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

This study has been terminated.
(started a NIH study that is competing for same subjects)
Sponsor:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00818701
First received: January 6, 2009
Last updated: September 23, 2010
Last verified: September 2010
History of Changes
  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 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

MedlinePlus related topics: Heart Failure
U.S. FDA Resources

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 ]

Enrollment: 1
Study Start Date: February 2009
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1: low dose BNP alone
low dose BNP with placebo
 Drug: low dose Nesiritide
Nesiritide infusion 0.005ug/kg/min
Other Name: 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

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
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Horng H Chen, MD Mayo Clinic
  More Information

No publications provided

Responsible Party: Dr Horng H. Chen, Mayo Clinc
ClinicalTrials.gov Identifier: NCT00818701     History of Changes
Other Study ID Numbers: 08-004797, BNP + PDEVI
Study First Received: January 6, 2009
Last Updated: September 23, 2010
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

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Natriuretic Peptide, Brain
Sildenafil
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
 Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 18, 2013