An international study at multiple sites testing the safety and effectiveness of an investigational drug called istaroxime, given through a vein in adults 18 – 85 years of age with severe heart failure who also have low blood pressure.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study on the Safety and Efficacy of Istaroxime for Pre-Cardiogenic Shock (SEISMiC). - SEISMiC

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2020-000885-40-IT

Enrollment

Registered

2020-06-23

Start date

2021-04-16

Completion date

Unknown

Last updated

2025-01-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pre-Cardiogenic Shock MedDRA version: 20.0 Level: LLT Classification code 10000803 Term: Acute heart failure System Organ Class: 100000004849

Interventions

Product Name: Istaroxime Product Code: PST2744 Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: Istaroxime CAS Number: 374559-48-5 Other descriptive name: Androstane-3,6,17

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Clinical presentation consistent with SCAI Stage B pre-cardiogenic shock caused by acute decompensation of chronic systolic heart failure (due to arterial hypertension, ischemic heart disease or dilated cardiomyopathy), without evidence for an acute coronary syndrome. 2. Signed informed consent form (ICF); 3. Males and females, 18 to 85 years of age (inclusive); 4. An admission within 36 hours prior to randomization for ADHF episode, defined as: a. Dyspnea, at rest or with minimal exertion, b. Congestion on chest x-ray or lung US with BNP = 400 pg/mL or NT-proBNP = 1400 pg/mL. Elective admissions for medications tune up or procedures do not qualify as an ADHF admission. 5. History of left ventricular ejection fraction (LVEF) = 40%; 6. Persistent hypotension defined as a. SBP between 75 and 90 mmHg for at least 2 hours prior to Screening; b. SBP doesn’t decrease by > 7 mmHg on two separate measurements during the last 2 hours prior to randomization; 7. Heart rate 75 to 150 bpm. If the subject is on a beta-blocker, the range is 60 to 150 bpm; 8. Echocardiogram during index hospitalization confirming ejection fraction = 40% and no evidence of other pathology to confound interpretation of cardiac physiology (eg, pericardial effusion). 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 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30

Exclusion criteria

Exclusion criteria: 1. Cardiogenic shock of SCAI stage C or worse 2. Cardiogenic shock due to any other condition besides acute decompensation of chronic heart failure. 3. Any of the following in the past 30 days: acute coronary syndrome, coronary revascularization, MI, CABG, or percutaneous coronary intervention; 4. Current treatment (within 6 hours of Screening) with positive inotropic agents or vasopressors, renal support including ultrafiltration, or mechanical circulatory, ventilatory or renal support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device); 5. Venous Lactate > 2 mmol/L; 6. History of heart transplant or UNOS priority 1a heart transplant listing 7. Ongoing treatment with digoxin (if digoxin was stopped before signing the ICF and the digoxin plasma level is 38° or active infection requiring IV antimicrobial treatment; 22. Body weight 5.3 mmol/l or < 3.5 mmol/l; 24. A life expectancy < 3 months in the opinion of the investigator; 25. Severe pulmonary or thyroid disease; 26. Pregnant or breast-feeding; 27. Ongoing drug or alcohol abuse; 28. Participation in another interventional study within the past 30 days.

Design outcomes

Primary

Measure	Time frame
Main Objective: The primary objective of this study is to assess the ability of istaroxime to increase SBP in patients with cardiogenic shock or pre-shock, defined as hospitalization for acute decompensated heart failure (ADHF) with persistent hypotension (SBP 75-90 mmHg for two hours) who, for at least 6 hours prior to Screening, who are not on cardiovascular, respiratory, or renal mechanical support, and have not received IV vasopressors or inotropes.;Secondary Objective: To assess other measures of efficacy to ensure consistency of results across multiple endpoints.;Primary end point(s): •SBP area under the curve (AUC) to 6 hours from start of infusion. ;Timepoint(s) of evaluation of this end point: 6 hours from start of infusion.	—

Measure

Time frame

Main Objective: The primary objective of this study is to assess the ability of istaroxime to increase SBP in patients with cardiogenic shock or pre-shock, defined as hospitalization for acute decompensated heart failure (ADHF) with persistent hypotension (SBP 75-90 mmHg for two hours) who, for at least 6 hours prior to Screening, who are not on cardiovascular, respiratory, or renal mechanical support, and have not received IV vasopressors or inotropes.;Secondary Objective: To assess other measures of efficacy to ensure consistency of results across multiple endpoints.;Primary end point(s): •SBP area under the curve (AUC) to 6 hours from start of infusion. ;Timepoint(s) of evaluation of this end point: 6 hours from start of infusion.

