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

• Conditions: Acute Decompensated Heart Failure; MedDRA version: 9.1Level: LLTClassification code 10064653Term: Acute decompensated heart failure

• Registration Number: EUCTR2007-001670-84-SE
• Lead Sponsor: Jassen-Cilag International NV,Turnhoutseweg 30, 2340 Beerse, Belgium

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-08-21
• Last Update Posted: 3 September 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 7000

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 <40% measured by any modality (echocardiography, nuclear testing, cardiac MRI, ventricular angiography) within 12 months before randomization without intervening revascularization or cardiac surgery

-Signed (by the subjects or their legally acceptable representatives) informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

-Signed (by the subjects or their legally acceptable representatives) informed consent form for pharmacogenomic research indicating consent or refusal to participate in the pharmacogenomic component of the study (where local regulations permit). Participation in this component is not required for participation in the clinical study

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 <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:
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 mg/kg/min or another i.v. vasoactive medication, the dosage of which is not stable for 3 hours before randomization
Treated with dobutamine greater than or equal to 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 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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified