Acute Decompensated Heart Failure
Conditions
Keywords
safety, efficacy, istaroxime
Brief summary
To assess the safety, tolerability and efficacy of two different doses of istaroxime, 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 via i. v. for 24 hours in comparison with placebo, in treatment of Chinese and Italian patients with Acute Decompensated Heart Failure.
Detailed description
To assess the safety, tolerability and efficacy of two different doses of istaroxime (0.5 and 1.0 µg/kg/min) in comparison with placebo, including cardiovascular and renal tolerability, as well as changes in biological markers such as N-terminal prohormone brain natriuretic peptide (NT-proBNP) and troponin T (cTnT). The study will be conducted in 96 Chinese and Italian patients with Acute Decompensated Heart Failure. This is a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel group study. Patients were randomly assigned to one of two doses of istaroxime or placebo in a 2:1 ratio within two sequential cohorts of 60 patients each. This 31-day study includes a screening period (Days -1), a treatment period (Day 1), a post-treatment period (Days 2-4), and a follow-up period (which includes one patient visit on Day 30). In all the Italian patients and in a subset of Chinese patients pharmacokinetics and metabolism of istaroxime shall also be studied.
Interventions
DRUGPlacebo
IV of matching saline solution
DRUGIstaroxime
IV infusion of 0.5 µg/kg/min or 1.0 µg/kg/min istaroxime
Sponsors
Windtree Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
Cohort I: Participants enrolled in a 2:1 ratio to istaroxime 0.5 µg/kg/min or placebo. Cohort II: Participants enrolled in a 2:1 ratio to istaroxime 1.0 µg/kg/min or placebo. Cohort I was enrolled first, followed by Cohort II.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Patients who fulfill the following inclusion criteria at screening will be considered for the 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 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);
Exclusion criteria
Any of the following criteria established at screening would render a patient ineligible for the study: 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 is tested before randomization 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 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 heart failure (HF) not related to left ventricular 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 the past 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in E/Ea Ratio | 24 hours | Change from baseline at 24 hours in the unitless ratio of E (cm/sec) to Ea (or e') (cm/sec) as measured by echocardiogram. The endpoint is the Tissue Doppler echocardiography showing measurement of mitral E/Ea ratio for assessment of diastolic dysfunction. Initially mitral E wave is measured. After that, color Tissue Doppler (tissue velocity imaging or TVI) mode is switched on to assess tissue Doppler. The cursor is placed over the medial mitral annulus and tissue Doppler tracing obtained. This allows Ea velocity to be measured. Higher values are suggestive of a worse outcome; less than 8 is normal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in SVI | 24 hours | Change from baseline at 24 hours in stroke volume index (SVI) by tissue Doppler |
| Change in E/A Ratio | 24 hours | Change from baseline at 24 hours in E/A ratio by tissue Doppler |
| Change in LVEF | 24 hours | Change from baseline at 24 hours in LV ejection fraction (LVEF) by tissue Doppler |
| Change in LV End Diastolic Volume | 24 hours | Change from baseline in left ventricular end diastolic volume (LVEDV) by tissue Doppler |
| Change in Dyspnea | 24 hours | Measured using a visual analog scale (0 to 100). Higher scores indicate less dyspnea. |
| Change in LV End Systolic Volume | 24 hours | Change from baseline in left ventricular end systolic volume (LVESV) by tissue Doppler |
Other
| Measure | Time frame | Description |
|---|---|---|
| RBC - Shift | Day 3 | Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in red blood cells (RBC) |
| Hematocrit - Shift | Day 3 | Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in hematocrit |
| Hemoglobin - Shift | Day 3 | Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in hemoglobin |
| White Blood Cells (WBC) - Shift | Day 3 | Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in WBC |
| Platelets - Shift | Day 3 | Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in platelets |
| Potassium - Shift | Day 3 | Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in potassium |
| Change in cTnT | 24 hours | Safety endpoint: Changes in troponin (cTnT) |
| Calcium - Shift | Day 3 | Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in calcium |
| BUN - Shift | Day 3 | Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in blood urea nitrogen (BUN) |
| ALT - Shift | Day 3 | Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in alanine aminotransferase (ALT) |
| AST - Shift | Day 3 | Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in aspartate aminotransferase (AST) |
