Trial Outcomes & Findings for The Clinical Study of the Safety and Efficacy of Istaroxime in Treatment of Acute Decompensated Heart Failure (NCT NCT02617446)

Last Updated: 2023-05-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

120 participants

Primary outcome timeframe

24 hours

Results posted on

2023-05-24

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Placebo IV infusion for 24 hours Placebo: IV of matching saline solution	Istaroxime 0.5 µg/kg/Min Istaroxime via IV infusion for 24 hours Istaroxime: IV infusion of istaroxime 0.5 µg/kg/min	Istaroxime 1.0 µg/kg/Min Istaroxime via IV infusion for 24 hours Istaroxime: IV infusion of istaroxime 1.0 µg/kg/min
Overall Study STARTED	39	41	40
Overall Study COMPLETED	35	39	33
Overall Study NOT COMPLETED	4	2	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo IV infusion for 24 hours Placebo: IV of matching saline solution	Istaroxime 0.5 µg/kg/Min Istaroxime via IV infusion for 24 hours Istaroxime: IV infusion of istaroxime 0.5 µg/kg/min	Istaroxime 1.0 µg/kg/Min Istaroxime via IV infusion for 24 hours Istaroxime: IV infusion of istaroxime 1.0 µg/kg/min
Overall Study Withdrawal by Subject	0	2	0
Overall Study Adverse Event	1	0	5
Overall Study Lost to Follow-up	3	0	0
Overall Study Death	0	0	2

