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

This study has been withdrawn prior to enrollment.
(New technique for administration of drug, this is the old technique of administration.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01407900
First Posted: August 2, 2011
Last Update Posted: June 17, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
John A. Schirger, Mayo Clinic
  Purpose
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 Intervention Phase
Heart Failure Renal Insufficiency Drug: CD-NP Drug: 5% Dextrose in Water Phase 1

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by John A. Schirger, Mayo Clinic:

Primary Outcome Measures:
  • 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


  • 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


  • 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



Enrollment: 0
Study Start Date: January 2014
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Information from the National Library of Medicine

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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
  Contacts and Locations
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
  More Information

Responsible Party: John A. Schirger, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01407900     History of Changes
Other Study ID Numbers: 09-008619
First Submitted: July 27, 2011
First Posted: August 2, 2011
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