| Total Bilirubin - Shift | Day 3 | Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in total bilirubin |
| Sodium - Shift | Day 3 | Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in sodium |
| Change in eGFR | 24 Hours | Safety endpoint: Change from baseline in estimated glomerular filtration rate (eGFR) |
| Participants With Clinically or Hemodynamically Significant Episodes of Arrhythmias | 24 hours | Safety endpoint: Number of participants with incidence of clinically or hemodynamically significant episodes of supraventricular or ventricular arrhythmias detected by continuous ECG dynamic monitoring |
| PR Interval | 24 Hours | Safety Endpoint: The PR interval, measured in milliseconds, extends from the beginning of the P wave (the onset of atrial depolarization) until the beginning of the QRS complex (the onset of ventricular depolarization). |
| QRS Duration | 24 hours | Safety endpoint: The quasi-random signal (QRS) duration represents the time for ventricular depolarization, normally 0.06 to 0.10 seconds. |
| QTc Interval | 24 Hours | Safety Endpoint: The corrected QT interval (QTc) on an ECG represents the duration in milliseconds of the ventricular action potential, which physiologically correlates with the duration of the ventricular depolarization and repolarization. |
| All-Cause Mortality at Day 30 | 30 days | Safety endpoint: Mortality at Day 30 |
Countries
China, Italy
Participant flow
Pre-assignment details
Screening to assess whether the patient qualified for the study. 144 patients were screened, 22 were determined to be screen failures and additional 2 patients were excluded for not meeting inclusion/exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Placebo IV infusion for 24 hours
Placebo: IV of matching saline solution | 39 |
| Istaroxime 0.5 µg/kg/Min Istaroxime via IV infusion for 24 hours
Istaroxime: IV infusion of istaroxime 0.5 µg/kg/min | 41 |
| Istaroxime 1.0 µg/kg/Min Istaroxime via IV infusion for 24 hours
Istaroxime: IV infusion of istaroxime 1.0 µg/kg/min | 40 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 5 |
| Overall Study | Death | 0 | 0 | 2 |
| Overall Study | Lost to Follow-up | 3 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Istaroxime 0.5 µg/kg/Min | Total | Placebo | Istaroxime 1.0 µg/kg/Min |
|---|---|---|---|---|
| Age, Continuous | 59.73 years STANDARD_DEVIATION 15.53 | 56.24 years STANDARD_DEVIATION 14.98 | 56.67 years STANDARD_DEVIATION 16.21 | 52.23 years STANDARD_DEVIATION 13.02 |
| Dyspnea | 73.6 Scores on a scale STANDARD_DEVIATION 19.49 | 72.0 Scores on a scale STANDARD_DEVIATION 20.59 | 70.8 Scores on a scale STANDARD_DEVIATION 21.32 | 71.5 Scores on a scale STANDARD_DEVIATION 20.95 |
| E/Ea Ratio | 20.4 Unitless ratio STANDARD_DEVIATION 7.87 | 17.5 Unitless ratio STANDARD_DEVIATION 6.36 | 17.0 Unitless ratio STANDARD_DEVIATION 5.33 | 15.1 Unitless ratio STANDARD_DEVIATION 5.48 |
| eGFR | 72.3 ml/min/1.73·m² STANDARD_DEVIATION 30.93 | 77.2 ml/min/1.73·m² STANDARD_DEVIATION 32.36 | 78.1 ml/min/1.73·m² STANDARD_DEVIATION 38.33 | 81.3 ml/min/1.73·m² STANDARD_DEVIATION 27.01 |
| Left ventricular ejection fraction (LVEF) | 27.4 % of blood in heart pumped STANDARD_DEVIATION 6.7 | 27.4 % of blood in heart pumped STANDARD_DEVIATION 7.1 | 26.2 % of blood in heart pumped STANDARD_DEVIATION 7.4 | 28.7 % of blood in heart pumped STANDARD_DEVIATION 7.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 24 Participants | 96 Participants | 32 Participants | 40 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 24 Participants | 7 Participants | 0 Participants |
| Region of Enrollment China | 24 participants | 96 participants | 32 participants | 40 participants |
| Region of Enrollment Italy | 17 participants | 24 participants | 7 participants | 0 participants |
| Sex: Female, Male Female | 7 Participants | 18 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Male | 34 Participants | 102 Participants | 34 Participants | 34 Participants |
| Stroke Volume Index | 25.9 ml/m² STANDARD_DEVIATION 7.1 | 21.6 ml/m² STANDARD_DEVIATION 6.89 | 21.6 ml/m² STANDARD_DEVIATION 7.73 | 17.1 ml/m² STANDARD_DEVIATION 5.69 |
| Troponin (cTnT) | 34.2 ng/L STANDARD_DEVIATION 36.6 | 36.0 ng/L STANDARD_DEVIATION 53.6 | 33.5 ng/L STANDARD_DEVIATION 33.9 | 40.4 ng/L STANDARD_DEVIATION 78.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 41 | 2 / 40 |
| other Total, other adverse events | 23 / 39 | 31 / 41 | 33 / 40 |
| serious Total, serious adverse events | 2 / 39 | 2 / 41 | 6 / 40 |
Outcome results
Primary
Change in E/Ea Ratio
Change from baseline at 24 hours in the unitless ratio of E (cm/sec) to Ea (or e') (cm/sec) as measured by echocardiogram. The endpoint is the Tissue Doppler echocardiography showing measurement of mitral E/Ea ratio for assessment of diastolic dysfunction. Initially mitral E wave is measured. After that, color Tissue Doppler (tissue velocity imaging or TVI) mode is switched on to assess tissue Doppler. The cursor is placed over the medial mitral annulus and tissue Doppler tracing obtained. This allows Ea velocity to be measured. Higher values are suggestive of a worse outcome; less than 8 is normal.
