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This study has been withdrawn prior to enrollment.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:
Collaborator:
Information provided by (Responsible Party):
John A. Schirger, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01407900
First received: July 27, 2011
Last updated: June 16, 2014
Last verified: June 2014
  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
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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 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 ] [ 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



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

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Both
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
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: NCT01407900

Sponsors and Collaborators
John A. Schirger
Investigators
Principal Investigator: John Schirger, MD Mayo Clinic
  More Information

No publications provided

Responsible Party: John A. Schirger, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01407900     History of Changes
Other Study ID Numbers: 09-008619
Study First Received: July 27, 2011
Last Updated: June 16, 2014
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on October 23, 2014