resources

Arm Intervention/treatment
Placebo Comparator: 5% Dextrose in Water
Infusion of D5W
Drug: 5% Dextrose in Water
four hour infusion IV
Other Name: D5W
Active Comparator: CD-NP
CD-NP as a four hour infusion at 10 ng/kg/min IV
Drug: CD-NP
CD-NP as a four hour infusion at 10 ng/kg/min IV
Other Name: Chimeric natriuretic peptide



Primary Outcome Measures :
  1. 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 ]

    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


  2. 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 ]

    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


  3. 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 ]

    Hemodynamic parameters

    • Mean arterial pressure, heart rate

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




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Ages Eligible for Study:   45 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01407900


Sponsors and Collaborators
John A. Schirger
National Institutes of Health (NIH)
Investigators
Principal Investigator: John Schirger, MD Mayo Clinic

Responsible Party: John A. Schirger, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01407900     History of Changes
Other Study ID Numbers: 09-008619
First Posted: August 2, 2011    Key Record Dates
Last Update Posted: June 17, 2014
Last Verified: June 2014

Keywords provided by John A. Schirger, Mayo Clinic:
CD NP
dual receptor
NPR A
NPR B
Adult, aged over 45

Additional relevant MeSH terms:
Heart Failure
Renal Insufficiency
Heart Diseases
Cardiovascular Diseases
Kidney Diseases
Urologic Diseases