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

Sponsor

Mayo Clinic (Other)

Overall Status

Terminated

CT.gov ID

NCT00818701

Collaborator

(none)

Enrollment

Locations

Arms

17.9

Duration (Months)

0.5

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Congestive Heart Failure Renal Dysfunction	Drug: low dose Nesiritide Drug: nesiritide, Sildenafil	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Basic Science

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 Start Date :

Feb 1, 2009

Actual Primary Completion Date :

Aug 1, 2010

Actual Study Completion Date :

Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1: low dose BNP alone low dose BNP with placebo	Drug: low dose Nesiritide Nesiritide infusion 0.005ug/kg/min Other Names: Natracor
Active Comparator: 2: low dose BNP + PDEVI low dose BNpo + PDEVI	Drug: nesiritide, Sildenafil Nesiritide 0.005ug/kg/min Sildenafil 50 mg Other Names: Natrecor Viagra

Arm

Intervention/Treatment

Placebo Comparator: 1: low dose BNP alone

low dose BNP with placebo

Drug: low dose Nesiritide

Nesiritide infusion 0.005ug/kg/min

Other Names:

Natracor

Active Comparator: 2: low dose BNP + PDEVI

low dose BNpo + PDEVI

Drug: nesiritide, Sildenafil

Nesiritide 0.005ug/kg/min Sildenafil 50 mg

Other Names:

Natrecor

Viagra

Outcome Measures

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.) [prospective]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts 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:

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