Heart Decompensation
Conditions
Keywords
Heart Decompensation, Dyspnea, Heart failure, Nesiritide, Decompensated, ADHF
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.
Interventions
DRUGNesiritide
0.01 mcg/kg/min IV infusion (with or without 2 mcg/kg bolus) for 24 to 168 hrs
DRUGPlacebo
matching placebo infusion:0.01 mcg/kg/min IV infusion (with or without 2 mcg/kg bolus) for 24 to 168 hrs
Sponsors
Scios, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of Rehospitalization Due to Heart Failure and All-Cause Mortality | Randomization to Day 30 | — |
| Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug | 24 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.) |
| Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug | 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.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite of Persistent or Worsening Heart Failure and All-Cause Mortality | Randomization 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. |
| Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug | 6 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.) |
| Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug | 24 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.) |
| Number of Days Alive and Outside the Hospital | Randomization to Day 30 | — |
| Composite of Cardiovascular Rehospitalization and Cardiovascular Mortality | Randomization to Day 30 | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| All-Cause Mortality Through Day 180 | Randomization to Day 180 | All deaths were adjudicated by an independent Clinical Events Committee. |
| Number of Patients With Renal Impairment | Study drug initiation to Day 30 | Renal impairment was defined as a greater than 25% decrease from baseline in the Modification of Diet in Renal Disease calculated glomerular filtration rate. |
| All-Cause Mortality Through Day 30 | Randomization to Day 30 | All deaths were adjudicated by an independent Clinical Events Committee. |
| Cardiovascular Mortality Through Day 30 | Randomization to 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. |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Chile, China, Colombia, France, Germany, Greece, India, Israel, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Norway, Poland, Russia, Singapore, South Korea, Sweden, Taiwan, Thailand, Ukraine, United States
Participant flow
Pre-assignment details
Double-Blind, Placebo-Controlled, Multicenter Acute Study of Clinical Effectiveness of Nesiritide in Subjects With Decompensated Heart Failure (ASCEND-HF)
Participants by arm
| Arm | Count |
|---|---|
| Nesiritide 0.01 mcg/kg/min IV infusion (with or without 2 mcg/kg bolus) for 24 to 168 hrs | 3,564 |
| Placebo Matching placebo infusion:0.01 mcg/kg/min IV infusion (with or without 2 mcg/kg bolus) for 24 to 168 hrs | 3,577 |
| Total | 7,141 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 444 | 456 |
| Overall Study | Lost to Follow-up | 54 | 68 |
| Overall Study | Withdrawal by Subject | 19 | 24 |
Baseline characteristics
| Characteristic | Nesiritide | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 4 Participants | 2 Participants | 6 Participants |
| Age, Categorical >=65 years | 1988 Participants | 1978 Participants | 3966 Participants |
| Age, Categorical Between 18 and 65 years | 1572 Participants | 1597 Participants | 3169 Participants |
| Age Continuous | 65.5 years STANDARD_DEVIATION 14.09 | 65.4 years STANDARD_DEVIATION 14.2 | 65.5 years STANDARD_DEVIATION 14.14 |
| Age, Customized <=64 | 1576 participants | 1599 participants | 3175 participants |
| Age, Customized 65-74 | 938 participants | 901 participants | 1839 participants |
| Age, Customized >=75 | 1050 participants | 1077 participants | 2127 participants |
| Baseline BMI | 28.9 kg/cm2 STANDARD_DEVIATION 7.86 | 29.1 kg/cm2 STANDARD_DEVIATION 7.77 | 29.0 kg/cm2 STANDARD_DEVIATION 7.81 |
| Region of Enrollment ARG | 108 participants | 108 participants | 216 participants |
| Region of Enrollment AUS | 18 participants | 16 participants | 34 participants |
| Region of Enrollment BGR | 35 participants | 32 participants | 67 participants |
| Region of Enrollment BRA | 73 participants | 77 participants | 150 participants |
| Region of Enrollment CAN | 240 participants | 236 participants | 476 participants |
| Region of Enrollment CHL | 25 participants | 25 participants | 50 participants |
| Region of Enrollment CHN | 154 participants | 160 participants | 314 participants |
| Region of Enrollment COL | 15 participants | 15 participants | 30 participants |
| Region of Enrollment DEU | 3 participants | 3 participants | 6 participants |
| Region of Enrollment FRA | 51 participants | 47 participants | 98 participants |
| Region of Enrollment GRC | 24 participants | 24 participants | 48 participants |
