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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Scios, Inc.
ClinicalTrials.gov Identifier:
NCT00475852
First received: May 18, 2007
Last updated: March 1, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Heart Decompensation
Drug: Nesiritide
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-Blind, Placebo-Controlled, Multicenter Acute Study of Clinical Effectiveness of Nesiritide in Subjects With Decompensated Heart Failure (ASCEND-HF)

Resource links provided by NLM:


Further study details as provided by Scios, Inc.:

Primary Outcome Measures:
  • Composite of Rehospitalization Due to Heart Failure and All-Cause Mortality [ Time Frame: Randomization to Day 30 ] [ Designated as safety issue: Yes ]
  • Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug [ Time Frame: 6 hours after initiation of study drug ] [ Designated as safety issue: Yes ]
    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 Drug [ Time Frame: 24 hours after study drug initiation ] [ Designated as safety issue: Yes ]
    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:
  • Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug [ Time Frame: 6 hours after study drug initiation ] [ Designated as safety issue: Yes ]
    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.)

  • Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug [ Time Frame: 24 hours after study drug initiation ] [ Designated as safety issue: Yes ]
    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 Mortality [ Time Frame: Randomization to hospital discharge (up to Day 30) ] [ Designated as safety issue: Yes ]
    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 Hospital [ Time Frame: Randomization to Day 30 ] [ Designated as safety issue: Yes ]
  • Composite of Cardiovascular Rehospitalization and Cardiovascular Mortality [ Time Frame: Randomization to Day 30 ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • All-Cause Mortality Through Day 30 [ Time Frame: Randomization to Day 30 ] [ Designated as safety issue: Yes ]
    All deaths were adjudicated by an independent Clinical Events Committee.

  • All-Cause Mortality Through Day 180 [ Time Frame: Randomization to Day 180 ] [ Designated as safety issue: Yes ]
    All deaths were adjudicated by an independent Clinical Events Committee.

  • Cardiovascular Mortality Through Day 30 [ Time Frame: Randomization to Day 30 ] [ Designated as safety issue: Yes ]
    All deaths were adjudicated by an independent Clinical Events Committee (CEC) and the cardiovascular deaths were classified by the CEC based on the primary causes.

  • Number of Patients With Renal Impairment [ Time Frame: Study drug initiation to Day 30 ] [ Designated as safety issue: Yes ]
    Renal impairment was defined as a greater than 25% decrease from baseline in the Modification of Diet in Renal Disease calculated glomerular filtration rate.


Enrollment: 7141
Study Start Date: May 2007
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
Nesiritide 0.01 mcg/kg/min intravenous (IV) infusion (with or without 2 mcg/kg bolus) for 24 to 168 hours (hrs)
Drug: Nesiritide
0.01 mcg/kg/min IV infusion (with or without 2 mcg/kg bolus) for 24 to 168 hrs
Placebo Comparator: 002
Placebo matching placebo infusion:0.01 mcg/kg/min IV infusion (with or without 2 mcg/kg bolus) for 24 to 168 hrs
Drug: Placebo
matching placebo infusion:0.01 mcg/kg/min IV infusion (with or without 2 mcg/kg bolus) for 24 to 168 hrs

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.

  Eligibility

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

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.

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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Please refer to this study by its ClinicalTrials.gov identifier: NCT00475852

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Sponsors and Collaborators
Scios, Inc.
Investigators
Study Director: Scios, Inc. Clinical Trial Scios, Inc.
  More Information

Additional Information:
No publications provided by Scios, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
O'Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V, Heizer GM, Komajda M, Massie BM, McMurray JJ, Nieminen MS, Reist CJ, Rouleau JL, Swedberg K, Adams KF Jr, Anker SD, Atar D, Battler A, Botero R, Bohidar NR, Butler J, Clausell N, Corbalán R, Costanzo MR, Dahlstrom U, Deckelbaum LI, Diaz R, Dunlap ME, Ezekowitz JA, Feldman D, Felker GM, Fonarow GC, Gennevois D, Gottlieb SS, Hill JA, Hollander JE, Howlett JG, Hudson MP, Kociol RD, Krum H, Laucevicius A, Levy WC, Méndez GF, Metra M, Mittal S, Oh BH, Pereira NL, Ponikowski P, Tang WH, Tanomsup S, Teerlink JR, Triposkiadis F, Troughton RW, Voors AA, Whellan DJ, Zannad F, Califf RM. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med. 2011 Jul 7;365(1):32-43. doi: 10.1056/NEJMoa1100171. Erratum in: N Engl J Med. 2011 Aug 25;365(8):773. Wilson, W H [corrected to Tang, W H W].

Responsible Party: Scios, Inc.
ClinicalTrials.gov Identifier: NCT00475852     History of Changes
Other Study ID Numbers: CR013954, ASCEND-HF, A093, NATRECORAHF3002
Study First Received: May 18, 2007
Results First Received: September 27, 2011
Last Updated: March 1, 2013
Health Authority: United States: Food and Drug Administration
China: Food and Drug Administration
Lithuania: State Medicine Control Agency - Ministry of Health
Romania: National Medicines Agency
Sweden: Medical Products Agency
Ukraine: State Pharmacological Center - Ministry of Health

Keywords provided by Scios, Inc.:
Heart Decompensation
Dyspnea
Heart failure
Nesiritide
Decompensated
ADHF

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Natriuretic Peptide, Brain
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014