Time frame: 24 hours
Population: Intent-to-Treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Change in E/Ea Ratio | -4.55 Unitless ratio |
| Placebo Cohort I | Change in E/Ea Ratio | -1.55 Unitless ratio |
| Istaroxime 1.0 µg/kg/Min | Change in E/Ea Ratio | -3.16 Unitless ratio |
| Placebo Cohort II | Change in E/Ea Ratio | -1.08 Unitless ratio |
Comparison: Null hypothesis: No difference in E/Ea ratio between istaroxime and placebop-value: 0.02995% CI: [-5.68, -0.32]ANOVA
Comparison: Null hypothesis: No difference in E/Ea ratio between istaroxime and placebop-value: 0.00995% CI: [-3.61, -0.55]ANOVA
Secondary
Change in Dyspnea
Measured using a visual analog scale (0 to 100). Higher scores indicate less dyspnea.
Time frame: 24 hours
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Change in Dyspnea | 9.75 Score on a scale (Visual Analog Scale) | Standard Deviation 11.8 |
| Placebo Cohort I | Change in Dyspnea | 9.14 Score on a scale (Visual Analog Scale) | Standard Deviation 10.08 |
| Istaroxime 1.0 µg/kg/Min | Change in Dyspnea | 12.09 Score on a scale (Visual Analog Scale) | Standard Deviation 14.79 |
Comparison: Null hypothesis: no difference between treatment groupsp-value: 0.98795% CI: [-5.216, 5.133]Mixed Models Analysis
Comparison: Null hypothesis: no difference between treatment groups.p-value: 0.25195% CI: [-2.168, 8.198]Mixed Models Analysis
Secondary
Change in E/A Ratio
Change from baseline at 24 hours in E/A ratio by tissue Doppler
Time frame: 24 hours
Population: Intent-to-Treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Change in E/A Ratio | -0.643 Unitless ratio |
| Placebo Cohort I | Change in E/A Ratio | 0.133 Unitless ratio |
| Istaroxime 1.0 µg/kg/Min | Change in E/A Ratio | -0.654 Unitless ratio |
| Placebo Cohort II | Change in E/A Ratio | 0.175 Unitless ratio |
Comparison: Null hypothesis: No difference in E to A ratio between istaroxime and placebo participants.p-value: 0.04295% CI: [-1.522, -0.032]ANOVA
Comparison: Null hypothesis: No difference in E to A ratio between istaroxime and placebo participants.p-value: 0.02995% CI: [-1.568, -0.091]ANOVA
Secondary
Change in LVEF
Change from baseline at 24 hours in LV ejection fraction (LVEF) by tissue Doppler
Time frame: 24 hours
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Change in LVEF | 3.026 % of blood leaving the heart |
| Placebo Cohort I | Change in LVEF | 1.263 % of blood leaving the heart |
| Istaroxime 1.0 µg/kg/Min | Change in LVEF | 3.818 % of blood leaving the heart |
| Placebo Cohort II | Change in LVEF | 2.833 % of blood leaving the heart |
Comparison: Null hypothesis: No difference in LVEF % between istaroxime and placebo participants.p-value: 0.08995% CI: [-0.2751, 3.8014]ANOVA
Comparison: Null hypothesis: No difference in LVEF % between istaroxime and placebo participants.p-value: 0.42395% CI: [-1.4668, 3.4365]ANOVA
Secondary
Change in LV End Diastolic Volume
Change from baseline in left ventricular end diastolic volume (LVEDV) by tissue Doppler
Time frame: 24 hours
Population: Intent-to-Treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Change in LV End Diastolic Volume | -0.710 mL |
| Placebo Cohort I | Change in LV End Diastolic Volume | 0.947 mL |
| Istaroxime 1.0 µg/kg/Min | Change in LV End Diastolic Volume | -3.666 mL |
| Placebo Cohort II | Change in LV End Diastolic Volume | -7.611 mL |
Comparison: Null hypothesis: No difference in E to A ratio between istaroxime and placebo participants.p-value: 0.58995% CI: [-7.777, 4.461]ANOVA
Comparison: Null hypothesis: No difference in E to A ratio between istaroxime and placebo participants.p-value: 0.42495% CI: [-5.886, 13.774]ANOVA
Secondary
Change in LV End Systolic Volume
Change from baseline in left ventricular end systolic volume (LVESV) by tissue Doppler
Time frame: 24 hours
Population: Intent-to-Treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Change in LV End Systolic Volume | -7.105 mL |
| Placebo Cohort I | Change in LV End Systolic Volume | -1.736 mL |
| Istaroxime 1.0 µg/kg/Min | Change in LV End Systolic Volume | -11.39 mL |
| Placebo Cohort II | Change in LV End Systolic Volume | -11.83 mL |
Comparison: Null hypothesis: No difference in LVESV between istaroxime and placebo participants.p-value: 0.1195% CI: [-11.999, 1.262]ANOVA
Comparison: Null hypothesis: No difference in LVEDV between istaroxime and placebo participants.p-value: 0.93195% CI: [-9.735, 10.614]ANOVA
Secondary
Change in SVI
Change from baseline at 24 hours in stroke volume index (SVI) by tissue Doppler