| Region of Enrollment IND | 499 participants | 502 participants | 1001 participants |
| Region of Enrollment ISR | 38 participants | 40 participants | 78 participants |
| Region of Enrollment ITA | 36 participants | 36 participants | 72 participants |
| Region of Enrollment KOR | 74 participants | 74 participants | 148 participants |
| Region of Enrollment LTU | 48 participants | 49 participants | 97 participants |
| Region of Enrollment MEX | 108 participants | 111 participants | 219 participants |
| Region of Enrollment MYS | 38 participants | 37 participants | 75 participants |
| Region of Enrollment NLD | 71 participants | 70 participants | 141 participants |
| Region of Enrollment NOR | 27 participants | 29 participants | 56 participants |
| Region of Enrollment NZL | 7 participants | 7 participants | 14 participants |
| Region of Enrollment POL | 134 participants | 133 participants | 267 participants |
| Region of Enrollment ROU | 24 participants | 28 participants | 52 participants |
| Region of Enrollment RUS | 148 participants | 147 participants | 295 participants |
| Region of Enrollment SGP | 27 participants | 26 participants | 53 participants |
| Region of Enrollment SWE | 2 participants | 3 participants | 5 participants |
| Region of Enrollment THA | 23 participants | 23 participants | 46 participants |
| Region of Enrollment TWN | 38 participants | 39 participants | 77 participants |
| Region of Enrollment UKR | 97 participants | 92 participants | 189 participants |
| Region of Enrollment USA | 1379 participants | 1388 participants | 2767 participants |
| Sex: Female, Male Female | 1197 Participants | 1247 Participants | 2444 Participants |
| Sex: Female, Male Male | 2367 Participants | 2330 Participants | 4697 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 366 / 3,498 | 364 / 3,509 |
| serious Total, serious adverse events | 5 / 3,498 | 2 / 3,509 |
Outcome results
Primary
Composite of Rehospitalization Due to Heart Failure and All-Cause Mortality
Time frame: Randomization to Day 30
Population: The modified intent-to-treat (MITT) population consisted of all randomized patients who received any amount of study medication and was the primary analysis population for all efficacy endpoints. 141 and 164 patients in the nesiritide and placebo groups, respectively, were not MITT population eligible or didn't have outcome measure of interest.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nesiritide | Composite of Rehospitalization Due to Heart Failure and All-Cause Mortality | 321 Participants |
| Placebo | Composite of Rehospitalization Due to Heart Failure and All-Cause Mortality | 345 Participants |
p-value: 0.31395% CI: [-2.1, 0.7]Cochran-Mantel-Haenszel
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.)
Time frame: 24 hours after study drug initiation
Population: The modified intent-to-treat (MITT) population consisted of all randomized patients who received any amount of study medication and was the primary analysis population for all efficacy endpoints. 193 and 179 patients in the nesiritide and placebo groups, respectively, were not MITT population eligible or didn't have outcome measure of interest.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nesiritide | Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug | Minimally Better | 716 Participants |
| Nesiritide | Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug | Minimally Worse | 27 Participants |
| Nesiritide | Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug | Moderately Better | 1274 Participants |
| Nesiritide | Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug | Moderately Worse | 7 Participants |
| Nesiritide | Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug | No Change | 291 Participants |
| Nesiritide | Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug | Markedly Worse | 31 Participants |
| Nesiritide | Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug | Markedly Better | 1025 Participants |
| Placebo | Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug | Markedly Worse | 25 Participants |
| Placebo | Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug | Markedly Better | 935 Participants |
| Placebo | Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug | Moderately Better | 1313 Participants |
| Placebo | Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug | Minimally Better | 751 Participants |
| Placebo | Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug | No Change | 323 Participants |
| Placebo | Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug | Minimally Worse | 36 Participants |
| Placebo | Dyspnea Self-Assessment at 24 Hours After Initiation of Study Drug | Moderately Worse | 15 Participants |
p-value: 0.007Van Elteren test
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.)
