Acute heart failure decompensated MedDRA version: 14.1 Level: LLT Classification code 10066332 Term: Acute cardiac insufficiency System Organ Class: 100000004849
Conditions
Interventions
Product Name: Istaroxime
Product Code: PST2744
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: Istaroxime
CAS Number: 374559-48-5
Current Sponsor code: PST 2744
Sponsors
CVie Therapeutics Company Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent; 2. Male or female patients = 18 years; 3. Admission for a recurrent ADHF episode with dyspnea at rest or minimal exertion and need of intravenous diuretic therapy (>40 mg iv. furosemide); 4. Systolic blood pressure between 90 and 125 mmHg (limits included) without signs or symptoms of hypoperfusion including cardiogenic shock, cold extremities and peripheral vasoconstriction, 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 segment of the left ventricle); 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 18 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. Pregnant or breast-feeding women (women of child bearing potential must have the results of a negative pregnancy test recorded prior to study drug administration); 2. Current (within 12 hours prior to screening) or planned (through the completion of study 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, endotracheal intubation, mechanical ventilation, or any ventricular assist device); 4. Ongoing treatment with oral digoxin. Patient treated with digoxin within the last week, can be randomised if the plasma concentration of digoxin are tested before randomization and its value will be less than 0.5 ng/ml; 5. History of hypersensitivity to the study 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 past month or planned in the next month; 9. Primary hypertrophic or restrictive cardiomyopathy or systemic illness known to be associated with infiltrative heart disease; 10. Cor pulmonale or other causes of right-sided HF not related to left ventricular dysfunction; 11. Pericardial constriction or active pericarditis; 12. Atrial fibrillation with market irregularities of heart rhythm; 13. Life threatening ventricular arrhythmia or ICD (implantable cardioverter defibrillator) shock within the past month; 14. CRT (cardiac resynchronization therapy), ICD or pacemaker implantation within the past month; 15. Valvular disease as primary cause of HF; 16. Heart rate >120 bpm or 38°; 19. History of bronchial asthma or porphyria; 20. Donation or loss of blood equal to or exceeding 500 mL, during the 8 weeks before administration 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 within the last 24 hours of hospitalization: a. Serum creatinine > 3.0 mg/dl (> 265 µmol/L); b. Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) > 3 x upper limit of normal, c. Hemoglobin (Hb) 5.3 mmol/L or < 3.8 mmol/L.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To Assess the safety, tolerability and efficacy of two different doses of istaroxime (0.5 and 1.0 µg/kg/min), a new agent with lusitropic and inotropic activities that improves the cardiac contraction-relaxation cycle. The 2 doses of istaroxime (0.5 and 1.0 µg/kg/min) will be infused i. v. for 24 hours in comparison with placebo, in treatment of Chinese and Italian patients with Acute Decompensated Heart Failure.;Secondary Objective: In all Italian patients and in a subset of Chinese patients pharmacokinetics and metabolism of istaroxime shall also be studied;Primary end point(s): Change from baseline to 24 hours after infusion start (treatment period Day 1) in the E/Ea ratio assessed by tissue Doppler.;Timepoint(s) of evaluation of this end point: 1 day (24 hours) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: • Change from baseline to 24 hours in the treatment period Day1 (addressing the differences between the changes at 6 and 24 hours from baseline) of the following Echo-Doppler parameters: - LV Ejection fraction (EF) - LV end systolic and end diastolic volumes - Stroke volume index (SVI) - E, A and E/A ratio • Difference between the changes at 6 and 24 hours from baseline of the Tissue Doppler parameter E/Ea • Others Tissue Doppler parameters such as Sa, Da and Aa • Changes in dyspnoea assessed at 3, 6, 12, 24, 48 hours after infusion start by Visual Analog Scale (VAS) (including only patients presenting dyspnoea at baseline); • Area under the curve (AUC) on changes in dyspnoea assessed at 3, 6, 12, 24, 48 hours after infusion start by VAS (including only patients presenting dyspnea at baseline); • Changes in BNP from baseline at 24 hours; • Proportion of patients with hospital readmissions or emergency visits for cardiovascular reasons by Day 30; • Proportion of patients with episodes of worsening HF defined by the need to increase the dose or reinitiate i.v. therapy with diuretics and/ or other inotropic agents during the hospitalization; • Length of the hospitalization. Safety: • Incidence of adverse events; • Change in vital signs (including body temperature and dyspnoea); • Change in 12-lead ECG parameters; • Incidence of clinically or hemodynamically significant episodes of supraventricular or ventricular arrhythmias detected by continuous ECG dynamic monitoring; • Change in laboratory parameters (hematology, blood chemistry and urinalysis); • Change in renal function; • Change in in cTnT; • Incidence of cTnT elevation (>50% or > 20% relative increase over the basal cTnT levels at baseline, for patients with cTnT levels at baseline < or = of the 99% URL (upper reference levels, as defined for the Roche hs test), respectively); • Mortality at Day 30. PK: The following PK metrics will be computed for E | — |
Countries
China, Italy
Contacts
Public ContactPaola Minguzzi
Cronos Ricerche Cliniche srl
Outcome results
None listed