Heart FailurePhase 1/2Aim 3 BNP/PDEVNCT00972569
Low Dose Intravenous (IV) Infusion of BNP in the Presence and Absence of Acute Type V Phosphodiesterase (PDE V) in Improving Renal Function in Hospitalized Chronic Heart Failure (CHF) Patients With Renal Dysfunction
A Phase 1/2 study testing BNP and PDE-V and BNP in people with Heart Failure and Renal Dysfunction, run by Mayo Clinic.
Trial summary
The purpose of the study is to determine if low doses of BNP can improve renal function in people with chronic heart failure with renal dysfunction, also to determine whether Sildenafil assists with improvement. This study will enroll only hospitalized patients with heart failure. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Renal Dysfunction
- What is being tested?
- BNP and PDE-V and BNP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- Oct 2009to Dec 2019
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients admitted to St Mary's Hospital, Mayo Clinic Rochester MN with NYHA class III-IV decompensated CHF with renal dysfunction as Calculated creatinine clearance of equal or less than 60 ml/min but greater than 20 ml/min using the Cockcroft-Gault formula.
Who cannot join
- Cause of acute renal dysfunction can be reasonably ascribed to factors other than heart failure or its treatment
- Known intrinsic renal diseases or renal artery stenosis of =>50%
- Patients taking Nitrates within the previous 24 hours
- Patients needing emergency coronary revascularization or those who may have rapidly changing cardiac function (i.e. patients with acute myocardial infarction or shock)
- Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period
- Systolic blood pressure < 90 mmHg or cardiogenic shock.
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- Requirement of pressors for maintenance of blood pressure.
- Intra-aortic blood pump use.
- History of significant uncorrected renal artery stenosis as defined by >50% stenosis.
- Severe aortic or mitral stenosis or significant LV outflow tract obstruction. Hgb < 10 mg/dL
- Pregnant or nursing women.
- Contraindication to nesiritide.
- Inability to have NSAID dose held for up to 30 hours, if being treated with these medications.
- Administration of radiocontrast medium within 7 days of enrollment or anticipated use of such agents during the study
About this study
Official title: Specific Aims 3: Define in Hospitalized Decompensated CHF Patients With Renal Dysfunction, the Renal Actions of Low Dose Intravenous Infusion of BNP in the Presence and Absence of Acute PDE V Inhibition in Improving Renal Function
The purpose of the study is to determine if low doses of BNP can improve renal function in people with chronic heart failure with renal dysfunction, also to determine whether Sildenafil assists with improvement. This study will enroll only hospitalized patients with heart failure.
Read the detailed description
The broad objective of this protocol is to advance our understanding of the pathophysiological mechanisms of human Cardiorenal Syndrome (CRS) with a specific emphasis upon the biological interaction between diuretic therapy, the renin-angiotensin-aldosterone-system (RAAS) and cyclic 3'-5'-guanosine monophosphate (cGMP) pathway.
Chronic heart failure (CHF) as a result of left ventricular systolic dysfunction is a clinical syndrome with high mortality and morbidity. Renal dysfunction is a common and progressive complication of CHF and despite growing recognition of the frequent presentation of combined cardiac and renal dysfunction, or "Cardiorenal Syndrome (CRS)", its underlying pathophysiology is not well understood, with a lack of consensus as to its appropriate management.
The main objective of this study is to extend the findings of the applicant's studies in both human and experimental CHF and determine if low dose intravenous (IV) (0.005/Kg/min) administration of BNP in hospitalized decompensated CHF patients with renal dysfunction would improve the renal function. Furthermore, based on our preliminary data, we also sought to assess if PDE V inhibition potentiated these renal enhancing actions.
Hypothesis: Low dose IV infusion of BNP in hospitalized decompensated CHF patients with CRS will enhance renal and humoral functions as compared to standard therapy, which will be further potentiated by PDEV inhibition as evident by:
Increased sodium excretion, Increased creatinine clearance Decreased plasma creatinine and blood urea nitrogen Suppression of the renin-angiotensin-aldosterone system, Increased renal cGMP generation
- Conditions
- Heart Failure, Renal Dysfunction
- Being tested
- BNP and PDE-V, BNP
- Keywords
- BNP with or without PDE-V in heart failure
- 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.