Time frame: 6 hours after initiation of study drug
Population: The modified intent-to-treat (MITT) population consisted of all randomized patients who received any amount of study medication and was the primary analysis population for all efficacy endpoints. 148 and 133 patients in the nesiritide and placebo groups, respectively, were not MITT population eligible or didn't have outcome measure of interest.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nesiritide | Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug | Minimally Better | 1119 Participants |
| Nesiritide | Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug | Minimally Worse | 39 Participants |
| Nesiritide | Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug | Moderately Better | 1007 Participants |
| Nesiritide | Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug | Moderately Worse | 12 Participants |
| Nesiritide | Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug | No Change | 692 Participants |
| Nesiritide | Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug | Markedly Worse | 34 Participants |
| Nesiritide | Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug | Markedly Better | 513 Participants |
| Placebo | Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug | Markedly Worse | 20 Participants |
| Placebo | Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug | Markedly Better | 460 Participants |
| Placebo | Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug | Moderately Better | 989 Participants |
| Placebo | Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug | Minimally Better | 1174 Participants |
| Placebo | Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug | No Change | 748 Participants |
| Placebo | Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug | Minimally Worse | 40 Participants |
| Placebo | Dyspnea Self-Assessment at 6 Hours After Initiation of Study Drug | Moderately Worse | 13 Participants |
p-value: 0.03Van Elteren test
Secondary
Composite of Cardiovascular Rehospitalization and Cardiovascular Mortality
Time frame: Randomization to Day 30
Population: The modified intent-to-treat (MITT) population consisted of all randomized patients who received any amount of study medication and was the primary analysis population for all efficacy endpoints. 141 and 162 patients in the nesiritide and placebo groups, respectively, were not MITT population eligible or didn't have outcome measure of interest.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nesiritide | Composite of Cardiovascular Rehospitalization and Cardiovascular Mortality | 372 Participants |
| Placebo | Composite of Cardiovascular Rehospitalization and Cardiovascular Mortality | 402 Participants |
p-value: 0.23895% CI: [-2.4, 0.6]Cochran-Mantel-Haenszel
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.
Time frame: Randomization to hospital discharge (up to Day 30)
Population: The modified intent-to-treat (MITT) population consisted of all randomized patients who received any amount of study medication and was the primary analysis population for all efficacy endpoints. 105 and 115 patients in the nesiritide and placebo groups, respectively, were not MITT population eligible or didn't have outcome measure of interest.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nesiritide | Composite of Persistent or Worsening Heart Failure and All-Cause Mortality | 147 Participants |
| Placebo | Composite of Persistent or Worsening Heart Failure and All-Cause Mortality | 165 Participants |
p-value: 0.29595% CI: [-1.5, 0.5]Cochran-Mantel-Haenszel
Secondary
Number of Days Alive and Outside the Hospital
Time frame: Randomization to Day 30
Population: The modified intent-to-treat (MITT) population consisted of all randomized patients who received any amount of study medication and was the primary analysis population for all efficacy endpoints. 182 and 188 patients in the nesiritide and placebo groups, respectively, were not MITT population eligible or didn't have outcome measure of interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nesiritide | Number of Days Alive and Outside the Hospital | 20.9 Days | Standard Deviation 6.88 |
| Placebo | Number of Days Alive and Outside the Hospital | 20.7 Days | Standard Deviation 7.05 |
p-value: 0.16ANOVA
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.)
Time frame: 24 hours after study drug initiation
Population: The modified intent-to-treat (MITT) population consisted of all randomized patients who received any amount of study medication and was the primary analysis population for all efficacy endpoints. 200 and 194 patients in the nesiritide and placebo groups, respectively, were not MITT population eligible or didn't have outcome measure of interest.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nesiritide | Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug | Minimally Better | 761 Participants |
| Nesiritide | Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug | Minimally Worse | 31 Participants |
| Nesiritide | Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug | Moderately Better | 1297 Participants |
| Nesiritide | Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug | Moderately Worse | 16 Participants |
| Nesiritide | Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug | No Change | 310 Participants |
| Nesiritide | Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug | Markedly Worse | 36 Participants |
| Nesiritide | Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug | Markedly Better | 913 Participants |
| Placebo | Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug | Markedly Worse | 26 Participants |
| Placebo | Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug | Markedly Better | 843 Participants |
| Placebo | Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug | Moderately Better | 1311 Participants |
| Placebo | Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug | Minimally Better | 798 Participants |
| Placebo | Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug | No Change | 331 Participants |
| Placebo | Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug | Minimally Worse | 52 Participants |
| Placebo | Overall Well-Being Self-Assessment at 24 Hours After Initiation of Study Drug | Moderately Worse | 22 Participants |
p-value: 0.018Van Elteren test
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.)
