Cardiogenic ShockPhase 1/2SEISMiC-CNCT05975021
A Safety and Efficacy Trial of Istaroxime for Cardiogenic Shock Stage C
A Phase 1/2 study testing Istaroxime in people with Cardiogenic Shock, run by Windtree Therapeutics at 15 sites in 5 countries.
Trial summary
The current trial aims to assess the effect of istaroxime in patients with SCAI Stage C Cardiogenic Shock (CS). These patients look unwell, frequently with a sudden change in mental status, mottled and cool extremities, and delayed capillary refill, as well as signs of congestion and relative low blood pressure and… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Cardiogenic Shock
- What is being tested?
- Istaroxime
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 15 sitesin 5 countries
- Study dates
- 1 Jun 2024to 31 Aug 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent form (ICF);
- Clinical presentation consistent with SCAI Stage C cardiogenic shock caused by ADHF and meeting the criteria in below table;
- Admitted to ICU within 36 hours prior to randomization with congestion on chest x-ray or lung ultrasound and BNP ≥ 400 pg/mL or NT-proBNP ≥ 1400 pg/mL;
- Males and females, 18 to 85 years of age (inclusive);
- History of left ventricular ejection fraction (LVEF) ≤ 40%;
- Persistent hypotension defined as SBP between 70 and 90 mmHg for 2 readings with concomitant signs of hypoperfusion;
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- Echocardiogram during initial hospitalization confirming ejection fraction ≤ 40% and no evidence of other pathology to confound interpretation of cardiac physiology (eg, pericardial effusion).
- Table: Definition of SCAI Stage C Required for Inclusion. These criteria must be present at screening or prior to screening in patients actively treated by vasoactive agents or/and inotropes concomitantly (at the same time)
- Must have at Least One of:
- Hypoperfusion: Venous Lactate ≥ 2 mmol/L, urine output < 30 mL/hour, cold and clammy or acute alteration in mental status.
- Hemodynamic Instability: SBP 70-90 mmHg, cardiac index < 2.2 L/min/meter2 and PCW > 15 mmHg
- Without Any Of:
- Venous lactate > 5 mmol/L
- Worsening clinical status despite initial therapy (e.g., worsening hemodynamics, worsening renal or liver function)
- ALT >500 U/L (8.333 µkat/L)
Who cannot join
- Patient is in SCAI B (BP increased above 90 mmHg despite no vasoactive or inotrope therapy) or SCAI D (continuously deteriorating BP and hypoperfusion despite vasoactive or inotrope therapy);
- Lactate < 2 mmol/L (unless the patient meets the criteria in bullet 2 of Table 5-1) or lactate > 5 mmol/L prior to randomization;
- Cardiogenic shock due to any other condition besides acute decompensation of chronic heart failure;
- Any of the following in the past 30 days: acute coronary syndrome, coronary revascularization, MI, CABG, or percutaneous coronary intervention;
- Current (within 6 hours of screening) or anticipated need for treatment with renal support including ultrafiltration, or mechanical circulatory, ventilatory or renal support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device) such as persistent hypoperfusion and hypotension;
- History of heart transplant or UNOS priority 1a heart transplant listing
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- 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);
- Severe renal impairment (eGFR < 30 ml/min, calculated by the MDRD formula);
- Hypersensitivity to the trial medication and its excipients (including known lactose hypersensitivity) or any related medication;
- Stroke or TIA within 3 months;
- Severe obstructive valvular lesions including severe aortic or mitral stenosis;
- Primary hypertrophic or restrictive cardiomyopathy or systemic illness known to be associated with infiltrative heart disease;
- 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 COPD, planned admission for device implantation, or over-diuresis as a cause of hypotension;
- Pericardial constriction or active pericarditis;
- Significant ventricular arrhythmia prior to screening (such as sustained ventricular tachycardia or ventricular fibrillation) or implantable cardioverter defibrillator (ICD) shock within the past month or history of sudden death within 6 months;
- Cardiac resynchronization therapy (CRT), ICD, or pacemaker implantation within the past month;
- Uncontrolled arrythmia;
- Sustained hypotension (SBP < 70 mmHg) for at least 30 minutes from the time of arrival to the hospital;
- Systolic BP > 120 mmHg during the hour prior to randomization
- Cor pulmonale or other causes of isolated right-sided HF or not related to left ventricular dysfunction;
- Acute respiratory distress syndrome;
- Suspected sepsis; fever > 38° or active infection requiring IV antimicrobial treatment;
- Body weight < 40 kg or ≥ 150 kg;
- Laboratory exclusions:
- Hemoglobin < 9 g/dl,
- Platelet count < 100,000/µl,
- Serum potassium > 5.3 mmol/l or < 3.5 mmol/l;
- A life expectancy < 3 months based on the judgment of the investigator;
- Severe pulmonary or thyroid disease;
- Pregnant, planning on becoming pregnant, or currently breast-feeding;
- Ongoing drug or alcohol abuse;
- Participation in another interventional trial within the past 30 days.
