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

NCT01407900 | Withdrawn Phase 1

• 1 other identifier: 09-008619
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Heart Failure; Renal Insufficiency

Keywords

CD NP; dual receptor; NPR A; NPR B; Adult, aged over 45

Outcome Measures

Primary Outcomes (3)

• 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

  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

• 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

  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

• Change in hemodynamic parameters

  Hemodynamic parameters • Mean arterial pressure, heart rate Change in value = \[(Value during C2 + Value during C3)/2 \] - Value during C1

  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

Study Arms (2)

5% Dextrose in Water

PLACEBO COMPARATOR

Infusion of D5W

Drug: 5% Dextrose in Water

CD-NP

ACTIVE COMPARATOR

CD-NP as a four hour infusion at 10 ng/kg/min IV

Drug: CD-NP

Interventions

CD-NP DRUG

CD-NP as a four hour infusion at 10 ng/kg/min IV

Also known as: Chimeric natriuretic peptide

CD-NP

5% Dextrose in Water DRUG

four hour infusion IV

Also known as: D5W

5% Dextrose in Water

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• John A. Schirger: lead
• National Institutes of Health (NIH): collaborator

MeSH Terms

Conditions

Heart Failure; Renal Insufficiency

Interventions

Glucose; Water

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• John Schirger, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 27, 2011
• First Posted: August 2, 2011
• Study Start: January 1, 2014
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: June 17, 2014

Record last verified: 2014-06