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

Mayo Clinic

Status and phase

Terminated

Phase 1

Conditions

Renal Dysfunction

Congestive Heart Failure

Treatments

Drug: nesiritide, Sildenafil

Drug: low dose Nesiritide

Study type

Interventional

Funder types

Other

Identifiers

NCT00818701

BNP + PDEVI

08-004797

Details and patient eligibility

About

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.

Full 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.

Enrollment

1 patient

Sex

All

Ages

18 to 90 years old

Volunteers

No 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