Time frame: 24 hours
Population: Intent-to-Treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Change in SVI | 5.334 mL/m² |
| Placebo Cohort I | Change in SVI | 1.649 mL/m² |
| Istaroxime 1.0 µg/kg/Min | Change in SVI | 5.488 mL/m² |
| Placebo Cohort II | Change in SVI | 3.178 mL/m² |
Comparison: Null hypothesis: No difference in SVI between istaroxime and placebo participants.p-value: 0.03495% CI: [0.285, 7.083]ANOVA
Comparison: Null hypothesis: No difference in E to A ratio between istaroxime and placebo participants.p-value: 0.0995% CI: [-0.373, 4.992]ANOVA
Other Pre-specified
All-Cause Mortality at Day 30
Safety endpoint: Mortality at Day 30
Time frame: 30 days
Population: Intent-to-Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Istaroxime 0.5 µg/kg/Min | All-Cause Mortality at Day 30 | 0 Participants |
| Placebo Cohort I | All-Cause Mortality at Day 30 | 0 Participants |
| Istaroxime 1.0 µg/kg/Min | All-Cause Mortality at Day 30 | 2 Participants |
Other Pre-specified
ALT - Shift
Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in alanine aminotransferase (ALT)
Time frame: Day 3
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | ALT - Shift | Abnormal to Abnormal | 4 Participants |
| Istaroxime 0.5 µg/kg/Min | ALT - Shift | Abnormal to Normal | 2 Participants |
| Istaroxime 0.5 µg/kg/Min | ALT - Shift | Normal to Normal | 29 Participants |
| Istaroxime 0.5 µg/kg/Min | ALT - Shift | Normal to Abnormal | 1 Participants |
| Istaroxime 0.5 µg/kg/Min | ALT - Shift | Missing | 3 Participants |
| Placebo Cohort I | ALT - Shift | Abnormal to Normal | 1 Participants |
| Placebo Cohort I | ALT - Shift | Normal to Normal | 31 Participants |
| Placebo Cohort I | ALT - Shift | Normal to Abnormal | 1 Participants |
| Placebo Cohort I | ALT - Shift | Abnormal to Abnormal | 5 Participants |
| Placebo Cohort I | ALT - Shift | Missing | 3 Participants |
| Istaroxime 1.0 µg/kg/Min | ALT - Shift | Missing | 4 Participants |
| Istaroxime 1.0 µg/kg/Min | ALT - Shift | Abnormal to Abnormal | 5 Participants |
| Istaroxime 1.0 µg/kg/Min | ALT - Shift | Normal to Normal | 29 Participants |
| Istaroxime 1.0 µg/kg/Min | ALT - Shift | Abnormal to Normal | 0 Participants |
| Istaroxime 1.0 µg/kg/Min | ALT - Shift | Normal to Abnormal | 2 Participants |
Other Pre-specified
AST - Shift
Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in aspartate aminotransferase (AST)
Time frame: Day 3
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | AST - Shift | Abnormal to Abnormal | 4 Participants |
| Istaroxime 0.5 µg/kg/Min | AST - Shift | Abnormal to Normal | 3 Participants |
| Istaroxime 0.5 µg/kg/Min | AST - Shift | Normal to Normal | 28 Participants |
| Istaroxime 0.5 µg/kg/Min | AST - Shift | Normal to Abnormal | 1 Participants |
| Istaroxime 0.5 µg/kg/Min | AST - Shift | Missing | 3 Participants |
| Placebo Cohort I | AST - Shift | Abnormal to Normal | 1 Participants |
| Placebo Cohort I | AST - Shift | Normal to Normal | 28 Participants |
| Placebo Cohort I | AST - Shift | Normal to Abnormal | 4 Participants |
| Placebo Cohort I | AST - Shift | Abnormal to Abnormal | 4 Participants |
| Placebo Cohort I | AST - Shift | Missing | 4 Participants |
| Istaroxime 1.0 µg/kg/Min | AST - Shift | Missing | 4 Participants |
| Istaroxime 1.0 µg/kg/Min | AST - Shift | Abnormal to Abnormal | 3 Participants |
| Istaroxime 1.0 µg/kg/Min | AST - Shift | Normal to Normal | 24 Participants |
| Istaroxime 1.0 µg/kg/Min | AST - Shift | Abnormal to Normal | 4 Participants |
| Istaroxime 1.0 µg/kg/Min | AST - Shift | Normal to Abnormal | 5 Participants |
Other Pre-specified
BUN - Shift
Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in blood urea nitrogen (BUN)
Time frame: Day 3
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | BUN - Shift | Abnormal to Normal | 3 Participants |
| Istaroxime 0.5 µg/kg/Min | BUN - Shift | Missing | 4 Participants |
| Istaroxime 0.5 µg/kg/Min | BUN - Shift | Normal to Normal | 11 Participants |
| Istaroxime 0.5 µg/kg/Min | BUN - Shift | Normal to Abnormal | 7 Participants |
| Istaroxime 0.5 µg/kg/Min | BUN - Shift | Abnormal to Abnormal | 14 Participants |
| Placebo Cohort I | BUN - Shift | Normal to Normal | 13 Participants |
| Placebo Cohort I | BUN - Shift | Abnormal to Normal | 2 Participants |
| Placebo Cohort I | BUN - Shift | Abnormal to Abnormal | 16 Participants |
| Placebo Cohort I | BUN - Shift | Missing | 6 Participants |
| Placebo Cohort I | BUN - Shift | Normal to Abnormal | 4 Participants |
