A Multicenter, Randomized, Placebo-Controlled, Parallel Group Trial on the Safety and Efficacy of Istaroxime for Cardiogenic Shock SCAI Stage C (SEISMiC-C)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Windtree Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

5 Jan 2025 → 31 Jul 2025

Decision date (initial)

2025-05-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Windtree Therapeutics, Inc.

External identifiers

EU CT number

2023-507243-11-02

ClinicalTrials.gov

NCT05975021

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective of this trial is to assess the ability of istaroxime to increase SBP in patients with Society for Cardiovascular Angiography and Interventions (SCAI) Stage C cardiogenic shock, defined as hospitalization for acute decompensated heart failure (ADHF) with persistent hypotension, and since admission to the hospital and throughout screening, have not received digoxin and are not on cardiovascular, respiratory, or renal mechanical support.

Secondary objectives 1

1. To assess other measures of efficacy to ensure consistency of results across multiple endpoints and to examine the utility of endpoints for future studies.

Conditions and MedDRA coding

Cardiogenic Shock

Study design 4 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Signed informed consent form (ICF)
2. Clinical presentation consistent with SCAI Stage C cardiogenic shock caused by ADHF and meeting the criteria in Table 5 1.
3. Admitted to ICU within 36 hours prior to randomization with pulmonary congestion on chest x-ray (airspace opacification, Kerley B lines, pleural effusion, etc.) or lung ultrasound (B-lines) and BNP ≥ 400 pg/mL or NT-proBNP ≥ 1400 pg/mL
4. Males and females, 18 to 85 years of age (inclusive).
5. History of left ventricular ejection fraction (LVEF) ≤ 40%.
6. Persistent hypotension defined as SBP between 70 and 90 mmHg for 2 readings with concomitant signs of hypoperfusion.
7. Echocardiogram during initial hospitalization confirming ejection fraction ≤ 40% and no evidence of other pathology to confound interpretation of cardiac physiology (eg, pericardial effusion).

Exclusion criteria 29

1. 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).
2. 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.
3. Cardiogenic shock due to any other condition besides acute decompensation of chronic heart failure.
4. Any of the following in the past 30 days: acute coronary syndrome, coronary revascularization, MI, CABG, or percutaneous coronary intervention.
5. 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.
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 < 0.5 ng/ml, the patient may be enrolled).
8. Severe renal impairment (eGFR < 30 ml/min, calculated by the MDRD formula).
9. Hypersensitivity to the trial medication and its excipients (including known lactose hypersensitivity) or any related medication.
10. Stroke or TIA within 3 months.
11. Severe obstructive valvular lesions including severe aortic or mitral stenosis.
12. Primary hypertrophic or restrictive cardiomyopathy or systemic illness known to be associated with infiltrative heart disease.
13. 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.
14. Pericardial constriction or active pericarditis.
15. 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.
16. Cardiac resynchronization therapy (CRT), ICD, or pacemaker implantation within the past month.
17. Uncontrolled arrythmia.
18. Sustained hypotension (SBP < 70 mmHg) for at least 30 minutes from the time of arrival to the hospital.
19. Systolic BP > 120 mmHg during the hour prior to randomization.
20. 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° or active infection requiring IV antimicrobial treatment.
23. Body weight < 40 kg or ≥ 150 kg.
24. Laboratory exclusions: a. Hemoglobin < 9 g/dl, b. Platelet count < 100,000/µl, c. 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. Severe pulmonary or thyroid disease.
27. Pregnant, planning on becoming pregnant, or currently breast-feeding.
28. Ongoing drug or alcohol abuse.
29. Participation in another interventional trial within the past 30 days.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Systolic blood pressure (SBP) area under the curve (AUC) from start of infusion to 6 hours.

Secondary endpoints 3

1. Vasoactive-Inotropic Score (VIS) at 24 and 48 hours post baseline. VIS is calculated as doses of dopamine + dobutamine + 100×epinephrine + 50×levosimendan + 10×milrinone + 100×vasopressin + 100×norepinephrine (µg/kg/min), using the dosing rates of vasoactive and inotropic medications.
2. Days alive and out of the hospital through Day 30 from randomization.
3. Time to treatment failure defined by need for initiation of new inotropes or increase in dose of inotropes or mechanical support (circulatory, respiratory, or renal) or death through Day 5 from randomization.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Windtree Therapeutics Inc.

Sponsor organisation

Windtree Therapeutics Inc.

Address

2600 Kelly Road Suite 100

City

Warrington

Postcode

18976-3652

Country

United States

Scientific contact point

Organisation

Windtree Therapeutics Inc.

Contact name

Steven G Simonson

Public contact point

Organisation

Windtree Therapeutics Inc.

Contact name

Phillip D Simmons

Locations

3 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications