Heart FailurePhase 1NCT01407900
Effects of Chimeric Natriuretic Peptide Versus Placebo in Stable Heart Failure and Moderate Renal Dysfunction
A Phase 1 study testing CD-NP and 5% Dextrose in Water in people with Heart Failure and Renal Insufficiency, run by John A. Schirger.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Heart Failure, Renal Insufficiency
- What is being tested?
- CD-NP and 5% Dextrose in Water
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2014to Feb 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
About this study
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
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.
Read the 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.
- Conditions
- Heart Failure, Renal Insufficiency
- Being tested
- CD-NP, 5% Dextrose in Water
- Keywords
- CD NP, dual receptor, NPR A, NPR B, Adult, aged over 45
- Medical subject headings
- Heart Failure, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD-NPDrug
Also called Chimeric natriuretic peptide
CD-NP as a four hour infusion at 10 ng/kg/min IV
5% Dextrose in WaterDrug
Also called D5W
four hour infusion IV
| Study group | Role | What they receive |
|---|---|---|
| 5% Dextrose in Water | Placebo comparator | Infusion of D5W Receives: Drug: 5% Dextrose in Water |
| CD-NP | Active comparator | CD-NP as a four hour infusion at 10 ng/kg/min IV Receives: Drug: CD-NP |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2011 (estimated)
- Study startJan 2014
- Primary completionFeb 2014
- Study completionFeb 2014
Why it stopped: New technique for administration of drug, this is the old technique of administration.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- John A. Schirger
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor-investigator, John A. Schirger, Mayo Clinic
- Investigators
- John Schirger, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01407900
- Sponsor's protocol ID
- 09-008619
- Status last verified
- Jun 2014
- First submitted
- 27 Jul 2011
- Last updated
- 17 Jun 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01407900
- Acronym / sponsor ID
- 09-008619
- Conditions
- Heart Failure, Renal Insufficiency
- Keywords
- CD NP, dual receptor, NPR A, NPR B, Adult, aged over 45
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: New technique for administration of drug, this is the old technique of administration.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- John A. SchirgerUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Jan 2014
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 2 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 5% Dextrose in Water | Placebo comparator | Drug: 5% Dextrose in WaterInfusion of D5W |
| CD-NP | Active comparator | Drug: CD-NPCD-NP as a four hour infusion at 10 ng/kg/min IV |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (22 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD-NPAlso: Chimeric natriuretic peptideCD-NP as a four hour infusion at 10 ng/kg/min IV | Drug | CD-NP |
| 5% Dextrose in WaterAlso: D5Wfour hour infusion IV | Drug | 5% Dextrose in Water |
Primary outcome
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Schirger, MD principal investigator
Mayo Clinic
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD-NP and 5% Dextrose in Water in people with Heart Failure and Renal Insufficiency, run by John A. Schirger.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2014.