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A Study Testing the Effectiveness of Nesiritide in Patients With Acute Decompensated Heart Failure

Phase 3
Completed
Conditions
Heart Decompensation
Interventions
Drug: Nesiritide
Drug: Placebo
Registration Number
NCT00475852
Lead Sponsor
Scios, Inc.
Brief Summary

The purpose of this study is to find out if nesiritide (a human B-type natriuretic peptide/hBNP) as compared to placebo, plus the usual treatment for acute decompensated heart failure, helps to improve breathing difficulties, reduce heart failure readmissions to hospitals, and helps patients live longer.

Detailed Description

Acute Decompensated Heart Failure (ADHF) is the inability of the heart to pump efficiently, which can result in symptoms like shortness of breath at rest or with minimal activity. ADHF is a condition in which the heart cannot perform the necessary circulation of blood through the body. This is a randomized (study medication is assigned by chance), double-blind (neither the patient or the doctor knows whether the patient is assigned to receive study drug or placebo \[does not contain study drug\]), placebo-controlled, parallel group, multicenter study of the effectiveness of nesiritide administered continuously through a vein for a minimum of 24 hours up to a maximum of 7 days. The study hypothesis is that nesiritide given in addition to standard care is superior to placebo given in addition to standard care as measured by relief of breathing difficulties (by patient evaluation utilizing a breathlessness scale) at 6 hours or 24 hours after nesiritide administration, and reduction in rehospitalization due to heart failure and death from study drug administration through Day 30. The study drug (nesiritide) or placebo dose being studied is 0.010 mcg/kg/min with or without a 2 mcg/kg initial bolus (one time injection) of nesiritide. Patient safety will be monitored throughout the study through physical exams, vital signs (heart rate, blood pressure, respiratory rate, and temperature), blood tests, and side effects. The patients assigned to the nesiritide group will receive a continuous intravenous (into a vein) infusion at 0.010 mcg/kg/min of nesiritide with or without a 2 mcg/kg bolus (one time injection). The patients assigned to the placebo group will receive matching placebo bolus and infusion. The bolus is given over one minute and the continuous infusion is given for at least 24 hours and up to 7 days.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
7141
Inclusion Criteria

Hospitalized for the management of acute decompensated heart failure (ADHF) or diagnosed with ADHF within 48 hours after being hospitalized for another reason; Diagnosis of ADHF is defined as dyspnea (difficulty breathing) at rest or dyspnea with minimal activity.

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Exclusion Criteria

At high risk for hypotension (low blood pressure); Acute coronary syndrome as primary diagnosis; History of cardiac valvular stenosis, restrictive cardiomyopathy, hypertrophic cardiomyopathy, or pericardial tamponade; Previous enrollment in a nesiritide study; Persistent, uncontrolled hypertension (SBP [systolic blood pressure] >180 mmHg).

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
001NesiritideNesiritide 0.01 mcg/kg/min intravenous (IV) infusion (with or without 2 mcg/kg bolus) for 24 to 168 hours (hrs)
002PlaceboPlacebo matching placebo infusion:0.01 mcg/kg/min IV infusion (with or without 2 mcg/kg bolus) for 24 to 168 hrs
Primary Outcome Measures
NameTimeMethod
Composite of Rehospitalization Due to Heart Failure and All-Cause MortalityRandomization to Day 30
Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug6 hours after initiation of study drug

Dyspnea symptoms were measured by patient self-assessed Likert scale at 6 hours after study drug initiation.The Likert scale is a 7-point ordinal categorical scale (the 7 categories are markedly better, moderately better, minimally better, unchanged, minimally worse, moderately worse, and markedly worse.)

Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug24 hours after study drug initiation

Dyspnea symptoms were measured by patient self-assessed Likert scale at 24 hours after study drug initiation. The Likert scale is a 7-point ordinal categorical scale (the 7 categories are markedly better, moderately better, minimally better, unchanged, minimally worse, moderately worse, and markedly worse.)

Secondary Outcome Measures
NameTimeMethod
Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug24 hours after study drug initiation

Overall well-being was measured by patient self-assessed Likert scale at 24 hours after study drug initiation. The Likert scale is a 7-point ordinal categorical scale (the 7 categories are markedly better, moderately better, minimally better, unchanged, minimally worse, moderately worse, and markedly worse.)

Composite of Persistent or Worsening Heart Failure and All-Cause MortalityRandomization to hospital discharge (up to Day 30)

Clinical manifestations of worsening or persistent decompensated heart failure were defined by at least one of the following: new, persistent or worsening: dyspnea, orthopnea, paroxysmal nocturnal dyspnea, edema, pulmonary basilar rales/crackles, jugular venous distension, renal hypoperfusion with no other apparent cause, or radiologic evidence of worsening heart failure. And was also defined by a new therapy specifically for the treatment of worsening or persistent decompensated heart failure.

Number of Days Alive and Outside the HospitalRandomization to Day 30
Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug6 hours after study drug initiation

Overall well-being was measured by patient self-assessed Likert scale at 6 hours after study drug initiation. The Likert scale is a 7-point ordinal categorical scale (the 7 categories are markedly better, moderately better, minimally better, unchanged, minimally worse, moderately worse, and markedly worse.)

Composite of Cardiovascular Rehospitalization and Cardiovascular MortalityRandomization to Day 30
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