Baseline Characteristics

Measurements for 1 istaroxime 0.5 µg/kg/min participant not recorded (missing).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=39 Participants IV infusion for 24 hours Placebo: IV of matching saline solution	Istaroxime 0.5 µg/kg/Min n=41 Participants Istaroxime via IV infusion for 24 hours Istaroxime: IV infusion of istaroxime 0.5 µg/kg/min	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime via IV infusion for 24 hours Istaroxime: IV infusion of istaroxime 1.0 µg/kg/min	Total n=120 Participants Total of all reporting groups
Age, Continuous	56.67 years STANDARD_DEVIATION 16.21 • n=39 Participants	59.73 years STANDARD_DEVIATION 15.53 • n=41 Participants	52.23 years STANDARD_DEVIATION 13.02 • n=40 Participants	56.24 years STANDARD_DEVIATION 14.98 • n=120 Participants
Sex: Female, Male Female	5 Participants n=39 Participants	7 Participants n=41 Participants	6 Participants n=40 Participants	18 Participants n=120 Participants
Sex: Female, Male Male	34 Participants n=39 Participants	34 Participants n=41 Participants	34 Participants n=40 Participants	102 Participants n=120 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=40 Participants	0 Participants n=120 Participants
Race (NIH/OMB) Asian	32 Participants n=39 Participants	24 Participants n=41 Participants	40 Participants n=40 Participants	96 Participants n=120 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=40 Participants	0 Participants n=120 Participants
Race (NIH/OMB) Black or African American	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=40 Participants	0 Participants n=120 Participants
Race (NIH/OMB) White	7 Participants n=39 Participants	17 Participants n=41 Participants	0 Participants n=40 Participants	24 Participants n=120 Participants
Race (NIH/OMB) More than one race	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=40 Participants	0 Participants n=120 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=40 Participants	0 Participants n=120 Participants
Region of Enrollment China	32 participants n=39 Participants	24 participants n=41 Participants	40 participants n=40 Participants	96 participants n=120 Participants
Region of Enrollment Italy	7 participants n=39 Participants	17 participants n=41 Participants	0 participants n=40 Participants	24 participants n=120 Participants
E/Ea Ratio	17.0 Unitless ratio STANDARD_DEVIATION 5.33 • n=39 Participants • Measurements for 1 istaroxime 0.5 µg/kg/min participant not recorded (missing).	20.4 Unitless ratio STANDARD_DEVIATION 7.87 • n=40 Participants • Measurements for 1 istaroxime 0.5 µg/kg/min participant not recorded (missing).	15.1 Unitless ratio STANDARD_DEVIATION 5.48 • n=40 Participants • Measurements for 1 istaroxime 0.5 µg/kg/min participant not recorded (missing).	17.5 Unitless ratio STANDARD_DEVIATION 6.36 • n=119 Participants • Measurements for 1 istaroxime 0.5 µg/kg/min participant not recorded (missing).
Left ventricular ejection fraction (LVEF)	26.2 % of blood in heart pumped STANDARD_DEVIATION 7.4 • n=38 Participants • Measurements for 4 participants (1 placebo participant, 1 istaroxime 0.5 µg/kg/min participant, 2 istaroxime 1.0 µg/kg/min participants) not recorded (missing)	27.4 % of blood in heart pumped STANDARD_DEVIATION 6.7 • n=40 Participants • Measurements for 4 participants (1 placebo participant, 1 istaroxime 0.5 µg/kg/min participant, 2 istaroxime 1.0 µg/kg/min participants) not recorded (missing)	28.7 % of blood in heart pumped STANDARD_DEVIATION 7.2 • n=38 Participants • Measurements for 4 participants (1 placebo participant, 1 istaroxime 0.5 µg/kg/min participant, 2 istaroxime 1.0 µg/kg/min participants) not recorded (missing)	27.4 % of blood in heart pumped STANDARD_DEVIATION 7.1 • n=116 Participants • Measurements for 4 participants (1 placebo participant, 1 istaroxime 0.5 µg/kg/min participant, 2 istaroxime 1.0 µg/kg/min participants) not recorded (missing)
Stroke Volume Index	21.6 ml/m² STANDARD_DEVIATION 7.73 • n=39 Participants • Measurements for 2 participants (1 istaroxime 0.5 µg/kg/min participant, 1 istaroxime 1.0 µg/kg/min participant) not recorded (missing)	25.9 ml/m² STANDARD_DEVIATION 7.10 • n=40 Participants • Measurements for 2 participants (1 istaroxime 0.5 µg/kg/min participant, 1 istaroxime 1.0 µg/kg/min participant) not recorded (missing)	17.1 ml/m² STANDARD_DEVIATION 5.69 • n=39 Participants • Measurements for 2 participants (1 istaroxime 0.5 µg/kg/min participant, 1 istaroxime 1.0 µg/kg/min participant) not recorded (missing)	21.6 ml/m² STANDARD_DEVIATION 6.89 • n=118 Participants • Measurements for 2 participants (1 istaroxime 0.5 µg/kg/min participant, 1 istaroxime 1.0 µg/kg/min participant) not recorded (missing)
Dyspnea	70.8 Scores on a scale STANDARD_DEVIATION 21.32 • n=39 Participants	73.6 Scores on a scale STANDARD_DEVIATION 19.49 • n=41 Participants	71.5 Scores on a scale STANDARD_DEVIATION 20.95 • n=40 Participants	72.0 Scores on a scale STANDARD_DEVIATION 20.59 • n=120 Participants
Troponin (cTnT)	33.5 ng/L STANDARD_DEVIATION 33.9 • n=39 Participants	34.2 ng/L STANDARD_DEVIATION 36.6 • n=41 Participants	40.4 ng/L STANDARD_DEVIATION 78.3 • n=40 Participants	36.0 ng/L STANDARD_DEVIATION 53.6 • n=120 Participants
eGFR	78.1 ml/min/1.73·m² STANDARD_DEVIATION 38.33 • n=39 Participants • Measurements for 1 istaroxime 0.5 µg/kg/min participant not recorded (missing)	72.3 ml/min/1.73·m² STANDARD_DEVIATION 30.93 • n=40 Participants • Measurements for 1 istaroxime 0.5 µg/kg/min participant not recorded (missing)	81.3 ml/min/1.73·m² STANDARD_DEVIATION 27.01 • n=40 Participants • Measurements for 1 istaroxime 0.5 µg/kg/min participant not recorded (missing)	77.2 ml/min/1.73·m² STANDARD_DEVIATION 32.36 • n=119 Participants • Measurements for 1 istaroxime 0.5 µg/kg/min participant not recorded (missing)

PRIMARY outcome

Timeframe: 24 hours

Population: Intent-to-Treat

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=41 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=19 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II n=20 Participants Placebo participants enrolled in Cohort II
Change in E/Ea Ratio	-4.55 Unitless ratio Interval -6.05 to -3.04	-1.55 Unitless ratio Interval -3.77 to 0.67	-3.16 Unitless ratio Interval -4.09 to -2.24	-1.08 Unitless ratio Interval -2.3 to 0.13

SECONDARY outcome

Timeframe: 24 hours

Population: Intent-to-Treat

Change from baseline at 24 hours in LV ejection fraction (LVEF) by tissue Doppler

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=41 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=19 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II n=20 Participants Placebo participants enrolled in Cohort II
Change in LVEF	3.026 % of blood leaving the heart Interval 1.85 to 4.203	1.263 % of blood leaving the heart Interval -0.401 to 2.927	3.818 % of blood leaving the heart Interval 2.362 to 5.275	2.833 % of blood leaving the heart Interval 0.861 to 4.805