Time frame: 6 hours after study drug initiation
Population: The modified intent-to-treat (MITT) population consisted of all randomized patients who received any amount of study medication and was the primary analysis population for all efficacy endpoints. 158 and 147 patients in the nesiritide and placebo groups, respectively, were not MITT population eligible or didn't have outcome measure of interest.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nesiritide | Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug | Minimally Better | 1154 Participants |
| Nesiritide | Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug | Minimally Worse | 42 Participants |
| Nesiritide | Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug | Moderately Better | 962 Participants |
| Nesiritide | Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug | Moderately Worse | 17 Participants |
| Nesiritide | Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug | No Change | 751 Participants |
| Nesiritide | Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug | Markedly Worse | 31 Participants |
| Nesiritide | Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug | Markedly Better | 449 Participants |
| Placebo | Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug | Markedly Worse | 16 Participants |
| Placebo | Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug | Markedly Better | 418 Participants |
| Placebo | Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug | Moderately Better | 965 Participants |
| Placebo | Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug | Minimally Better | 1186 Participants |
| Placebo | Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug | No Change | 785 Participants |
| Placebo | Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug | Minimally Worse | 49 Participants |
| Placebo | Overall Well-Being Self-Assessment at 6 Hours After Initiation of Study Drug | Moderately Worse | 11 Participants |
p-value: 0.318Van Elteren test
Other Pre-specified
All-Cause Mortality Through Day 180
All deaths were adjudicated by an independent Clinical Events Committee.
Time frame: Randomization to Day 180
Population: The safety population consisted of all randomized patients who received any amount of study medication. For all safety analyses, patients were analyzed according to the treatment actually received. 66 and 68 patients in the nesiritide and placebo groups, respectively, were not included in the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nesiritide | All-Cause Mortality Through Day 180 | 429 Participants |
| Placebo | All-Cause Mortality Through Day 180 | 447 Participants |
Other Pre-specified
All-Cause Mortality Through Day 30
All deaths were adjudicated by an independent Clinical Events Committee.
Time frame: Randomization to Day 30
Population: The safety population consisted of all randomized patients who received any amount of study medication. For all safety analyses, patients were analyzed according to the treatment actually received. 66 and 68 patients in the nesiritide and placebo groups, respectively, were not included in the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nesiritide | All-Cause Mortality Through Day 30 | 126 Participants |
| Placebo | All-Cause Mortality Through Day 30 | 141 Participants |
Other Pre-specified
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.
Time frame: Randomization to Day 30
Population: The safety population consisted of all randomized patients who received any amount of study medication. For all safety analyses, patients were analyzed according to the treatment actually received. 66 and 68 patients in the nesiritide and placebo groups, respectively, were not included in the safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nesiritide | Cardiovascular Mortality Through Day 30 | Worsening Heart Failure | 68 Participants |
| Nesiritide | Cardiovascular Mortality Through Day 30 | Sudden Cardiac Death | 20 Participants |
| Nesiritide | Cardiovascular Mortality Through Day 30 | Total Cardiovascular Deaths | 112 Participants |
| Nesiritide | Cardiovascular Mortality Through Day 30 | Myocardial Infarction | 4 Participants |
| Nesiritide | Cardiovascular Mortality Through Day 30 | Presumed Cardiovascular Cause | 9 Participants |
| Nesiritide | Cardiovascular Mortality Through Day 30 | Other Cardiovascular Cause | 11 Participants |
| Placebo | Cardiovascular Mortality Through Day 30 | Presumed Cardiovascular Cause | 11 Participants |
| Placebo | Cardiovascular Mortality Through Day 30 | Total Cardiovascular Deaths | 124 Participants |
| Placebo | Cardiovascular Mortality Through Day 30 | Worsening Heart Failure | 80 Participants |
| Placebo | Cardiovascular Mortality Through Day 30 | Myocardial Infarction | 0 Participants |
| Placebo | Cardiovascular Mortality Through Day 30 | Sudden Cardiac Death | 23 Participants |
| Placebo | Cardiovascular Mortality Through Day 30 | Other Cardiovascular Cause | 10 Participants |
Other Pre-specified
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.
Time frame: Study drug initiation to Day 30
Population: The safety population consisted of all randomized patients who received any amount of study medication. For all safety analyses, patients were analyzed according to the treatment actually received. 66 and 68 patients in the nesiritide and placebo groups, respectively, were not included in the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nesiritide | Number of Patients With Renal Impairment | 1032 Participants |
| Placebo | Number of Patients With Renal Impairment | 968 Participants |
p-value: 0.10995% CI: [0.98, 1.21]Cochran-Mantel-Haenszel