Effects of Chimeric Natriuretic Peptide Versus Placebo in Stable Heart Failure and Moderate Renal Dysfunction
Primary Purpose
Heart Failure, Renal Insufficiency
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
CD-NP
5% Dextrose in Water
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring CD NP, dual receptor, NPR A, NPR B, Adult, aged over 45
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
5% Dextrose in Water
CD-NP
Arm Description
Infusion of D5W
CD-NP as a four hour infusion at 10 ng/kg/min IV
Outcomes
Primary Outcome Measures
Change in renal parameters
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
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
Hemodynamic parameters
• Mean arterial pressure, heart rate
Change in value = [(Value during C2 + Value during C3)/2 ] - Value during C1
Secondary Outcome Measures
Full Information
NCT ID
NCT01407900
First Posted
July 27, 2011
Last Updated
June 16, 2014
Sponsor
John A. Schirger
Collaborators
National Institutes of Health (NIH)
1. Study Identification
Unique Protocol Identification Number
NCT01407900
Brief Title
Effects of Chimeric Natriuretic Peptide Versus Placebo in Stable Heart Failure and Moderate Renal Dysfunction
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 Type
Interventional
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Withdrawn
Why Stopped
New technique for administration of drug, this is the old technique of administration.
Study Start Date
January 2014 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
February 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
John A. Schirger
Collaborators
National Institutes of Health (NIH)
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Renal Insufficiency
Keywords
CD NP, dual receptor, NPR A, NPR B, Adult, aged over 45
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
5% Dextrose in Water
Arm Type
Placebo Comparator
Arm Description
Infusion of D5W
Arm Title
CD-NP
Arm Type
Active Comparator
Arm Description
CD-NP as a four hour infusion at 10 ng/kg/min IV
Intervention Type
Drug
Intervention Name(s)
CD-NP
Other Intervention Name(s)
Chimeric natriuretic peptide
Intervention Description
CD-NP as a four hour infusion at 10 ng/kg/min IV
Intervention Type
Drug
Intervention Name(s)
5% Dextrose in Water
Other Intervention Name(s)
D5W
Intervention Description
four hour infusion IV
Primary Outcome Measure Information:
Title
Change in renal parameters
Description
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
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
Title
Change in hormonal parameters
Description
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
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
Title
Change in hemodynamic parameters
Description
Hemodynamic parameters
• Mean arterial pressure, heart rate
Change in value = [(Value during C2 + Value during C3)/2 ] - Value during C1
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Schirger, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Effects of Chimeric Natriuretic Peptide Versus Placebo in Stable Heart Failure and Moderate Renal Dysfunction
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