acute decompensated heart failure MedDRA version: 9.1 Level: LLT Classification code 10064653 Term: Acute decompensated heart failure
Conditions
Interventions
Product Name: istaroxime
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Digoxin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pha
Sponsors
DEBIOPHARM S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Screening Inclusion Criteria 1. Male or female patients ≥18 years; 2. Enrolled into the study during the first 48 hours of hospitalization; 3. Admission for ADHF defined as dyspnea at rest or orthopnea, with or without chest x-ray findings of pulmonary congestion; 4. Systolic blood pressure ≤ 120 mmHg; 5. Ejection fraction (EF) ≤ 35 % by any method (to be performed if not measured within the last 12 months); 6. Signed informed consent. Randomization Inclusion Criteria 1. Persistence of ADHF signs (JVD, pulmonary rales, peripheral edema) despite initial treatment with i.v. diuretics and/or vasodilators; 2. Cardiac index ≤ 2.5 L/min/m²; 3. Pulmonary capillary wedge pressure  20 mmHg: 2 consecutive determinations at 30 minute intervals should not exceed a maximum of 10% variability; if the first 2 consecutive determinations fail to show the required stability, further determinations are allowed at the same interval within a maximum of 2 hours of evaluation. If stability is not demonstrated by 2 consecutive determinations within the 2-hour period, the patient will be excluded from the study. 4. Systolic BP comprised between 85 and 120 mmHg (limits included) without signs or symptoms of hypoperfusion including cardiogenic shock, cold extremities and peripheral vasoconstriction, oliguria/anuria, signs of cerebral hypoperfusion such as confusion. 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
Exclusion criteria: Screening Exclusion Criteria 1. Positive pregnancy test in females of childbearing potential; 2. Systolic blood pressure 120 mmHg; 3. Oral treatment with digoxin within one week before current hospitalization; 4. Any inotrope administered during the current hospitalization (e.g. dobutamine, dopamine, milrinone, levosimendan, digoxin, enoximone); 5. Presence of cardiogenic shock or its occurrence within the past month; 6. Acute coronary syndrome within the past 3 months; 7. Coronary artery bypass graft or percutaneous coronary intervention within the past month; 8. Stroke within the past 6 months; 9. Primary hypertrophic or restrictive cardiomyopathy or systemic illness known to be associated with infiltrative heart disease; 10. Presence of signs or symptoms of uncontrolled hyperthyroidism or hypothyroidism; 11. Cor pulmonale or other causes of right-sided HF not related to left ventricular dysfunction; 12. Pericardial constriction or active pericarditis; 13. Atrial fibrillation with uncontrolled HR (HR > 100 beats per minute bpm); 14. Life threatening ventricular arrhythmia or ICD (implantable cardioverter defibrillator) shock within the past month; 15. Presence of a CRT (cardiac resynchronization therapy), ICD or pacemaker devices implanted within the past month; 16. Second or third degree atrio-ventricular block without pacemaker; 17. Valvular disease as the primary cause of HF; 18. Hemodynamic support devices; 19. Need for mechanical ventilation; 20. Acute respiratory distress syndrome or ongoing sepsis; 21. Terminal illness other than HF with expected survival less than 1 year; 22. Participation in another interventional study within the past 30 days; 23. The following laboratory exclusion criteria must be verified based on results obtained within the last 24 hours of the screening period prior to pulmonary arterial catheter (PAC) insertion: a. Serum creatinine > 2.5 mg/dL (> 221 µmol/L), b. Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) > 3 x upper limit of normal, c. Hemoglobin (Hb) 1.4 in patients not receiving anticoagulant therapy, e. Platelet count 120 bpm or < 50 bpm.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to assess the hemodynamic effects of istaroxime in patients with ADHF not requiring inotropic therapy at admission and receiving one of 3 doses (0.5, 1.0, and 1.5 µg/kg/min) of istaroxime i.v. infusion for 24 hours.;Secondary Objective: To assess clinical efficacy and safety including cardiovascular and renal tolerability as well as changes in biological markers such as brain natriuretic peptide (BNP) and troponin I (TNI), and the neurohormones renin and aldosterone; To assess the PK of istaroxime and its metabolites (plasma concentration at infusion end in all patients and full PK profile in a subset of about 56 patients).;Primary end point(s): Efficacy endpoints Primary hemodynamic endpoint PCWP change from baseline at 6 hours after infusion start. Secondary hemodynamic endpoints - PCWP change from baseline at 1, 3, 12, and 24 hours after infusion start, and at 1 and 3 hours after infusion end; - MRAP and systolic, diastolic and mean PAP change from baseline at 1, 3, 6, 12, and 24 hours after infusion start, and at 1 and 3 hours after infusion end; - SVR and PVR change from baseline at 6 and 24 hours after infusion start, and at 1 and 3 hours after infusion end (values will be calculated on the basis of vital sign recordings); - Cardiac output and its indexed value (cardiac index) change from baseline at 1, 3, 6, 12, and 24 hours after infusion start, and at 1 and 3 hours after infusion end; - SBP change from baseline at 1, 3, 6, 12 and 24 hours after infusion start, and at 1 and 3 hours after infusion end. Safety endpoints The following safety endpoints will be assessed during treatment and the post-treatment/follow-up periods: - Incidence of AEs; - Vital signs (HR, systolic, diastolic and mean BP, respiratory rate) change from baseline at 1, 3, 6, 12, and 24 hours after infusion start, and 1 and 3 hours after infusion end, and then in the morning on study Day 3 and Day 5 or at discharge(a), and on study Day 30 during the follow up visit; - ECG ( | — |
Countries
France, Italy, Lithuania
Outcome results
None listed