SECONDARY outcome

Timeframe: 24 hours

Population: Intent-to-Treat

Change from baseline at 24 hours in stroke volume index (SVI) by tissue Doppler

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=41 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=19 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II n=20 Participants Placebo participants enrolled in Cohort II
Change in SVI	5.334 mL/m² Interval 3.371 to 7.296	1.649 mL/m² Interval -1.126 to 4.425	5.488 mL/m² Interval 3.882 to 7.094	3.178 mL/m² Interval 1.03 to 5.327

SECONDARY outcome

Timeframe: 24 hours

Population: Intent-to-Treat

Change from baseline at 24 hours in E/A ratio by tissue Doppler

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=41 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=19 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II n=20 Participants Placebo participants enrolled in Cohort II
Change in E/A Ratio	-0.643 Unitless ratio Interval -1.091 to -0.197	0.133 Unitless ratio Interval -0.463 to 0.729	-0.654 Unitless ratio Interval -1.093 to -0.216	0.175 Unitless ratio Interval -0.419 to 0.769

SECONDARY outcome

Timeframe: 24 hours

Population: Intent-to-Treat

Change from baseline in left ventricular end systolic volume (LVESV) by tissue Doppler

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=41 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=19 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II n=20 Participants Placebo participants enrolled in Cohort II
Change in LV End Systolic Volume	-7.105 mL Interval -10.933 to -3.277	-1.736 mL Interval -7.15 to 3.677	-11.39 mL Interval -17.438 to -5.35	-11.83 mL Interval -20.017 to -3.649

SECONDARY outcome

Timeframe: 24 hours

Population: Intent-to-Treat

Change from baseline in left ventricular end diastolic volume (LVEDV) by tissue Doppler

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=41 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=19 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II n=20 Participants Placebo participants enrolled in Cohort II
Change in LV End Diastolic Volume	-0.710 mL Interval -4.243 to 2.822	0.947 mL Interval -4.049 to 5.944	-3.666 mL Interval -9.507 to 2.173	-7.611 mL Interval -15.518 to 0.296

SECONDARY outcome

Timeframe: 24 hours

Population: Intent-to-Treat

Measured using a visual analog scale (0 to 100). Higher scores indicate less dyspnea.

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
Change in Dyspnea	9.75 Score on a scale (Visual Analog Scale) Standard Deviation 11.80	9.14 Score on a scale (Visual Analog Scale) Standard Deviation 10.08	12.09 Score on a scale (Visual Analog Scale) Standard Deviation 14.79	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Population: Intent-to-Treat

Safety endpoint: Changes in troponin (cTnT)

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
Change in cTnT	0.23 ng/L Standard Deviation 10.83	0.51 ng/L Standard Deviation 7.58	-4.06 ng/L Standard Deviation 49.97	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 Hours

Population: Safety Population

Safety endpoint: Change from baseline in estimated glomerular filtration rate (eGFR)

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
Change in eGFR	-0.60 ml/min/1.73·m² Standard Deviation 14.71	5.19 ml/min/1.73·m² Standard Deviation 16.25	7.65 ml/min/1.73·m² Standard Deviation 13.22	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Population: Safety Population

Safety endpoint: Number of participants with incidence of clinically or hemodynamically significant episodes of supraventricular or ventricular arrhythmias detected by continuous ECG dynamic monitoring

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
Participants With Clinically or Hemodynamically Significant Episodes of Arrhythmias	6 Participants	1 Participants	4 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 Hours

Population: Safety Population

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).

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
PR Interval	184.0 msec Standard Deviation 31.27	179.2 msec Standard Deviation 28.11	169.41 msec Standard Deviation 32.72	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Population: Safety Population

Safety endpoint: The quasi-random signal (QRS) duration represents the time for ventricular depolarization, normally 0.06 to 0.10 seconds.

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
QRS Duration	125.2 msec Standard Deviation 37.11	132.5 msec Standard Deviation 31.59	127.6 msec Standard Deviation 26.65	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 Hours

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
QTc Interval	472.8 msec Standard Deviation 41.90	480.8 msec Standard Deviation 55.72	486.9 msec Standard Deviation 40.18	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 30 days

Population: Intent-to-Treat

Safety endpoint: Mortality at Day 30

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
All-Cause Mortality at Day 30	0 Participants	0 Participants	2 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3

Population: Safety Population

Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in red blood cells (RBC)

