Double Blind Randomized Placebo Controlled Trial of Natrecor in Acute Decompensated Heart Failure With Normal EF

This study has been withdrawn prior to enrollment.
(Unable to enroll patients)
Sponsor:
Collaborator:
Scios, Inc.
Information provided by (Responsible Party):
Rutgers, The State University of New Jersey ( University of Medicine and Dentistry New Jersey )
ClinicalTrials.gov Identifier:
NCT00505791
First received: July 19, 2007
Last updated: September 20, 2013
Last verified: September 2013
  Purpose

Heart failure (HF) is a disease that is caused by a reduced heart muscle function. Reduced heart muscle function can occur as a consequence of reduced pumping activity from a weak heart muscle or because of a stiff heart muscle. This study is looking at the effectiveness of Natrecor (nesiritide) in patients that require hospitalization due to worsening heart failure as a result of a stiff or thickened heart muscle. Natrecor is a man-made version of a protein that my body makes on its own and has been approved for the treatment of patients requiring hospital admission for heart failure and have shortness of breath at rest or with minimal activity.

Natrecor has shown to lower the pressures in the heart and decreases the congestion in the lungs. This study is being done to see if the addition of a Natrecor to standard medical therapy for HF will improve symptoms faster or more completely than giving only the standard treatment for CHF.


Condition Intervention Phase
Heart Failure, Congestive
Dyspnea
Pulmonary Edema
Drug: Nesiritide
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double Blind Randomized Placebo Controlled Trial of Natrecor in Patients Hospitalized for Decompensated Heart Failure in the Presence of a Normal Left Ventricular Ejection Fraction

Resource links provided by NLM:


Further study details as provided by Rutgers, The State University of New Jersey:

Primary Outcome Measures:
  • The primary endpoint of this study will be an absolute reduction in brain natriuretic peptide (BNP) three hours after discontinuation of the study drug. [ Time Frame: Three hours after discontinuation of the study drug ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • All cause in-hospital mortality [ Time Frame: 30 days post-randomization ] [ Designated as safety issue: Yes ]
  • Physician and patient global score at 24 hours [ Time Frame: 30 days post-randomization ] [ Designated as safety issue: Yes ]
  • Twenty-four hour urine output after start of study drug infusion [ Time Frame: 30 days post-randomization ] [ Designated as safety issue: Yes ]
  • Weight change at 24 hours after start of study drug infusion [ Time Frame: 30 days post-randomization ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: August 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Sugar pill
Lactose, NF (monohydrate)
Active Comparator: Nesiritide
Natrecor (nesiritide) is a commercially available B-type natriuretic peptide which is indicated for intravenous treatment of patients with acutely decompensated congestive heart failure who have dyspnea at rest or with minimal activity.
Drug: Nesiritide
Study drug will be administered for 24 hours. Study drug will be initiated with a 2-µg/kg loading bolus followed by .01-µg/kg/min infusion. This may be increased at a rate of .005-µg/kg/min. every 3 hours until maximum dose of .03-µg/kg/min. Any increase in the infusion rate will be preceded by a 1-µg/kg bolus and increases in infusion rates will be permitted only in patients who have a systolic blood pressure > 100 mmHg.
Other Name: Natrecor

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients greater than 18 years of age
  • Admission to the ED for congestive heart failure requiring IV diuretics and hospitalization
  • Chest X-ray evidence of pulmonary congestion (pleural effusion will not suffice).
  • Physical evidence of volume overload i.e. rales or edema at time of randomization.
  • Normal left ventricular ejection fraction (EF >50%) on echocardiography after presentation to the ER.
  • Patients must be able to provide informed consent.

Exclusion Criteria:

  • Acute coronary syndrome with evidence of active ischemia as evident by acute ST segment or T wave changes or initial cardiac enzymes that demonstrate myocardial necrosis or requiring IV nitroglycerin for treatment.
  • Hemodynamically unstable patients that require invasive monitoring or mechanical ventilation.
  • Cardiogenic shock, volume depletion, or any other clinical condition that would contraindicate the administration of IV diuretics, ACE inhibitors, or an IV agent with potent vasodilating properties.
  • Systolic blood pressure >220mmHg or diastolic blood pressure >110mHg.
  • Systolic blood pressure consistently <90 mmHg.
  • Tachyarrhythmia (HR>120).
  • Bradyarrythmia (HR < 50).
  • Myocarditis.
  • Hypertrophic obstructive cardiomyopathy.
  • Restrictive or infiltrative cardiomyopathy including amyloid or sarcoid.
  • Constrictive cardiomyopathy.
  • Primary right sided heart failure or severe pulmonary hypertension (pulmonary artery pressure > 60mmHg).
  • Significant aortic or mitral valve stenosis (Aortic Valve Area < 1.0cm2, Mitral Valve Area < 1.5 cm2 ).
  • Aortic or mitral insufficiency ≥ 3+.
  • Malfunctioning artificial valve.
  • Uncorrected congenital heart disease.
  • Concomitant administration of IV Dobutamine, or other IV vasoactive medications from 2 hours before the start of the study drug until 3 hours after the start of the study drug;
  • Administration of IV Nitroglycerin or IV Milrinone.
  • Concomitant administration of oral ACE inhibitor medication from 2 hours before the start of the study drug until 30 minutes after the start of the study drug.
  • Severe COPD/Asthma as assessed by clinical criteria, prior PFT's or if the patient requires chronic oral steroid treatment.
  • Other significant pulmonary disease that causes significant SOB/DOE i.e. pneumoconiosis etc.
  • Patients with creatinine > 3.0 mg/dl.
  • Patients with a serum potassium level < 3.5, >5.5 mmol/l.
  • Anemia with a Hob < 9 g/dl.
  • Acute neurological event.
  • Known allergic reaction or contraindication to Natrecor or furosemide.
  • Pregnancy or suspected pregnancy.
  • Patients with a history of ETOH abuse or other illicit drug abuse.
  • Patients with active liver, hematologic, gastrointestinal, immunologic, endocrine, metabolic, central nervous system or other medical condition disease which in the opinion of the investigator may adversely effect the safety and efficacy of the study drug or the lifespan of the patient.
  • Therapy with an investigational drug.
  • Unwillingness or inability to comply with study requirements including the 30-day follow-up period.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00505791

Locations
United States, New Jersey
University of Medicine and Dentistry of New Jersey/ New Jersey Medical School
Newark, New Jersey, United States, 07103
Sponsors and Collaborators
University of Medicine and Dentistry New Jersey
Scios, Inc.
Investigators
Principal Investigator: Marc Klapholz, MD University of Medicine and Dentistry of New Jersey/ New Jersey Medical School
  More Information

Publications:
Responsible Party: Rutgers, The State University of New Jersey ( University of Medicine and Dentistry New Jersey )
ClinicalTrials.gov Identifier: NCT00505791     History of Changes
Other Study ID Numbers: 0120050150, IRB # 0120050150
Study First Received: July 19, 2007
Last Updated: September 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Rutgers, The State University of New Jersey:
Acute decompensated heart failure
Normal left ventricular ejection fraction
Vasodilator therapy

Additional relevant MeSH terms:
Dyspnea
Edema
Heart Failure
Pulmonary Edema
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Heart Diseases
Cardiovascular Diseases
Lung Diseases
Natriuretic Peptide, Brain
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014