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

June 16, 2014 updated by: John A. Schirger

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

45 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: 5% Dextrose in Water
Infusion of D5W
Drug: 5% Dextrose in Water
four hour infusion IV
Other Names:
  • 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 Names:
  • Chimeric natriuretic peptide

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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
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
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
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
John A. Schirger

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institutes of Health (NIH)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: John Schirger, MD, Mayo Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 27, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 1, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 2, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 17, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 16, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 09-008619

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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