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
RBC - Shift Normal to Normal	22 Participants	17 Participants	21 Participants	—
RBC - Shift Normal to Abnormal	5 Participants	3 Participants	4 Participants	—
RBC - Shift Abnormal to Normal	2 Participants	3 Participants	4 Participants	—
RBC - Shift Abnormal to Abnormal	8 Participants	16 Participants	7 Participants	—
RBC - Shift Missing	2 Participants	2 Participants	4 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3

Population: Safety Population

Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in hematocrit

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
Hematocrit - Shift Normal to Normal	21 Participants	15 Participants	17 Participants	—
Hematocrit - Shift Normal to Abnormal	7 Participants	3 Participants	5 Participants	—
Hematocrit - Shift Abnormal to Normal	3 Participants	7 Participants	6 Participants	—
Hematocrit - Shift Abnormal to Abnormal	6 Participants	14 Participants	8 Participants	—
Hematocrit - Shift Missing	2 Participants	2 Participants	4 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3

Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in hemoglobin

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
Hemoglobin - Shift Normal to Normal	23 Participants	13 Participants	23 Participants	—
Hemoglobin - Shift Normal to Abnormal	5 Participants	3 Participants	2 Participants	—
Hemoglobin - Shift Abnormal to Normal	1 Participants	7 Participants	5 Participants	—
Hemoglobin - Shift Abnormal to Abnormal	8 Participants	16 Participants	6 Participants	—
Hemoglobin - Shift Missing	2 Participants	2 Participants	4 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3

Population: Safety Population

Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in WBC

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
White Blood Cells (WBC) - Shift Normal to Normal	35 Participants	30 Participants	25 Participants	—
White Blood Cells (WBC) - Shift Normal to Abnormal	2 Participants	6 Participants	6 Participants	—
White Blood Cells (WBC) - Shift Abnormal to Normal	0 Participants	1 Participants	2 Participants	—
White Blood Cells (WBC) - Shift Abnormal to Abnormal	0 Participants	2 Participants	3 Participants	—
White Blood Cells (WBC) - Shift Missing	2 Participants	2 Participants	4 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3

Population: Safety Population

Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in platelets

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
Platelets - Shift Normal to Normal	26 Participants	32 Participants	31 Participants	—
Platelets - Shift Normal to Abnormal	3 Participants	2 Participants	4 Participants	—
Platelets - Shift Abnormal to Normal	4 Participants	1 Participants	0 Participants	—
Platelets - Shift Abnormal to Abnormal	4 Participants	3 Participants	1 Participants	—
Platelets - Shift Missing	2 Participants	3 Participants	4 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3

Population: Safety Population

Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in potassium

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
Potassium - Shift Normal to Normal	37 Participants	40 Participants	34 Participants	—
Potassium - Shift Normal to Abnormal	1 Participants	0 Participants	2 Participants	—
Potassium - Shift Abnormal to Normal	0 Participants	0 Participants	0 Participants	—
Potassium - Shift Abnormal to Abnormal	0 Participants	0 Participants	0 Participants	—
Potassium - Shift Missing	1 Participants	1 Participants	4 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3

Population: Safety Population

Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in sodium

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
Sodium - Shift Normal to Normal	23 Participants	21 Participants	19 Participants	—
Sodium - Shift Normal to Abnormal	9 Participants	12 Participants	8 Participants	—
Sodium - Shift Abnormal to Normal	4 Participants	2 Participants	1 Participants	—
Sodium - Shift Abnormal to Abnormal	2 Participants	5 Participants	8 Participants	—
Sodium - Shift Missing	1 Participants	1 Participants	4 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3

Population: Safety Population

Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in calcium

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
Calcium - Shift Missing	5 Participants	10 Participants	6 Participants	—
Calcium - Shift Normal to Normal	24 Participants	26 Participants	20 Participants	—
Calcium - Shift Normal to Abnormal	4 Participants	2 Participants	1 Participants	—
Calcium - Shift Abnormal to Normal	3 Participants	2 Participants	9 Participants	—
Calcium - Shift Abnormal to Abnormal	3 Participants	1 Participants	4 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3

Population: Safety Population

Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in blood urea nitrogen (BUN)

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
BUN - Shift Normal to Abnormal	7 Participants	4 Participants	6 Participants	—
BUN - Shift Abnormal to Normal	3 Participants	2 Participants	8 Participants	—
BUN - Shift Abnormal to Abnormal	14 Participants	16 Participants	7 Participants	—
BUN - Shift Missing	4 Participants	6 Participants	5 Participants	—
BUN - Shift Normal to Normal	11 Participants	13 Participants	14 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3

Population: Safety Population

Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in alanine aminotransferase (ALT)

