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)

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Horng Chen, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00972569
First received: September 3, 2009
Last updated: May 30, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Heart Failure
Renal Dysfunction
Drug: BNP and PDE-V
Drug: BNP
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 69
Study Start Date: October 2009
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
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.
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)
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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00972569

Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Dr Horng H Chen, MD Mayo Clinic
  More Information

No publications provided

Responsible Party: Horng Chen, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00972569     History of Changes
Other Study ID Numbers: 09-003303, 1R01HL08415501A2
Study First Received: September 3, 2009
Last Updated: May 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
BNP with or without PDE-V in heart failure

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Natriuretic Peptide, Brain
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 23, 2014