The Safety and Efficacy of Istaroxime for Pre-Cardiogenic Shock (SEISMiC)

January 30, 2025 updated by: Windtree Therapeutics

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

This is a pilot, multinational, randomized, double-blind, placebo-controlled, 2-part safety and efficacy study. Subjects will consist of patients hospitalized for acute decompensated heart failure with persistent hypotension.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a pilot, multinational, multicenter, randomized, double-blind, placebo-controlled, 2-part safety and efficacy study. Subjects will consist of males or females 18 to 85 years of age, hospitalized for acute decompensated heart failure (ADHF) with persistent hypotension (systolic blood pressure [SBP] 70-100 mmHg for two hours).

Part A will dose all subjects for 24 hours with either 1.0 µg/kg/min or placebo; Part B will dose all subjects for 60 hours with two different regimens of istaroxime or placebo. Enrollment of Part A and Part B will be sequential.

Up to 30 sites in Part A; up to 15 sites in Part B. Sites may be located in Europe, Asia, South America, and North America.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1425
        • Santorio de la Trinidad Palermo
    • Buenos Aires
      • Capital Federal, Buenos Aires, Argentina, C1199
        • Hospital Italiano de Bueno Aires
      • Capital Federal, Buenos Aires, Argentina, CP1180
        • Santorio Guemes
    • Sante Fe
      • Rosario, Sante Fe, Argentina, S20000GAP
        • Hospital Privado de Rosario
      • Rosario, Sante Fe, Argentina, S2000DSR
        • Instituto Cardiovascular de Rosario
  • Italy
      • Alessandria, Italy
        • Azienda ospedaliera Santi Antonio e Biagio e Cesare Arrigo
      • Brescia, Italy, 25123
        • UOC Cardiologia, ASST degli Spedali Civili di Brescia Pizzale Spedali Civili 1
      • Milan, Italy, 20132
        • IRCCS San Raffaele Scientific Institute
  • Poland
      • Białystok, Poland, 15-276
        • Uniwersytecki Szpital Kliniczny w Białymstoku
      • Opole, Poland, 45-401
        • Uniwersytecki Szpital Kliniczny w Opolu
      • Wroclaw, Poland, 50-981
        • 4 Wojskowy Szpital Kliniczny
    • Dolnoslaskie
      • Wrocław, Dolnoslaskie, Poland, 50-556
        • Uniwersytecki Szpital Kliniczny, Centrum Chorub Serca
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 for acute decompensated heart failure (ADHF) episode within 36 hours prior to randomization, defined as:

    1. Dyspnea, at rest or with minimal exertion;
    2. Congestion on chest x-ray or lung US with B-type natriuretic peptide (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:

    1. SBP of 75 to 90 mmHg (Part A) or 70 to 100 mmHg (Part B) for ≥ 2 hours prior to Screening;
    2. SBP does not 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 initial hospitalization confirming ejection fraction ≤ 40% and no evidence of other pathology to confound interpretation of cardiac physiology (e.g., pericardial effusion);
  9. Subject is monitored by a Pulmonary Artery Catheter (PAC) at the time of randomization (Part B only).

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, myocardial infarction (MI), coronary artery bypass graft (CABG), or percutaneous coronary intervention;
  4. Current (within 6 hours of Screening) or anticipated need for treatment 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 United Network for Organ Sharing (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 < 0.5 ng/ml, the patient may be enrolled);
  8. Severe renal impairment (estimated glomerular filtration rate (eGFR) < 30 ml/min, calculated by the Modification of Diet in Renal Disease (MDRD) formula);
  9. Hypersensitivity to the study medication or any of its excipients (including known lactose hypersensitivity) or any related medication;
  10. Stroke or transient ischemic attack (TIA) within 3 months;
  11. Active coronary ischemia;
  12. Any significant valvular disease (including any moderate or severe valvular stenosis, moderate or severe aortic or pulmonary regurgitation, stenosis or regurgitation);severe tricuspid or mitral regurgitation);
  13. Primary hypertrophic or restrictive cardiomyopathy or systemic illness known to be associated with infiltrative heart disease;
  14. Admission for AHF triggered primarily by a correctable etiology such as significant arrhythmia, (inclusive of atrial fibrillation as the main reason for admission), infection, severe anemia, acute coronary syndrome, pulmonary embolism, exacerbation of chronic obstructive pulmonary disease (COPD), planned admission for device implantation, or over-diuresis as a cause of hypotension;
  15. Pericardial constriction or active pericarditis;
  16. Life-threatening ventricular arrhythmia or implantable cardioverter defibrillator (ICD) shock within the past month or history of sudden death within 6 months;
  17. Cardiac resynchronization therapy (CRT), ICD, or pacemaker implantation (or planned implantation) within the past 3 months;
  18. Sustained ventricular tachycardia in the last 3 months with no defibrillator;
  19. Sustained hypotension (SBP < 70 mmHg) for at least 30 minutes from the time of arrival to the hospital;
  20. Severe pulmonary disease or cor pulmonale or other causes of isolated right-sided HF or not related to left ventricular dysfunction;
  21. Acute respiratory distress syndrome;
  22. Suspected sepsis; fever > 38°C or active infection requiring IV antimicrobial treatment;
  23. Body weight < 40 kg or ≥ 150 kg;