| Istaroxime 1.0 µg/kg/Min | BUN - Shift | Missing | 5 Participants |
| Istaroxime 1.0 µg/kg/Min | BUN - Shift | Abnormal to Abnormal | 7 Participants |
| Istaroxime 1.0 µg/kg/Min | BUN - Shift | Normal to Normal | 14 Participants |
| Istaroxime 1.0 µg/kg/Min | BUN - Shift | Normal to Abnormal | 6 Participants |
| Istaroxime 1.0 µg/kg/Min | BUN - Shift | Abnormal to Normal | 8 Participants |
Other Pre-specified
Calcium - Shift
Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in calcium
Time frame: Day 3
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Calcium - Shift | Abnormal to Abnormal | 3 Participants |
| Istaroxime 0.5 µg/kg/Min | Calcium - Shift | Abnormal to Normal | 3 Participants |
| Istaroxime 0.5 µg/kg/Min | Calcium - Shift | Normal to Normal | 24 Participants |
| Istaroxime 0.5 µg/kg/Min | Calcium - Shift | Normal to Abnormal | 4 Participants |
| Istaroxime 0.5 µg/kg/Min | Calcium - Shift | Missing | 5 Participants |
| Placebo Cohort I | Calcium - Shift | Abnormal to Normal | 2 Participants |
| Placebo Cohort I | Calcium - Shift | Normal to Normal | 26 Participants |
| Placebo Cohort I | Calcium - Shift | Normal to Abnormal | 2 Participants |
| Placebo Cohort I | Calcium - Shift | Abnormal to Abnormal | 1 Participants |
| Placebo Cohort I | Calcium - Shift | Missing | 10 Participants |
| Istaroxime 1.0 µg/kg/Min | Calcium - Shift | Missing | 6 Participants |
| Istaroxime 1.0 µg/kg/Min | Calcium - Shift | Abnormal to Abnormal | 4 Participants |
| Istaroxime 1.0 µg/kg/Min | Calcium - Shift | Normal to Normal | 20 Participants |
| Istaroxime 1.0 µg/kg/Min | Calcium - Shift | Abnormal to Normal | 9 Participants |
| Istaroxime 1.0 µg/kg/Min | Calcium - Shift | Normal to Abnormal | 1 Participants |
Other Pre-specified
Change in cTnT
Safety endpoint: Changes in troponin (cTnT)
Time frame: 24 hours
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Change in cTnT | 0.23 ng/L | Standard Deviation 10.83 |
| Placebo Cohort I | Change in cTnT | 0.51 ng/L | Standard Deviation 7.58 |
| Istaroxime 1.0 µg/kg/Min | Change in cTnT | -4.06 ng/L | Standard Deviation 49.97 |
Other Pre-specified
Change in eGFR
Safety endpoint: Change from baseline in estimated glomerular filtration rate (eGFR)
Time frame: 24 Hours
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Change in eGFR | -0.60 ml/min/1.73·m² | Standard Deviation 14.71 |
| Placebo Cohort I | Change in eGFR | 5.19 ml/min/1.73·m² | Standard Deviation 16.25 |
| Istaroxime 1.0 µg/kg/Min | Change in eGFR | 7.65 ml/min/1.73·m² | Standard Deviation 13.22 |
Other Pre-specified
Hematocrit - Shift
Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in hematocrit
Time frame: Day 3
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Hematocrit - Shift | Abnormal to Abnormal | 6 Participants |
| Istaroxime 0.5 µg/kg/Min | Hematocrit - Shift | Abnormal to Normal | 3 Participants |
| Istaroxime 0.5 µg/kg/Min | Hematocrit - Shift | Normal to Normal | 21 Participants |
| Istaroxime 0.5 µg/kg/Min | Hematocrit - Shift | Normal to Abnormal | 7 Participants |
| Istaroxime 0.5 µg/kg/Min | Hematocrit - Shift | Missing | 2 Participants |
| Placebo Cohort I | Hematocrit - Shift | Abnormal to Normal | 7 Participants |
| Placebo Cohort I | Hematocrit - Shift | Normal to Normal | 15 Participants |
| Placebo Cohort I | Hematocrit - Shift | Normal to Abnormal | 3 Participants |
| Placebo Cohort I | Hematocrit - Shift | Abnormal to Abnormal | 14 Participants |
| Placebo Cohort I | Hematocrit - Shift | Missing | 2 Participants |
| Istaroxime 1.0 µg/kg/Min | Hematocrit - Shift | Missing | 4 Participants |
| Istaroxime 1.0 µg/kg/Min | Hematocrit - Shift | Abnormal to Abnormal | 8 Participants |
| Istaroxime 1.0 µg/kg/Min | Hematocrit - Shift | Normal to Normal | 17 Participants |
| Istaroxime 1.0 µg/kg/Min | Hematocrit - Shift | Abnormal to Normal | 6 Participants |
| Istaroxime 1.0 µg/kg/Min | Hematocrit - Shift | Normal to Abnormal | 5 Participants |
Other Pre-specified
Hemoglobin - Shift
Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in hemoglobin
Time frame: Day 3
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Hemoglobin - Shift | Abnormal to Normal | 1 Participants |
| Istaroxime 0.5 µg/kg/Min | Hemoglobin - Shift | Normal to Abnormal | 5 Participants |
| Istaroxime 0.5 µg/kg/Min | Hemoglobin - Shift | Abnormal to Abnormal | 8 Participants |
| Istaroxime 0.5 µg/kg/Min | Hemoglobin - Shift | Normal to Normal | 23 Participants |
| Istaroxime 0.5 µg/kg/Min | Hemoglobin - Shift | Missing | 2 Participants |
| Placebo Cohort I | Hemoglobin - Shift | Normal to Normal | 13 Participants |
| Placebo Cohort I | Hemoglobin - Shift | Normal to Abnormal | 3 Participants |
| Placebo Cohort I | Hemoglobin - Shift | Abnormal to Normal | 7 Participants |
| Placebo Cohort I | Hemoglobin - Shift | Abnormal to Abnormal | 16 Participants |
| Placebo Cohort I | Hemoglobin - Shift | Missing | 2 Participants |
| Istaroxime 1.0 µg/kg/Min | Hemoglobin - Shift | Abnormal to Abnormal | 6 Participants |
| Istaroxime 1.0 µg/kg/Min | Hemoglobin - Shift | Normal to Abnormal | 2 Participants |
| Istaroxime 1.0 µg/kg/Min | Hemoglobin - Shift | Normal to Normal | 23 Participants |
| Istaroxime 1.0 µg/kg/Min | Hemoglobin - Shift | Abnormal to Normal | 5 Participants |
| Istaroxime 1.0 µg/kg/Min | Hemoglobin - Shift | Missing | 4 Participants |
Other Pre-specified
Participants With Clinically or Hemodynamically Significant Episodes of Arrhythmias
Safety endpoint: Number of participants with incidence of clinically or hemodynamically significant episodes of supraventricular or ventricular arrhythmias detected by continuous ECG dynamic monitoring
Time frame: 24 hours
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Participants With Clinically or Hemodynamically Significant Episodes of Arrhythmias | 6 Participants |
| Placebo Cohort I | Participants With Clinically or Hemodynamically Significant Episodes of Arrhythmias | 1 Participants |
| Istaroxime 1.0 µg/kg/Min | Participants With Clinically or Hemodynamically Significant Episodes of Arrhythmias | 4 Participants |
Other Pre-specified
Platelets - Shift
Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in platelets
Time frame: Day 3
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Platelets - Shift | Abnormal to Abnormal | 4 Participants |
| Istaroxime 0.5 µg/kg/Min | Platelets - Shift | Abnormal to Normal | 4 Participants |
| Istaroxime 0.5 µg/kg/Min | Platelets - Shift | Normal to Normal | 26 Participants |
| Istaroxime 0.5 µg/kg/Min | Platelets - Shift | Normal to Abnormal | 3 Participants |
| Istaroxime 0.5 µg/kg/Min | Platelets - Shift | Missing | 2 Participants |
| Placebo Cohort I | Platelets - Shift | Abnormal to Normal | 1 Participants |
| Placebo Cohort I | Platelets - Shift | Normal to Normal | 32 Participants |
| Placebo Cohort I | Platelets - Shift | Normal to Abnormal | 2 Participants |
| Placebo Cohort I | Platelets - Shift | Abnormal to Abnormal | 3 Participants |
| Placebo Cohort I | Platelets - Shift | Missing | 3 Participants |
| Istaroxime 1.0 µg/kg/Min | Platelets - Shift | Missing | 4 Participants |
| Istaroxime 1.0 µg/kg/Min | Platelets - Shift | Abnormal to Abnormal | 1 Participants |
| Istaroxime 1.0 µg/kg/Min | Platelets - Shift | Normal to Normal | 31 Participants |
| Istaroxime 1.0 µg/kg/Min | Platelets - Shift | Abnormal to Normal | 0 Participants |
| Istaroxime 1.0 µg/kg/Min | Platelets - Shift | Normal to Abnormal | 4 Participants |
Other Pre-specified
Potassium - Shift
Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in potassium
Time frame: Day 3
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Potassium - Shift | Missing | 1 Participants |
| Istaroxime 0.5 µg/kg/Min | Potassium - Shift | Normal to Normal | 37 Participants |
| Istaroxime 0.5 µg/kg/Min | Potassium - Shift | Normal to Abnormal | 1 Participants |
| Istaroxime 0.5 µg/kg/Min | Potassium - Shift | Abnormal to Normal | 0 Participants |
| Istaroxime 0.5 µg/kg/Min | Potassium - Shift | Abnormal to Abnormal | 0 Participants |
| Placebo Cohort I | Potassium - Shift | Abnormal to Normal | 0 Participants |
| Placebo Cohort I | Potassium - Shift | Abnormal to Abnormal | 0 Participants |
| Placebo Cohort I | Potassium - Shift | Normal to Normal | 40 Participants |
| Placebo Cohort I | Potassium - Shift | Missing | 1 Participants |
| Placebo Cohort I | Potassium - Shift | Normal to Abnormal | 0 Participants |
| Istaroxime 1.0 µg/kg/Min | Potassium - Shift | Abnormal to Abnormal | 0 Participants |
| Istaroxime 1.0 µg/kg/Min | Potassium - Shift | Normal to Abnormal | 2 Participants |
| Istaroxime 1.0 µg/kg/Min | Potassium - Shift | Abnormal to Normal | 0 Participants |
| Istaroxime 1.0 µg/kg/Min | Potassium - Shift | Missing | 4 Participants |
| Istaroxime 1.0 µg/kg/Min | Potassium - Shift | Normal to Normal | 34 Participants |
Other Pre-specified
PR Interval
Safety Endpoint: The PR interval, measured in milliseconds, extends from the beginning of the P wave (the onset of atrial depolarization) until the beginning of the QRS complex (the onset of ventricular depolarization).
Time frame: 24 Hours
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | PR Interval | 184.0 msec | Standard Deviation 31.27 |
| Placebo Cohort I | PR Interval | 179.2 msec | Standard Deviation 28.11 |
| Istaroxime 1.0 µg/kg/Min | PR Interval | 169.41 msec | Standard Deviation 32.72 |
Other Pre-specified
QRS Duration
Safety endpoint: The quasi-random signal (QRS) duration represents the time for ventricular depolarization, normally 0.06 to 0.10 seconds.
Time frame: 24 hours
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | QRS Duration | 125.2 msec | Standard Deviation 37.11 |
| Placebo Cohort I | QRS Duration | 132.5 msec | Standard Deviation 31.59 |
| Istaroxime 1.0 µg/kg/Min | QRS Duration | 127.6 msec | Standard Deviation 26.65 |
Other Pre-specified
QTc Interval
Safety Endpoint: The corrected QT interval (QTc) on an ECG represents the duration in milliseconds of the ventricular action potential, which physiologically correlates with the duration of the ventricular depolarization and repolarization.
Time frame: 24 Hours
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | QTc Interval | 472.8 msec | Standard Deviation 41.9 |
| Placebo Cohort I | QTc Interval | 480.8 msec | Standard Deviation 55.72 |
| Istaroxime 1.0 µg/kg/Min | QTc Interval | 486.9 msec | Standard Deviation 40.18 |
Other Pre-specified
RBC - Shift
Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in red blood cells (RBC)
Time frame: Day 3
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | RBC - Shift | Abnormal to Abnormal | 8 Participants |
| Istaroxime 0.5 µg/kg/Min | RBC - Shift | Abnormal to Normal | 2 Participants |
| Istaroxime 0.5 µg/kg/Min | RBC - Shift | Normal to Normal | 22 Participants |
| Istaroxime 0.5 µg/kg/Min | RBC - Shift | Normal to Abnormal | 5 Participants |
| Istaroxime 0.5 µg/kg/Min | RBC - Shift | Missing | 2 Participants |
| Placebo Cohort I | RBC - Shift | Abnormal to Normal | 3 Participants |
| Placebo Cohort I | RBC - Shift | Normal to Normal | 17 Participants |
| Placebo Cohort I | RBC - Shift | Normal to Abnormal | 3 Participants |
| Placebo Cohort I | RBC - Shift | Abnormal to Abnormal | 16 Participants |
| Placebo Cohort I | RBC - Shift | Missing | 2 Participants |
| Istaroxime 1.0 µg/kg/Min | RBC - Shift | Missing | 4 Participants |
| Istaroxime 1.0 µg/kg/Min | RBC - Shift | Abnormal to Abnormal | 7 Participants |
| Istaroxime 1.0 µg/kg/Min | RBC - Shift | Normal to Normal | 21 Participants |
| Istaroxime 1.0 µg/kg/Min | RBC - Shift | Abnormal to Normal | 4 Participants |
| Istaroxime 1.0 µg/kg/Min | RBC - Shift | Normal to Abnormal | 4 Participants |
Other Pre-specified
Sodium - Shift
Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in sodium
Time frame: Day 3
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Sodium - Shift | Abnormal to Abnormal | 2 Participants |
| Istaroxime 0.5 µg/kg/Min | Sodium - Shift | Abnormal to Normal | 4 Participants |
| Istaroxime 0.5 µg/kg/Min | Sodium - Shift | Normal to Normal | 23 Participants |
| Istaroxime 0.5 µg/kg/Min | Sodium - Shift | Normal to Abnormal | 9 Participants |
| Istaroxime 0.5 µg/kg/Min | Sodium - Shift | Missing | 1 Participants |
| Placebo Cohort I | Sodium - Shift | Abnormal to Normal | 2 Participants |
| Placebo Cohort I | Sodium - Shift | Normal to Normal | 21 Participants |
| Placebo Cohort I | Sodium - Shift | Normal to Abnormal | 12 Participants |
| Placebo Cohort I | Sodium - Shift | Abnormal to Abnormal | 5 Participants |
| Placebo Cohort I | Sodium - Shift | Missing | 1 Participants |
