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

NCT00505791 | Withdrawn Phase 4

• 2 other identifiers: 0120050150IRB # 0120050150
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Failure, Congestive; Dyspnea; Pulmonary Edema

Keywords

Acute decompensated heart failure; Normal left ventricular ejection fraction; Vasodilator therapy

Outcome Measures

Primary Outcomes (1)

• The primary endpoint of this study will be an absolute reduction in brain natriuretic peptide (BNP) three hours after discontinuation of the study drug.

  Three hours after discontinuation of the study drug

Secondary Outcomes (4)

• All cause in-hospital mortality

  30 days post-randomization

• Physician and patient global score at 24 hours

  30 days post-randomization

• Twenty-four hour urine output after start of study drug infusion

  30 days post-randomization

• Weight change at 24 hours after start of study drug infusion

  30 days post-randomization

Study Arms (2)

Sugar pill

PLACEBO COMPARATOR

Lactose, NF (monohydrate)

Drug: Nesiritide

Nesiritide

ACTIVE COMPARATOR

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

Interventions

Nesiritide DRUG

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.

Also known as: Natrecor

Nesiritide; Sugar pill

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Medicine and Dentistry of New Jersey: lead
• Scios, Inc.: collaborator

Study Sites (1)

University of Medicine and Dentistry of New Jersey/ New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

Related Publications (6)

• Polanczyk CA, Rohde LE, Dec GW, DiSalvo T. Ten-year trends in hospital care for congestive heart failure: improved outcomes and increased use of resources. Arch Intern Med. 2000 Feb 14;160(3):325-32. doi: 10.1001/archinte.160.3.325.

  PMID: 10668834 BACKGROUND

• Publication Committee for the VMAC Investigators (Vasodilatation in the Management of Acute CHF). Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA. 2002 Mar 27;287(12):1531-40. doi: 10.1001/jama.287.12.1531.

  PMID: 11911755 BACKGROUND

• Francis GS, Siegel RM, Goldsmith SR, Olivari MT, Levine TB, Cohn JN. Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure. Activation of the neurohumoral axis. Ann Intern Med. 1985 Jul;103(1):1-6. doi: 10.7326/0003-4819-103-1-1.

  PMID: 2860833 BACKGROUND

• Weinfeld MS, Chertow GM, Stevenson LW. Aggravated renal dysfunction during intensive therapy for advanced chronic heart failure. Am Heart J. 1999 Aug;138(2 Pt 1):285-90. doi: 10.1016/s0002-8703(99)70113-4.

  PMID: 10426840 BACKGROUND

• Mueller C, Scholer A, Laule-Kilian K, Martina B, Schindler C, Buser P, Pfisterer M, Perruchoud AP. Use of B-type natriuretic peptide in the evaluation and management of acute dyspnea. N Engl J Med. 2004 Feb 12;350(7):647-54. doi: 10.1056/NEJMoa031681.

  PMID: 14960741 BACKGROUND

• Butler J, Emerman C, Peacock WF, Mathur VS, Young JB; VMAC study investigators. The efficacy and safety of B-type natriuretic peptide (nesiritide) in patients with renal insufficiency and acutely decompensated congestive heart failure. Nephrol Dial Transplant. 2004 Feb;19(2):391-9. doi: 10.1093/ndt/gfg558.

  PMID: 14736964 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Dyspnea; Pulmonary Edema

Interventions

Natriuretic Peptide, Brain

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lung Diseases

Intervention Hierarchy (Ancestors)

Natriuretic Peptides; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Study Officials

• Marc Klapholz, MD

  University of Medicine and Dentistry of New Jersey/ New Jersey Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2007
• First Posted: July 23, 2007
• Study Start: August 1, 2007
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: November 11, 2015

Record last verified: 2015-11

Locations

US (1)