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

Sponsored by:	Mayo Clinic
Information provided by:	Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00818701

Purpose

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	Intervention	Phase
Congestive Heart Failure Renal Dysfunction	Drug: low dose Nesiritide Drug: nesiritide, Sildenafil	Phase I

MedlinePlus related topics: Heart Failure

Drug Information available for: Sildenafil citrate Sildenafil Nesiritide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Basic Science, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Crossover Assignment, Pharmacokinetics/Dynamics Study
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

Further study details as provided by Mayo Clinic:

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.) [ Time Frame: prospective ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

We also want to characterize both plasma and urinary humoral profile in these patients. [ Time Frame: prospective ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	February 2009
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: low dose BNP alone: Placebo Comparator low dose BNP with placebo	Drug: low dose Nesiritide Nesiritide infusion 0.005ug/kg/min
2: low dose BNP + PDEVI: Active Comparator low dose BNpo + PDEVI	Drug: nesiritide, Sildenafil Nesiritide 0.005ug/kg/min Sildenafil 50 mg

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.

Eligibility

Ages Eligible for Study:	18 Years to 90 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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:
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00818701

Locations

United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55902

Sponsors and Collaborators

Mayo Clinic

Investigators

Principal Investigator:

Horng H Chen, MD

Mayo Clinic

More Information

Responsible Party:	Mayo Clinc ( Dr Horng H. Chen )
Study ID Numbers:	08-004797, BNP + PDEVI
Study First Received:	January 6, 2009
Last Updated:	January 7, 2009
ClinicalTrials.gov Identifier:	NCT00818701
Health Authority:	United States: Institutional Review Board

Keywords provided by Mayo Clinic:

Congestive Heart Failure
Congestive Heart Failure with a NYHF Class 2-3
Ejection Fraction of 35 or less

Study placed in the following topic categories:

Natriuretic Peptide, Brain
Heart Failure
Heart Diseases
Sildenafil

Additional relevant MeSH terms:

Vasodilator Agents
Phosphodiesterase Inhibitors
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Therapeutic Uses

Physiological Effects of Drugs
Enzyme Inhibitors
Cardiovascular Diseases
Cardiovascular Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009