| Istaroxime 1.0 µg/kg/Min | Sodium - Shift | Missing | 4 Participants |
| Istaroxime 1.0 µg/kg/Min | Sodium - Shift | Abnormal to Abnormal | 8 Participants |
| Istaroxime 1.0 µg/kg/Min | Sodium - Shift | Normal to Normal | 19 Participants |
| Istaroxime 1.0 µg/kg/Min | Sodium - Shift | Abnormal to Normal | 1 Participants |
| Istaroxime 1.0 µg/kg/Min | Sodium - Shift | Normal to Abnormal | 8 Participants |
Other Pre-specified
Total Bilirubin - Shift
Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in total bilirubin
Time frame: Day 3
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | Total Bilirubin - Shift | Normal to Abnormal | 3 Participants |
| Istaroxime 0.5 µg/kg/Min | Total Bilirubin - Shift | Abnormal to Abnormal | 13 Participants |
| Istaroxime 0.5 µg/kg/Min | Total Bilirubin - Shift | Normal to Normal | 9 Participants |
| Istaroxime 0.5 µg/kg/Min | Total Bilirubin - Shift | Abnormal to Normal | 9 Participants |
| Istaroxime 0.5 µg/kg/Min | Total Bilirubin - Shift | Missing | 5 Participants |
| Placebo Cohort I | Total Bilirubin - Shift | Abnormal to Normal | 3 Participants |
| Placebo Cohort I | Total Bilirubin - Shift | Abnormal to Abnormal | 11 Participants |
| Placebo Cohort I | Total Bilirubin - Shift | Missing | 4 Participants |
| Placebo Cohort I | Total Bilirubin - Shift | Normal to Abnormal | 2 Participants |
| Placebo Cohort I | Total Bilirubin - Shift | Normal to Normal | 21 Participants |
| Istaroxime 1.0 µg/kg/Min | Total Bilirubin - Shift | Missing | 4 Participants |
| Istaroxime 1.0 µg/kg/Min | Total Bilirubin - Shift | Normal to Normal | 13 Participants |
| Istaroxime 1.0 µg/kg/Min | Total Bilirubin - Shift | Normal to Abnormal | 2 Participants |
| Istaroxime 1.0 µg/kg/Min | Total Bilirubin - Shift | Abnormal to Normal | 6 Participants |
| Istaroxime 1.0 µg/kg/Min | Total Bilirubin - Shift | Abnormal to Abnormal | 15 Participants |
Other Pre-specified
White Blood Cells (WBC) - Shift
Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in WBC
Time frame: Day 3
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Istaroxime 0.5 µg/kg/Min | White Blood Cells (WBC) - Shift | Normal to Abnormal | 2 Participants |
| Istaroxime 0.5 µg/kg/Min | White Blood Cells (WBC) - Shift | Abnormal to Abnormal | 0 Participants |
| Istaroxime 0.5 µg/kg/Min | White Blood Cells (WBC) - Shift | Normal to Normal | 35 Participants |
| Istaroxime 0.5 µg/kg/Min | White Blood Cells (WBC) - Shift | Abnormal to Normal | 0 Participants |
| Istaroxime 0.5 µg/kg/Min | White Blood Cells (WBC) - Shift | Missing | 2 Participants |
| Placebo Cohort I | White Blood Cells (WBC) - Shift | Abnormal to Normal | 1 Participants |
| Placebo Cohort I | White Blood Cells (WBC) - Shift | Abnormal to Abnormal | 2 Participants |
| Placebo Cohort I | White Blood Cells (WBC) - Shift | Missing | 2 Participants |
| Placebo Cohort I | White Blood Cells (WBC) - Shift | Normal to Abnormal | 6 Participants |
| Placebo Cohort I | White Blood Cells (WBC) - Shift | Normal to Normal | 30 Participants |
| Istaroxime 1.0 µg/kg/Min | White Blood Cells (WBC) - Shift | Normal to Abnormal | 6 Participants |
| Istaroxime 1.0 µg/kg/Min | White Blood Cells (WBC) - Shift | Normal to Normal | 25 Participants |
| Istaroxime 1.0 µg/kg/Min | White Blood Cells (WBC) - Shift | Missing | 4 Participants |
| Istaroxime 1.0 µg/kg/Min | White Blood Cells (WBC) - Shift | Abnormal to Normal | 2 Participants |
| Istaroxime 1.0 µg/kg/Min | White Blood Cells (WBC) - Shift | Abnormal to Abnormal | 3 Participants |