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

• Register: EUCTR
• Last refreshed on: 3 September 2012
• Main ID: EUCTR2007-001670-84-SE
• Date of registration: 21/08/2007
• Prospective Registration: Yes
• Primary sponsor: Jassen-Cilag International NV,Turnhoutseweg 30, 2340 Beerse, Belgium
• Public title: Double-Blind, Placebo-Controlled, Multicenter Acute Study of Clinical Effectiveness of Nesiritide in Subjects with Decompensated Heart Failure - ASCEND-HF
• Scientific title: Double-Blind, Placebo-Controlled, Multicenter Acute Study of Clinical Effectiveness of Nesiritide in Subjects with Decompensated Heart Failure - ASCEND-HF
• Date of first enrolment: 04/10/2007
• Target sample size: 7000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-001670-84
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Bulgaria, France, Germany, Greece, Hungary, Italy, Lithuania, Netherlands, Sweden

Key inclusion & exclusion 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 <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)



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Acute Decompensated Heart Failure
MedDRA version: 9.1 Level: LLT Classification code 10064653 Term: Acute decompensated heart failure

Intervention(s)

Trade Name: Natrecor
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 milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.3-
Pharmaceutical form of the placebo: Powder and solvent for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

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

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 ID(s)

2007-001670-84-HU

A 093