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Secondary

Measure	Time frame
Secondary end point(s): • Treatment-failure score, based on death, circulatory, respiratory, or renal mechanical support or intravenous inotrope or vasopressor treatment, and changes in systolic blood pressure • Change from baseline in SBP at 6 and 24 hours of treatment, measured via a sphygmomanometer or arterial line. • SBP area under the curve (AUC) to 24 hours from infusion start. • Number of subjects with increases from baseline in SBP = 5% and = 10 mmHg at a timepoint between 4-6 hours after dosing and at least one other measurement separated by = 2 hours during the 24 hours infusion. • Number of subjects requiring treatment with intravenous vasopressors, inotropes, and/or mechanical cardiac or renal support or have died from randomization to 24 hours and Day 5 (“treatment failure”). • Changes in quality of life measured by the EQ-5D from baseline to Day 5 (96 hours) from infusion start and at Day 30. • Change from baseline in Creatinine clearance at 24, 48, 72 and 96 hours from infusion start. • Change from baseline and observed heart rate measurements at 12, 24, 48, 72 and 96 hours from infusion start. • Change from baseline and observed mean arterial pressure (MAP) at 12, 24, 48, 72 and 96 hours from infusion start. • Change from baseline and observed brain natriuretic peptide (BNP), NT-pro-BNP, troponin (cTn; either T or I) and venous lactate at 12, 24, 48, 72 and 96 hours from infusion start. • Time to worsening heart failure through Day 5. • Time to HF re-admission or death through Day 30. • Length in ICU/length of initial hospitalization • Days alive and out of acute care (including all intensive acute care units). • Days alive and out of the hospital through Day 30 • Number of subjects with hospital re-admissions through Day 30 • Mortality and reasons for death through Day 30 • For patients who are invasively monitored with a pulmonary artery catheter – changes in invasive hemodynamic parameters from pre-treatment to 3, 6, 12, 24 and 30 hours • C	—

Measure

Time frame

Secondary end point(s): • Treatment-failure score, based on death, circulatory, respiratory, or renal mechanical support or intravenous inotrope or vasopressor treatment, and changes in systolic blood pressure • Change from baseline in SBP at 6 and 24 hours of treatment, measured via a sphygmomanometer or arterial line. • SBP area under the curve (AUC) to 24 hours from infusion start. • Number of subjects with increases from baseline in SBP = 5% and = 10 mmHg at a timepoint between 4-6 hours after dosing and at least one other measurement separated by = 2 hours during the 24 hours infusion. • Number of subjects requiring treatment with intravenous vasopressors, inotropes, and/or mechanical cardiac or renal support or have died from randomization to 24 hours and Day 5 (“treatment failure”). • Changes in quality of life measured by the EQ-5D from baseline to Day 5 (96 hours) from infusion start and at Day 30. • Change from baseline in Creatinine clearance at 24, 48, 72 and 96 hours from infusion start. • Change from baseline and observed heart rate measurements at 12, 24, 48, 72 and 96 hours from infusion start. • Change from baseline and observed mean arterial pressure (MAP) at 12, 24, 48, 72 and 96 hours from infusion start. • Change from baseline and observed brain natriuretic peptide (BNP), NT-pro-BNP, troponin (cTn; either T or I) and venous lactate at 12, 24, 48, 72 and 96 hours from infusion start. • Time to worsening heart failure through Day 5. • Time to HF re-admission or death through Day 30. • Length in ICU/length of initial hospitalization • Days alive and out of acute care (including all intensive acute care units). • Days alive and out of the hospital through Day 30 • Number of subjects with hospital re-admissions through Day 30 • Mortality and reasons for death through Day 30 • For patients who are invasively monitored with a pulmonary artery catheter – changes in invasive hemodynamic parameters from pre-treatment to 3, 6, 12, 24 and 30 hours • C

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Countries

China, France, Italy, Poland, Romania, Russian Federation, United States

Contacts

Public ContactClinical Operation

Clinical Consulting Sp. z o.o.

tadeusz.baron@clinicalconsulting.pl+48322272005

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026