  24. Laboratory exclusions:

    1. Hemoglobin < 9 g/dl,
    2. Platelet count < 100,000/µl,
    3. Serum potassium > 5.3 mmol/l or < 3.5 mmol/l;
  25. A life expectancy < 3 months based on the judgment of the investigator;
  26. Uncontrolled thyroid disease;
  27. Pregnant or breast-feeding;
  28. Ongoing drug or alcohol abuse;
  29. Participation in another interventional study within the past 30 days.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Istaroxime - Part A
Istaroxime IV infusion for 24 hours. Istaroxime administration can begin at 1.0 or 1.5 µg/kg/min; the target infusion rate is 1.5 µg/kg/min
Drug: Istaroxime
Reconstituted istaroxime and lactose lyophilized powder delivered via IV infusion
Other Names:
  • PST2744
Placebo Comparator: Placebo - Part A
Placebo (lactose lyophilized powder) IV infusion for 24 hours
Drug: Placebo
Reconstituted placebo (lactose lyophilized powder) delivered via IV infusion
Other Names:
  • Lactose lyophilized powder
Experimental: Istaroxime - Part B
Istaroxime IV infusion at 1.0 µg/kg/min for 6 hours, 0.5 µg/kg/min for 42 hours, 0.25 µg/kg/min for 12 hours.
Drug: Istaroxime
Reconstituted istaroxime and lactose lyophilized powder delivered via IV infusion
Other Names:
  • PST2744
Experimental: Istaroxime and Placebo - Part B
Istaroxime IV infusion at 0.5 µg/kg/min for 48 hours, followed by placebo IV infusion for 12 hours.
Drug: Istaroxime
Reconstituted istaroxime and lactose lyophilized powder delivered via IV infusion
Other Names:
  • PST2744
Drug: Placebo
Reconstituted placebo (lactose lyophilized powder) delivered via IV infusion
Other Names:
  • Lactose lyophilized powder
Placebo Comparator: Placebo - Part B
Placebo (lactose lyophilized powder) IV infusion for 60 hours.
Drug: Placebo
Reconstituted placebo (lactose lyophilized powder) delivered via IV infusion
Other Names:
  • Lactose lyophilized powder

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change from baseline in systolic blood pressure (SBP) area under the curve (AUC) 0-6
Time Frame: 0 to 6 hours after initiation of infusion
Change from baseline AUC for systolic blood pressure
0 to 6 hours after initiation of infusion

