search
Back to results

Study of Low Dose Nesiritide With or Without Sildenafil in Congestive Heart Failure Patients With Renal Dysfunction (BNP+PDEVI)

Primary Purpose

Congestive Heart Failure, Renal Dysfunction

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
low dose Nesiritide
nesiritide, Sildenafil
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Congestive Heart Failure focused on measuring Congestive Heart Failure, Congestive Heart Failure with a NYHF Class 2-3, Ejection Fraction of 35 or less

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Left ventricular ejection fraction 35% assessed by echocardiography, nuclear scan or left ventriculogram within the past 2 years

  • Stable (NYHA) class II and III symptoms as defined by:

    1. no change in NYHA symptoms over the past 3 months;
    2. on stable doses of ACE inhibitor and beta blocker for one month;
    3. no episode of decompensated CHF over the past 3 months.
  • Calculated creatinine clearance of equal or less than 60 ml/min and greater than 30 ml/min, using the Cockcroft-Gault formula assessed within the past 12 months

Exclusion Criteria:

  • Nitrates or alpha blockers
  • Prior diagnosis of intrinsic renal diseases including renal artery stenosis of > 50%
  • Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period
  • Hospitalization for decompensated CHF during the past 3 months
  • Myocardial infarction within 3 months of screening
  • Unstable angina within 3 months of screening or any evidence of myocardial ischemia
  • Significant valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis
  • Severe congenital heart diseases
  • Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening
  • Second or third degree heart block without a permanent cardiac pacemaker
  • Stroke within 3 months of screening or other evidence of significantly compromised CNS perfusion
  • Serum sodium of < 125 mEq/dL or > 150 mEq/dL
  • Serum potassium of < 3.5 mEq/dL or > 5.7 mEq/dL
  • Hemoglobin < 10 gm/dl
  • Other acute or chronic medical conditions or laboratory abnormality which may increase the risks associated with study participation or may interfere with interpretation of the data
  • Received an investigational drug within 1 month prior to dosing
  • Patients with an allergy to iodine.
  • Female subject who is pregnant or breastfeeding

Sites / Locations

  • Mayo Clinic
  • Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

1: low dose BNP alone

2: low dose BNP + PDEVI

Arm Description

low dose BNP with placebo

low dose BNpo + PDEVI

Outcomes

Primary Outcome Measures

To determine the efficacy of low dose BNP alone vs low dose BNP + PDE V inhibition in improving renal function in patients with CHF and renal dysfunction. (Calculated creatinine clearance = or < than 60 ml/min and > 30 ml/min, within 12 months.)

Secondary Outcome Measures

We also want to characterize both plasma and urinary humoral profile in these patients.

Full Information

First Posted
January 6, 2009
Last Updated
September 23, 2010
Sponsor
Mayo Clinic
search

1. Study Identification

Unique Protocol Identification Number
NCT00818701
Brief Title
Study of Low Dose Nesiritide With or Without Sildenafil in Congestive Heart Failure Patients With Renal Dysfunction
Acronym
BNP+PDEVI
Official Title
A Randomized, Double Blinded Placebo Controlled Cross-over Study of Low Dose B-type Natriuretic Peptide (Nesiritide) With or Without Concomitant Phosphodiesterase V (PDE V) Inhibition(Sildenafil) in Congestive Heart Failure Patients With Renal Dysfunction
Study Type
Interventional

2. Study Status

Record Verification Date
September 2010
Overall Recruitment Status
Terminated
Why Stopped
started a NIH study that is competing for same subjects
Study Start Date
February 2009 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
August 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Mayo Clinic

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of the study is to show that low dose recombinant BNP coupled with phosphodiesterase V inhibition will improve renal dysfunction and promote relief of volume overload in patinets with acute decompensated heart failure complicated by the cardiorenal syndrome.
Detailed Description
Renal dysfunction is a common comorbidity, as well as a common and progressive complication, of heart failure (HF). Increasingly, the clinical syndrome of HF is one of "cardiorenal" failure owing to the frequent presentation of combined cardiac and renal dysfunction. Recent studies have established the prognostic importance of renal dysfunction in patients with chronic HF. An analysis of the patients in the second prospective randomized study of Ibopamine on mortality and efficacy (PRIME) by Hillege et al1 demonstrated that estimated glomerular filtration rate (GFR) is the most powerful predictor of mortality, exceeding functional status and ejection fraction (EF). In an ongoing prospective study, we are assessing the neurohumoral and renal hemodynamic profile of hospitalized patients with ADHF who do or do not develop the CRS. Our preliminary findings suggest that indeed the combination of pronounced activation of renin-angiotensin-aldosterone system (RAAS), decreased renal perfusion pressure and importantly, a relative deficiency of the natriuretic peptides (despite marked volume overload) predisposes to the development of CRS.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congestive Heart Failure, Renal Dysfunction
Keywords
Congestive Heart Failure, Congestive Heart Failure with a NYHF Class 2-3, Ejection Fraction of 35 or less

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1: low dose BNP alone
Arm Type
Placebo Comparator
Arm Description
low dose BNP with placebo
Arm Title
2: low dose BNP + PDEVI
Arm Type
Active Comparator
Arm Description
low dose BNpo + PDEVI
Intervention Type
Drug
Intervention Name(s)
low dose Nesiritide
Other Intervention Name(s)
Natracor
Intervention Description
Nesiritide infusion 0.005ug/kg/min
Intervention Type
Drug
Intervention Name(s)
nesiritide, Sildenafil
Other Intervention Name(s)
Natrecor, Viagra
Intervention Description
Nesiritide 0.005ug/kg/min Sildenafil 50 mg
Primary Outcome Measure Information:
Title
To determine the efficacy of low dose BNP alone vs low dose BNP + PDE V inhibition in improving renal function in patients with CHF and renal dysfunction. (Calculated creatinine clearance = or < than 60 ml/min and > 30 ml/min, within 12 months.)
Time Frame
prospective
Secondary Outcome Measure Information:
Title
We also want to characterize both plasma and urinary humoral profile in these patients.
Time Frame
prospective

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Left ventricular ejection fraction 35% assessed by echocardiography, nuclear scan or left ventriculogram within the past 2 years Stable (NYHA) class II and III symptoms as defined by: no change in NYHA symptoms over the past 3 months; on stable doses of ACE inhibitor and beta blocker for one month; no episode of decompensated CHF over the past 3 months. Calculated creatinine clearance of equal or less than 60 ml/min and greater than 30 ml/min, using the Cockcroft-Gault formula assessed within the past 12 months Exclusion Criteria: Nitrates or alpha blockers Prior diagnosis of intrinsic renal diseases including renal artery stenosis of > 50% Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period Hospitalization for decompensated CHF during the past 3 months Myocardial infarction within 3 months of screening Unstable angina within 3 months of screening or any evidence of myocardial ischemia Significant valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis Severe congenital heart diseases Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening Second or third degree heart block without a permanent cardiac pacemaker Stroke within 3 months of screening or other evidence of significantly compromised CNS perfusion Serum sodium of < 125 mEq/dL or > 150 mEq/dL Serum potassium of < 3.5 mEq/dL or > 5.7 mEq/dL Hemoglobin < 10 gm/dl Other acute or chronic medical conditions or laboratory abnormality which may increase the risks associated with study participation or may interfere with interpretation of the data Received an investigational drug within 1 month prior to dosing Patients with an allergy to iodine. Female subject who is pregnant or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Horng H Chen, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55902
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Study of Low Dose Nesiritide With or Without Sildenafil in Congestive Heart Failure Patients With Renal Dysfunction

We'll reach out to this number within 24 hrs