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

Heart Decompensation Clinical Trial

Official title:

Double-Blind, Placebo-Controlled, Multicenter Acute Study of Clinical Effectiveness of Nesiritide in Subjects With Decompensated Heart Failure (ASCEND-HF)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00475852
• Other study ID #: CR013954
• Secondary ID: ASCEND-HFA093NAT
• Status: Completed
• Phase: Phase 3
• First received: May 18, 2007
• Last updated: March 1, 2013
• Start date: May 2007
• Est. completion date: March 2011

Study information

• Verified date: March 2013
• Source: Scios, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationChina: Food and Drug AdministrationLithuania: State Medicine Control Agency - Ministry of HealthRomania: National Medicines AgencySweden: Medical Products AgencyUkraine: State Pharmacological Center - Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 7141
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Decompensation
• Heart Failure

Intervention

Drug:
• Nesiritide
0.01 mcg/kg/min IV infusion (with or without 2 mcg/kg bolus) for 24 to 168 hrs
• Placebo
matching placebo infusion:0.01 mcg/kg/min IV infusion (with or without 2 mcg/kg bolus) for 24 to 168 hrs

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Scios, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Colombia,  France,  Germany,  Greece,  India,  Israel,  Korea, Republic of,  Lithuania,  Malaysia,  Mexico,  Netherlands,  New Zealand,  Norway,  Poland,  Russian Federation,  Singapore,  Sweden,  Taiwan,  Thailand,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	All-Cause Mortality Through Day 30	All deaths were adjudicated by an independent Clinical Events Committee.	Randomization to Day 30	Yes
Other	All-Cause Mortality Through Day 180	All deaths were adjudicated by an independent Clinical Events Committee.	Randomization to Day 180	Yes
Other	Cardiovascular Mortality Through Day 30	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.	Randomization to Day 30	Yes
Other	Number of Patients With Renal Impairment	Renal impairment was defined as a greater than 25% decrease from baseline in the Modification of Diet in Renal Disease calculated glomerular filtration rate.	Study drug initiation to Day 30	Yes
Primary	Composite of Rehospitalization Due to Heart Failure and All-Cause Mortality		Randomization to Day 30	Yes
Primary	Dyspnea Self-Assessment at 6 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.)	6 hours after initiation of study drug	Yes
Primary	Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug	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.)	24 hours after study drug initiation	Yes
Secondary	Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug	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.)	6 hours after study drug initiation	Yes
Secondary	Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug	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.)	24 hours after study drug initiation	Yes
Secondary	Composite of Persistent or Worsening Heart Failure and All-Cause Mortality	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.	Randomization to hospital discharge (up to Day 30)	Yes
Secondary	Number of Days Alive and Outside the Hospital		Randomization to Day 30	Yes
Secondary	Composite of Cardiovascular Rehospitalization and Cardiovascular Mortality		Randomization to Day 30	Yes

External Links

•   A study testing the effectiveness of Nesiritide in Patients with Acute Decompensated Heart Failure