The Clinical Study of the Safety and Efficacy of Istaroxime in Treatment of Acute Decompensated Heart Failure

Inclusion Criteria: Patients who fulfill the following inclusion criteria at screening will be considered forthe study:

1. Signed informed consent;
2. Male or female patients 18-85 years (inclusive);
3. Admission for a recurrent acute decompensated heart failure (ADHF) episode withdyspnea at rest or minimal exertion and need of intravenous diuretic therapy (≥40 mgiv. furosemide);
4. Systolic blood pressure between 90 and 125 mmHg (limits included) without signs orsymptoms of hypoperfusion including cardiogenic shock, cold extremities and peripheralvasoconstriction, oliguria/anuria, signs of cerebral hypo perfusion such as confusion;
5. Left ventricular (LV) Ejection fraction (EF) ≤ 40 % measured by 2D-Echocardiography
6. E/Ea ratio >10
7. BNP ≥ 350pg/mL or NT-pro-BNP ≥1400 pg/mL
8. Adequate echocardiography window (defined as visualization of at least 13/16 segmentof the left ventricle);

Exclusion Criteria: Any of the following criteria established at screening would render a patient ineligiblefor the study:

1. Pregnant or breast-feeding women (women of child bearing potential must have theresults of a negative pregnancy test recorded prior to study drug administration)
2. Current (within 12 hours prior to screening) or planned (through the completion ofstudy drug infusion) treatment with any iv. therapies, including vasodilators (including nitrates or nesiritide), positive inotropic agents and vasopressors
3. Current or need of mechanical support (intra-aortic balloon pump, endotrachealintubation, mechanical ventilation, or any ventricular assist device),
4. Ongoing treatment with oral digoxin. Patient treated with digoxin within the lastweek, can be randomised if the plasma concentration of digoxin is tested beforerandomization and its value will be less than 0.5 ng/ml.
5. History of hypersensitivity to the study medication or any related medication
6. Diagnosis of cardiogenic shock within the past month;
7. Acute coronary syndrome or stroke within the past 3 months;
8. Coronary artery bypass graft or percutaneous coronary intervention within the pastmonth or planned in the next month;
9. Primary hypertrophic or restrictive cardiomyopathy or systemic illness known to beassociated with infiltrative heart disease;
10. Cor pulmonale or other causes of right-sided heart failure (HF) not related to leftventricular dysfunction;
11. Pericardial constriction or active pericarditis;
12. Atrial fibrillation with marked irregularities of heart rhythm;
13. Life threatening ventricular arrhythmia or implantable cardioverter-defibrillator (ICD) shock within the past month;
14. Cardiac resynchronization therapy (CRT), ICD, or pacemaker implantation within thepast month;
15. Valvular disease as primary cause of HF;
16. Heart rate >120 bpm or < 50 bpm
17. Acute respiratory distress syndrome or ongoing sepsis;
18. Fever >38°
19. History of bronchial asthma or porphyria;
20. Donation or loss of blood equal to or exceeding 500 mL, during the 8 weeks beforeadministration of study medication;
21. Positive testing for HIV, Hepatitis B and/or Hepatitis C;
22. Participation in another interventional study within the past 30 days;
23. The following laboratory exclusion criteria, verified based on results obtained withinthe last 24 hours of hospitalization:
24. Serum creatinine > 3.0 mg/dl (> 265 µmol/L);
25. Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) > 3 x upperlimit of normal,
26. Hemoglobin (Hb) < 10 g/dL,
27. Platelet count < 100,000/µL,
28. Serum potassium > 5.3 mmol/L or < 3.8 mmol/L,