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
ALT - Shift Normal to Normal	29 Participants	31 Participants	29 Participants	—
ALT - Shift Normal to Abnormal	1 Participants	1 Participants	2 Participants	—
ALT - Shift Abnormal to Normal	2 Participants	1 Participants	0 Participants	—
ALT - Shift Abnormal to Abnormal	4 Participants	5 Participants	5 Participants	—
ALT - Shift Missing	3 Participants	3 Participants	4 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3

Population: Safety Population

Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in aspartate aminotransferase (AST)

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
AST - Shift Normal to Normal	28 Participants	28 Participants	24 Participants	—
AST - Shift Normal to Abnormal	1 Participants	4 Participants	5 Participants	—
AST - Shift Abnormal to Normal	3 Participants	1 Participants	4 Participants	—
AST - Shift Abnormal to Abnormal	4 Participants	4 Participants	3 Participants	—
AST - Shift Missing	3 Participants	4 Participants	4 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3

Population: Safety Population

Safety endpoint: Baseline normal/abnormal to Day 3 normal/abnormal in total bilirubin

Outcome measures

Outcome measures
Measure	Istaroxime 0.5 µg/kg/Min n=39 Participants Istaroxime participants receiving 0.5 µg/kg/min (Cohort I)	Placebo Cohort I n=41 Participants Placebo participants enrolled in Cohort I	Istaroxime 1.0 µg/kg/Min n=40 Participants Istaroxime participants receiving 1.0 µg/kg/min (Cohort II)	Placebo Cohort II Placebo participants enrolled in Cohort II
Total Bilirubin - Shift Normal to Abnormal	3 Participants	2 Participants	2 Participants	—
Total Bilirubin - Shift Abnormal to Normal	9 Participants	3 Participants	6 Participants	—
Total Bilirubin - Shift Normal to Normal	9 Participants	21 Participants	13 Participants	—
Total Bilirubin - Shift Abnormal to Abnormal	13 Participants	11 Participants	15 Participants	—
Total Bilirubin - Shift Missing	5 Participants	4 Participants	4 Participants	—

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 23 other events

Deaths: 0 deaths

Istaroxime 0.5 µg/kg/Min

Serious events: 2 serious events

Other events: 31 other events

Deaths: 0 deaths

Istaroxime 1.0 µg/kg/Min

Serious events: 6 serious events

Other events: 33 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=39 participants at risk IV infusion for 24 hours Placebo: IV of matching saline solution	Istaroxime 0.5 µg/kg/Min n=41 participants at risk Istaroxime via IV infusion for 24 hours Istaroxime: IV infusion of istaroxime 0.5 µg/kg/min	Istaroxime 1.0 µg/kg/Min n=40 participants at risk Istaroxime via IV infusion for 24 hours Istaroxime: IV infusion of istaroxime 1.0 µg/kg/min
Cardiac disorders Cardiac failure	2.6% 1/39 • Number of events 1 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	4.9% 2/41 • Number of events 2 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	5.0% 2/40 • Number of events 2 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.
Cardiac disorders Cardiac failure congestive	0.00% 0/39 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	0.00% 0/41 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	2.5% 1/40 • Number of events 1 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.
Cardiac disorders Cardiogenic shock	0.00% 0/39 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	0.00% 0/41 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	2.5% 1/40 • Number of events 1 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.
General disorders Cardiac death	0.00% 0/39 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	0.00% 0/41 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	2.5% 1/40 • Number of events 1 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.
Nervous system disorders Transient ischaemic attack	2.6% 1/39 • Number of events 1 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	0.00% 0/41 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	0.00% 0/40 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.
Renal and urinary disorders Renal embolism	0.00% 0/39 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	0.00% 0/41 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	2.5% 1/40 • Number of events 1 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.
Respiratory, thoracic and mediastinal disorders Hyperventilation	2.6% 1/39 • Number of events 1 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	0.00% 0/41 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	0.00% 0/40 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.
Vascular disorders Hypotension	2.6% 1/39 • Number of events 1 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	0.00% 0/41 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.	0.00% 0/40 • Enrollment to 30 days after enrollment Participants were closely supervised in a hospital. Adverse events were observed by study staff and reported by participants.

Other adverse events

Additional Information

Phillip D. Simmons, Executive Director of Biostatistics & Data Management

Windtree Therapeutics, Inc.

Phone: 215-488-9300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee All data and results of the clinical study are possessed by sponsor and investigator. Investigator agrees not to submit the results of this study for publication or presentation before the sponsor review the accuracy and no leakage of confidential information in the manuscript.
Publication restrictions are in place

Restriction type: OTHER