BNP and PDE-VDrug
Also called nesiritide (Natrecor), Viagra
low dose BNP 0.025 u/kg/min for 3 hours then 0.005ug/kg/min 45 hours PDE-V 12.5 mg 4 time points
BNPDrug
Also called Nesiritide (Natrecor)
low dose BNP at 0.025 u/kg/min if tolerated then at 0.005 ug/kg/min for 45 hours
| Study group | Role | What they receive |
|---|---|---|
| BNP with PDE-V | Active comparator | BNP (Nesiritide) will be infused starting at 0.0025 g/Kg/min IV for 3 hours, if tolerated increased to 0.005 g/kg/min for 45 hours without bolus with PDEV inhibition, they will also receive Sildenafil 12.5 mg at timepoints 0,12, 24 and 36 hours Receives: Drug: BNP and PDE-V |
| BNP (Nesiritide) will be infused at 0.005 u/Kg/min IV for 48 h | Active comparator | BNP (Nesiritide) will be infused at 0.025 ug/Kg/min IV for 3 hours then 0.005ug/kg/min 45 hours without bolus. No PDE-V is given. Receives: Drug: BNP |
| standard care | No intervention | Patients randomized to this group will continue to receive therapy at the discretion of the heart failure specialist who is managing the patient (with the exception of BNP and low dose dopamine). Blood and Urine will be collected after the patient has been randomized for 48 hours |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint for this aim will be a comparison of the 3 groups for the percent change in creatinine clearance, and blood urea nitrogen from baseline to 48 hours.
Measured: each blood and urine collections 4 time points
Secondary outcomes (1)
The secondary endpoints for this aim will be a comparison of the 3 groups for the percent change in plasma, sodium excretion, aldosterone, and renal cGMP generation from baseline line to 48 hours
Measured: each blood and urine collection at 4 time points
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2009 (estimated)
- Study startOct 2009
- Primary completionJun 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Horng Chen, Mayo Clinic
- Investigators
- Dr Horng H Chen, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00972569
- Sponsor's protocol ID
- 09-003303
- Other IDs
- 1R01HL08415501A2
- Acronym
- Aim 3 BNP/PDEV
- Status last verified
- Jan 2020
- First submitted
- 3 Sep 2009
- Last updated
- 18 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Hubers SA, Benike SL, Johnson BK, McKie PM, Scott C, Chen HH. Renal Effects of Combination Phosphodiesterase V Inhibition and Low-Dose B-Type Natriuretic Peptide in Acute Heart Failure: A Randomized Clinical Trial. Circ Heart Fail. 2024 Dec;17(12):e011761. doi: 10.1161/CIRCHEARTFAILURE.124.011761. Epub 2024 Nov 8.
PubMed 39513267
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Specific Aims 3: Define in Hospitalized Decompensated CHF Patients With Renal Dysfunction, the Renal Actions of Low Dose Intravenous Infusion of BNP in the Presence and Absence of Acute PDE V Inhibition in Improving Renal Function
- ClinicalTrials.gov ID
- NCT00972569
- Acronym / sponsor ID
- Aim 3 BNP/PDEV / 09-003303
- Conditions
- Heart Failure, Renal Dysfunction
- Keywords
- BNP with or without PDE-V in heart failure
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Oct 2009 (actual)
- Primary completion
- Jun 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 7 Sep 2009 (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 purpose of the study is to determine if low doses of BNP can improve renal function in people with chronic heart failure with renal dysfunction, also to determine whether Sildenafil assists with improvement. This study will enroll only hospitalized patients with heart failure.
Detailed description
The broad objective of this protocol is to advance our understanding of the pathophysiological mechanisms of human Cardiorenal Syndrome (CRS) with a specific emphasis upon the biological interaction between diuretic therapy, the renin-angiotensin-aldosterone-system (RAAS) and cyclic 3'-5'-guanosine monophosphate (cGMP) pathway.
Chronic heart failure (CHF) as a result of left ventricular systolic dysfunction is a clinical syndrome with high mortality and morbidity. Renal dysfunction is a common and progressive complication of CHF and despite growing recognition of the frequent presentation of combined cardiac and renal dysfunction, or "Cardiorenal Syndrome (CRS)", its underlying pathophysiology is not well understood, with a lack of consensus as to its appropriate management.
