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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 (Aim 3 BNP/PDEV)

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ClinicalTrials.gov Identifier: NCT00972569
Recruitment Status : Completed
First Posted : September 7, 2009
Last Update Posted : January 18, 2020
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Horng Chen, Mayo Clinic

Tracking Information
First Submitted Date  ICMJE September 3, 2009
First Posted Date  ICMJE September 7, 2009
Last Update Posted Date January 18, 2020
Actual Study Start Date  ICMJE October 2009
Actual Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 4, 2009)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 4, 2009)
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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief 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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Heart Failure
  • Renal Dysfunction
Intervention  ICMJE
  • Drug: BNP and PDE-V
    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
    Other Names:
    • nesiritide (Natrecor)
    • Viagra
  • Drug: BNP
    low dose BNP at 0.025 u/kg/min if tolerated then at 0.005 ug/kg/min for 45 hours
    Other Name: Nesiritide (Natrecor)
Study Arms  ICMJE
  • Active Comparator: BNP with PDE-V
    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
    Intervention: Drug: BNP and PDE-V
  • Active Comparator: BNP (Nesiritide) will be infused at 0.005 u/Kg/min IV for 48 h
    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.
    Intervention: Drug: BNP
  • No Intervention: standard care
    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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 15, 2020)
60
Original Estimated Enrollment  ICMJE
 (submitted: September 4, 2009)
69
Actual Study Completion Date  ICMJE December 2019
Actual Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00972569
Other Study ID Numbers  ICMJE 09-003303
1R01HL08415501A2
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Horng Chen, Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE National Institutes of Health (NIH)
Investigators  ICMJE
Principal Investigator: Dr Horng H Chen, MD Mayo Clinic
PRS Account Mayo Clinic
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP