Acute Decompensated Heart Failure MedDRA version: 9.1 Level: LLT Classification code 10064653 Term: Acute decompensated heart failure
Conditions
Interventions
Product Name: nesiritide
Product Code: JNJ-27410084
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Nesiritide
Current Sponsor code: JNJ-27410084
Concentration unit: mg/ml m
Sponsors
Jassen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -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 The diagnosis of ADHF must meet the following definition: –Dyspnea at rest or dyspnea with minimal activity (i.e., difficulty breathing at rest while sitting, or difficulty breathing while lying flat or with 1 pillow, or difficulty breathing with minimal activity such as talking, eating), 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 =400 pg/mL or NT-proBNP =1,000 pg/mL at presentation, OR – Pulmonary capillary wedge pressure >20 mmHg, OR – Ejection fraction =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Hospitalized for =48 hours before randomization - Likely to be discharged from the hospital in 24 hours or less At high risk for hypotension: -Baseline SBP 180 mmHg) Have any of the following cardiovascular disease parameters: Electrocardiogram (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 Cardiac index >2.5 l/min/m2 or PCWP =20 mmHg, or both, 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 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 greater than or equal to 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 (e.g., severe chronic obstructive pulmonary disease, active asthma or acute pneumonia) Serious comorbid disease in which the life expectancy of the subject is less than 6 months – e.g., acute systemic infection – sepsis, metastatic cancer or other serious illnesses Anemia, defined as hemoglobin <9 g/dL (<5.6 mmol/L) or hematocrit <27% Active gastrointestinal bleeding - Received an experimental drug or used an experimental medical device within 30 days before randomization - Previous enrollment in a nesiritide study - Pregnant, suspected to be pregnant, or breast-feeding - Unwillingness or inability to comply with study requirements (including subjects whose cooperation is doubtful due to drug abuse or alcohol dependency)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Primary Hypotheses: The study has two co-primary hypotheses: · Nesiritide administered in addition to standard care is superior to placebo administered in addition to standard care in the reduction of the composite endpoint of HF rehospitalization and all-cause mortality from randomization through Day 30 in subjects with ADHF, and · Nesiritide administered in addition to standard care is superior to placebo administered in addition to standard care in relieving dyspnea symptoms, as measured by self-assessed Likert scale at 6 or 24 hours after study drug initiation, in subjects with ADHF. ;Main Objective: The primary objective of this study is to evaluate whether treatment with nesiritide improves patient outcomes (as measured by reduction in the composite of HF rehospitalization and all-cause mortality through 30 days after randomization [Day 30]) or HF symptoms (as measured by subject self assessed Likert dyspnea scale at 6 hours and 24 hours after study drug initiation) compared with placebo when each is administered in addition to other standard therapies in patients with ADHF.;Secondary Objective: The secondary objectives of this study are to evaluate the effect of treatment with nesiritide, compared with placebo, when each is administered in addition to standard care in ADHF, in: (1) Improving subject self-assessed overall well-being as measured by self assessed Likert scale at 6 or 24 hours after study drug initiation (2) Increasing the number of days alive and outside the hospital from randomization through Day 30· (3) Reducing the composite of cardiovascular rehospitalization and cardiovascular mortality from randomization through Day 30 | — |
Countries
Belgium, Bulgaria, France, Germany, Greece, Hungary, Italy, Lithuania, Netherlands, Sweden
Outcome results
None listed