The main objective of this study is to extend the findings of the applicant's studies in both human and experimental CHF and determine if low dose intravenous (IV) (0.005/Kg/min) administration of BNP in hospitalized decompensated CHF patients with renal dysfunction would improve the renal function. Furthermore, based on our preliminary data, we also sought to assess if PDE V inhibition potentiated these renal enhancing actions.
Hypothesis: Low dose IV infusion of BNP in hospitalized decompensated CHF patients with CRS will enhance renal and humoral functions as compared to standard therapy, which will be further potentiated by PDEV inhibition as evident by:
Increased sodium excretion, Increased creatinine clearance Decreased plasma creatinine and blood urea nitrogen Suppression of the renin-angiotensin-aldosterone system, Increased renal cGMP generation
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| BNP with PDE-V | Active comparator | Drug: BNP and PDE-VBNP (Nesiritide) will be infused starting at 0.0025 g/Kg/min IV for 3 hours, if tolerated increased to 0.005 g/kg/min for 45 hours without bolus with PDEV inhibition, they will also receive Sildenafil 12.5 mg at timepoints 0,12, 24 and 36 hours |
| BNP (Nesiritide) will be infused at 0.005 u/Kg/min IV for 48 h | Active comparator | Drug: BNPBNP (Nesiritide) will be infused at 0.025 ug/Kg/min IV for 3 hours then 0.005ug/kg/min 45 hours without bolus. No PDE-V is given. |
| standard care | No intervention | –Patients randomized to this group will continue to receive therapy at the discretion of the heart failure specialist who is managing the patient (with the exception of BNP and low dose dopamine). Blood and Urine will be collected after the patient has been randomized for 48 hours |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients admitted to St Mary's Hospital, Mayo Clinic Rochester MN with NYHA class III-IV decompensated CHF with renal dysfunction as Calculated creatinine clearance of equal or less than 60 ml/min but greater than 20 ml/min using the Cockcroft-Gault formula.
Key exclusion criteria (14 listed)
- Cause of acute renal dysfunction can be reasonably ascribed to factors other than heart failure or its treatment
- Known intrinsic renal diseases or renal artery stenosis of =>50%
- Patients taking Nitrates within the previous 24 hours
- Patients needing emergency coronary revascularization or those who may have rapidly changing cardiac function (i.e. patients with acute myocardial infarction or shock)
- Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period
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 |
|---|---|---|
| BNP and PDE-VAlso: nesiritide (Natrecor), Viagralow dose BNP 0.025 u/kg/min for 3 hours then 0.005ug/kg/min 45 hours PDE-V 12.5 mg 4 time points | Drug | BNP with PDE-V |
| BNPAlso: Nesiritide (Natrecor)low dose BNP at 0.025 u/kg/min if tolerated then at 0.005 ug/kg/min for 45 hours | Drug | BNP (Nesiritide) will be infused at 0.005 u/Kg/min IV for 48 h |
Primary outcome
The primary endpoint for this aim will be a comparison of the 3 groups for the percent change in creatinine clearance, and blood urea nitrogen from baseline to 48 hours.
Time frame: each blood and urine collections 4 time points
1 secondary outcome
The secondary endpoints for this aim will be a comparison of the 3 groups for the percent change in plasma, sodium excretion, aldosterone, and renal cGMP generation from baseline line to 48 hours
Time frame: each blood and urine collection at 4 time points
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Derived from this study: PubMed 39513267Hubers SA, Benike SL, Johnson BK, McKie PM, Scott C, Chen HH. Renal Effects of Combination Phosphodiesterase V Inhibition and Low-Dose B-Type Natriuretic Peptide in Acute Heart Failure: A Randomized Clinical Trial. Circ Heart Fail. 2024 Dec;17(12):e011761. doi: 10.1161/CIRCHEARTFAILURE.124.011761. Epub 2024 Nov 8.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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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.
Dr Horng H Chen, MD principal investigator
Mayo Clinic
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BNP and PDE-V and BNP in people with Heart Failure and Renal Dysfunction, run by Mayo Clinic.
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 1 inclusion and 14 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: finished, as of the sponsor's last update on 18 Jan 2020. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The primary endpoint for this aim will be a comparison of the 3 groups for the percent change in creatinine clearance, and blood urea nitrogen from baseline to 48 hours. (time frame: each blood and urine collections 4 time points). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00972569, which also lists 1 linked publication.
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 18 Jan 2020; AzTrials last refreshed its copy on 8 Nov 2026.