Double-Blind, Placebo-Controlled, Multicenter Acute Study of Clinical Effectiveness of Nesiritide in Subjects with Decompensated Heart Failure
- Conditions
- Heartfailureweakness of the heart10019280
- Registration Number
- NL-OMON31659
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 75
- Men or women 18 years of age or older
- Hospitalized for the management of ADHF or diagnosed with ADHF within 48 hours after being hospitalized for another reason
- Diagnosis of ADHF must meet the following definition:
- Dyspnea at rest or dyspnea with minimal activity
AND at least 1 of the following signs:
- Tachypnea with respiratory rate >20 breaths per minute, OR
- Pulmonary congestion/edema with rales or crackles/crepitations at least one-third above lung base
AND at least 1 of the following objective measures:
- Chest x-ray with pulmonary congestion/edema, OR
- B-type natriuretic peptide ³400 pg/mL or NT-proBNP ³1,000 pg/mL at presentation, OR
- Pulmonary capillary wedge pressure >20 mmHg, OR
- Ejection fraction <40% measured by any modality (echocardiography, nuclear testing, cardiac MRI, ventricular angiography) within 12 months before randomization without intervening revascularization or cardiac surgery
- Hospitalized for more than 48 hours before randomization
- Likely to be discharged from the hospital in 24 hours or less
- At high risk for hypotension:
- Baseline SBP <100 mmHg or
- Systolic blood pressure <110 mmHg with i.v. nitroglycerin or another i.v. vasodilator used at baseline
- Persistent, uncontrolled hypertension (SBP >180 mmHg)
- Have any of the following cardiovascular disease parameters:
- Echocardiogram (ECG) with new ST elevation >1 mm in 2 consecutive leads
- Acute coronary syndrome as primary diagnosis
- A coronary catheterization or other coronary intervention is planned within 48 hours
- History of cardiac valvular stenosis, restrictive cardiomyopathy, hypertrophic obstructive cardiomyopathy, or pericardial tamponade
- PCWP =<20 mmHg within 6 hours before randomization (only if measured)
- Have a left ventricular assist device
- Medication History:
- Received first i.v. treatment of diuretics, vasodilators or inotropes for HF more than 24 hours before randomization
- Treated with levosimendan or milrinone within 30 days before randomization or anticipated need for one of these medications during the current hospitalization
- Treated with i.v. nitroglycerin, i.v. dobutamine <5 mg/kg/min or another i.v. vasoactive medication, the dosage of which is not stable for 3 hours before randomization
- Treated with dobutamine >= 5 mg/kg/min. at the time of randomization
- Had prior therapy with nesiritide in the past 30 days, or anticipate the need for open-label nesiritide during the current hospitalization
- Known allergic reaction or hypersensitivity to nesiritide
- Laboratory abnormalities (when laboratory values are available)
- Troponin level >5 times the upper limit of normal (ULN)
- Creatine kinase - MB (CK-MB) levels >3 times ULN
- BNP or NT-proBNP is within normal limits (i.e., BNP <100 pg/mL or NT-proBNP <125 pg/mL for subjects <75 years old; NT proBNP <425 pg/mL for subjects >=75 years old)
Comorbid Diseases
- Chronic or intermittent renal support therapy (hemodialysis, ultrafiltration, or peritoneal dialysis)
- Significant chronic or acute lung disease that might interfere with the ability to interpret the dyspnea assessments
- Serious comorbid disease in which the life expectancy of the subject is less than 6 months
- Anemia
- Active gastrointestinal bleeding
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The study has two co-primary hypotheses:<br /><br>· Nesiritide administered in addition to standard care is superior to placebo<br /><br>administered in addition to standard care in the reduction of the composite<br /><br>endpoint of HF rehospitalization and all-cause mortality from randomization<br /><br>through Day 30 in subjects with ADHF, and<br /><br>· Nesiritide administered in addition to standard care is superior to placebo<br /><br>administered in addition to standard care in relieving dyspnea symptoms, as<br /><br>measured by self-assessed Likert scale at 6 or 24 hours after study drug<br /><br>initiation, in subjects with ADHF</p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary objectives of this study are to evaluate the effect of treatment<br /><br>with nesiritide, compared with placebo, when each is administered in addition<br /><br>to standard care in ADHF, in:<br /><br>· Improving subject self-assessed overall well-being at 6 or 24 hours after<br /><br>study drug initiation<br /><br>· Increasing the number of days alive and outside of the hospital from<br /><br>randomization through Day 30<br /><br>· Reducing the composite of cardiovascular rehospitalization and cardiovascular<br /><br>mortality from randomization through Day 30<br /><br>- the effect on persistent or worsening of heart failure from randomization<br /><br>through index hospitalization (amendment INT-1).</p><br>