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from baseline in SBP AUC 0-48
Time Frame: 0 to 60 hours after initiation of infusion
Change from baseline in AUC for systolic blood pressure in Part B
0 to 60 hours after initiation of infusion
Change from baseline in SBP AUC 0-60
Time Frame: 0 to 48 hours after initiation of infusion
Change from baseline in AUC for systolic blood pressure in Part B
0 to 48 hours after initiation of infusion
Treatment failure score
Time Frame: 60 hours from initiation of infusion
Treatment-failure score, based on death, circulatory, respiratory, or renal mechanical support or intravenous inotrope or vasopressor treatment, and changes in systolic blood pressure
60 hours from initiation of infusion
Change from baseline in SBP
Time Frame: 6 hours after initiation of infusion
Change from baseline in systolic blood pressure
6 hours after initiation of infusion
Change from baseline in SBP
Time Frame: 24 hours after initiation of infusion
Change from baseline in systolic blood pressure
24 hours after initiation of infusion
Change from baseline in SBP
Time Frame: 48 hours after initiation of infusion
Change from baseline in systolic blood pressure in Part B
48 hours after initiation of infusion
Change from baseline in SBP
Time Frame: 60 hours after initiation of infusion
Change from baseline in systolic blood pressure in Part B
60 hours after initiation of infusion
Number of treatment failures
Time Frame: Randomization to 24 hours for Part A
Number of subjects requiring treatment with intravenous vasopressors, inotropes, and/or mechanical cardiac or renal support or have died
Randomization to 24 hours for Part A
Number of treatment failures
Time Frame: Randomization to 48 hours for Part B
Number of subjects requiring treatment with intravenous vasopressors, inotropes, and/or mechanical cardiac or renal support or have died
Randomization to 48 hours for Part B
Number of treatment failures
Time Frame: Randomization to Day 5
Number of subjects requiring treatment with intravenous vasopressors, inotropes, and/or mechanical cardiac or renal support or have died
Randomization to Day 5
Change in quality of life
Time Frame: Baseline to Day 5 (96 hours) from infusion start
Changes from baseline measured by the EQ-5D in Part A
Baseline to Day 5 (96 hours) from infusion start
Change in quality of life
Time Frame: Baseline to Day 30 from infusion start
Changes from baseline measured by the EQ-5D in Part A
Baseline to Day 30 from infusion start
Change in eGFR
Time Frame: 24 hours from infusion start
Change from baseline and observed estimated glomerular filtration rate (eGFR)
24 hours from infusion start
Change in eGFR
Time Frame: 48 hours from infusion start
Change from baseline and observed estimated glomerular filtration rate (eGFR)
48 hours from infusion start
Change in brain natriuretic peptide (BNP), N-terminal pro hormone B-type natriuretic peptide (NT-pro-BNP), troponin (cTn; either T or I) and venous lactate
Time Frame: 24 hours from infusion start
Change from baseline and observed BNP, NT-pro-BNP, troponin (cTn; either T or I) and venous lactate
24 hours from infusion start
Change in brain natriuretic peptide (BNP), N-terminal pro hormone B-type natriuretic peptide (NT-pro-BNP), troponin (cTn; either T or I) and venous lactate
Time Frame: 48 hours from infusion start
Change from baseline and observed BNP, NT-pro-BNP, troponin (cTn; either T or I) and venous lactate
48 hours from infusion start
Time to worsening heart failure (HF)
Time Frame: Up to Day 5
Time to worsening HF
Up to Day 5
Time to HF re-admission or death
Time Frame: Up to Day 30
Time to HF re-admission or death
Up to Day 30
Length of initial hospitalization
Time Frame: Up to Day 30
Length of initial hospitalization
Up to Day 30
Days alive and out of the hospital
Time Frame: Up to Day 30
Days alive and out of the hospital
Up to Day 30
Mortality and reasons for death
Time Frame: Up to Day 30
Mortality and reasons for death
Up to Day 30
Change in coronary index (CI)
Time Frame: 24 hours
Change from baseline in CI as assessed by echocardiogram - Part A
24 hours
Change in E to e' ratio
Time Frame: 24 hours
Change from baseline in E to e' ratio as assessed by echocardiogram - Part A
24 hours
Change in stroke volume index (SVI)
Time Frame: 24 hours
Change from baseline in SVI as assessed by echocardiogram - Part A
24 hours
Change in left atrium area (LAA)
Time Frame: 24 hours
Change from baseline in LAA as assessed by echocardiogram - Part A
24 hours
Change in CI
Time Frame: 48 hours
Change from baseline in CI as assessed by echocardiogram - Part B
48 hours
Change in E to e' ratio
Time Frame: 48 hours
Change from baseline in E to e' ratio as assessed by echocardiogram - Part B
48 hours
Change in SVI
Time Frame: 48 hours
Change from baseline in SVI as assessed by echocardiogram - Part B
48 hours
Change in LAA
Time Frame: 48 hours
Change from baseline in LAA as assessed by echocardiogram - Part B
48 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Windtree Therapeutics

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Momentum Research, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Marco Metra, MD, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 28, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 26, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 24, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 26, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 27, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 30, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 04-CL-1904
  • 2020-000885-40 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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