Trial locations and contacts
15 sites in 5 countries.
15 sites in 5 countries
Argentina4 sites
Sanatorio Güemes
Capital Federal, Buenos Aires, 1180
Sanatorio De la Trinidad Palermo
Capital Federal, Buenos Aires, 1425
Instituto Cardiovascular de Rosario
Rosario, Sante Fe, S2000DSR
Hospital Privado de Rosario
Rosario, Sante Fe, S2000GAP
Italy4 sites
Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo
Alessandria, 15121
ASST degli Spedali Civili di Brescia
Brescia, 25123
IRCCS San Raffaele Scientific Institute
Milan, 20132
University of Turin, Città della Salute e della Scienza
Turin, 10123
Poland4 sites
Uniwersytecki Szpital Kliniczny w Białymstoku
Bialystok, 15-276
Uniwersytecki Szpital Kliniczny w Opolu
Opole, 45-401
Uniwersytecki Szpital Kliniczny, Instytut Chorob Serca
Wroclaw, 50-556
4 Wojskowy Szpital Kliniczny z Polikliniką SP ZOZ
Wroclaw, 50-981
United States2 sites
Tufts Medical Center
Boston, Massachusetts, 02111
Oregon Health and Sciences University
Portland, Oregon, 97201
About this study
Official title: A Multicenter, Randomized, Placebo-Controlled, Parallel Group Trial on the Safety and Efficacy of Istaroxime for Cardiogenic Shock SCAI Stage C
The current trial aims to assess the effect of istaroxime in patients with SCAI Stage C Cardiogenic Shock (CS). These patients look unwell, frequently with a sudden change in mental status, mottled and cool extremities, and delayed capillary refill, as well as signs of congestion and relative low blood pressure and signs of hypoperfusion (reduced oxygen to organs) which frequently require support with rescue therapies including inotropes, vasopressors, or mechanical devices.
Windtree Therapeutics, Inc. has been studying istaroxime, which has the potential to treat patients in this condition without some of the disadvantages of existing therapies being used to treat patients with acute heart failure and CS.
Participants enrolled in this trial will receive standard of care (SoC) therapy for heart failure and CS. Additionally, half of the participants will be randomly chosen to receive istaroxime. Istaroxime has the potential to increase blood pressure and improve cardiac function.
- Conditions
- Cardiogenic Shock
- Being tested
- Istaroxime, Placebo
- Medical subject headings
- Shock, Cardiogenic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IstaroximeDrug
Also called PST2744
IV infusion via a syringe pump. Dosage of 1.0 µg/kg/min for 6 hours; 0.5 µg/kg/min for 42 hours. Total duration 48 hours.
PlaceboDrug
Also called Lactate
IV infusion via a syringe pump. Total duration 48 hours.
| Study group | Role | What they receive |
|---|---|---|
| Istaroxime | Experimental | Istaroxime delivered as an IV infusion via a syringe pump. Dosage regime is 1.0 µg/kg/min for 6 hours, 0.5 µg/kg/min for 42 hours. Total duration 48 hours. Receives: Drug: Istaroxime |
| Placebo | Placebo comparator | Placebo (lactose) delivered as an IV infusion via a syringe pump. Total duration 48 hours. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
SBP AUC 0-6
Systolic blood pressure (SBP) area under the curve (AUC) from start of infusion to 6 hours
Measured: Start of infusion to 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2023
- Study start1 Jun 2024
- Primary completion28 Jul 2025
- Study completion31 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiogenic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a pilot, multinational, multicenter, randomized, double-blind, placebo-controlled, safety and efficacy trial. Participants 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 to 90 mmHg for two readings with concomitant signs of hypoperfusion), and mild to moderate renal impairment.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Windtree Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Steven G Simonson, MD, Study director, Windtree Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05975021
- Sponsor's protocol ID
- 04-CL-2201
- Other IDs
- CT Id: 2023-507243-11-00
- Acronym
- SEISMiC-C
- Status last verified
- Aug 2025
- First submitted
- 26 Jul 2023
- Last updated
- 20 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The preparation and submittal for publication of a manuscript containing the study results shall be in accordance with a process determined by a mutual written agreement between Windtree and participating institutions. The publication or presentation of any study results shall comply with all applicable privacy laws, including but not limited to HIPAA. This trial will be registered in the ClinicalTrials.gov and the CTIS databases, and results information from this trial will be submitted to both. In addition, every attempt will be made to publish results in peer-reviewed journals.
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Placebo-Controlled, Parallel Group Trial on the Safety and Efficacy of Istaroxime for Cardiogenic Shock SCAI Stage C
- ClinicalTrials.gov ID
- NCT05975021
- Acronym / sponsor ID
- SEISMiC-C / 04-CL-2201
- Conditions
- Cardiogenic Shock
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Windtree TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 1 Jun 2024 (actual)
- Primary completion
- 28 Jul 2025 (actual)
- Study completion
- 31 Aug 2026 (estimated)
- First posted
- 3 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The current trial aims to assess the effect of istaroxime in patients with SCAI Stage C Cardiogenic Shock (CS). These patients look unwell, frequently with a sudden change in mental status, mottled and cool extremities, and delayed capillary refill, as well as signs of congestion and relative low blood pressure and signs of hypoperfusion (reduced oxygen to organs) which frequently require support with rescue therapies including inotropes, vasopressors, or mechanical devices.
Windtree Therapeutics, Inc. has been studying istaroxime, which has the potential to treat patients in this condition without some of the disadvantages of existing therapies being used to treat patients with acute heart failure and CS.
Participants enrolled in this trial will receive standard of care (SoC) therapy for heart failure and CS. Additionally, half of the participants will be randomly chosen to receive istaroxime. Istaroxime has the potential to increase blood pressure and improve cardiac function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- This is a pilot, multinational, multicenter, randomized, double-blind, placebo-controlled, safety and efficacy trial. Participants 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 to 90 mmHg for two readings with concomitant signs of hypoperfusion), and mild to moderate renal impairment.
| Arm | Type | Receives |
|---|---|---|
| Istaroxime | Experimental | Drug: IstaroximeIstaroxime delivered as an IV infusion via a syringe pump. Dosage regime is 1.0 µg/kg/min for 6 hours, 0.5 µg/kg/min for 42 hours. Total duration 48 hours. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo (lactose) delivered as an IV infusion via a syringe pump. Total duration 48 hours. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Signed informed consent form (ICF);
- Clinical presentation consistent with SCAI Stage C cardiogenic shock caused by ADHF and meeting the criteria in below table;
- Admitted to ICU within 36 hours prior to randomization with congestion on chest x-ray or lung ultrasound and BNP ≥ 400 pg/mL or NT-proBNP ≥ 1400 pg/mL;
- Males and females, 18 to 85 years of age (inclusive);
- History of left ventricular ejection fraction (LVEF) ≤ 40%;
Key exclusion criteria (32 listed)
- Patient is in SCAI B (BP increased above 90 mmHg despite no vasoactive or inotrope therapy) or SCAI D (continuously deteriorating BP and hypoperfusion despite vasoactive or inotrope therapy);
- Lactate < 2 mmol/L (unless the patient meets the criteria in bullet 2 of Table 5-1) or lactate > 5 mmol/L prior to randomization;
- Cardiogenic shock due to any other condition besides acute decompensation of chronic heart failure;
- Any of the following in the past 30 days: acute coronary syndrome, coronary revascularization, MI, CABG, or percutaneous coronary intervention;
- Current (within 6 hours of screening) or anticipated need for treatment with renal support including ultrafiltration, or mechanical circulatory, ventilatory or renal support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device) such as persistent hypoperfusion and hypotension;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IstaroximeAlso: PST2744IV infusion via a syringe pump. Dosage of 1.0 µg/kg/min for 6 hours; 0.5 µg/kg/min for 42 hours. Total duration 48 hours. | Drug | Istaroxime |
| PlaceboAlso: LactateIV infusion via a syringe pump. Total duration 48 hours. | Drug | Placebo |
Primary outcome
SBP AUC 0-6
Time frame: Start of infusion to 6 hours
Systolic blood pressure (SBP) area under the curve (AUC) from start of infusion to 6 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2025.
- Individual participant dataSharing planned: Yes. The preparation and submittal for publication of a manuscript containing the study results shall be in accordance with a process determined by a mutual written agreement between Windtree and participating institutions. The publication or presentation of any study results shall comply with all applicable privacy laws, including but not limited to HIPAA. This trial will be registered in the ClinicalTrials.gov and the CTIS databases, and results information from this trial will be submitted to both. In addition, every attempt will be made to publish results in peer-reviewed journals.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven G Simonson, MD study director
Windtree Therapeutics, Inc.
15 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Istaroxime in people with Cardiogenic Shock, run by Windtree Therapeutics at 15 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 20 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Argentina, Italy, Poland, United States, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
SBP AUC 0-6 (time frame: Start of infusion to 6 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2025.