The Safety and Efficacy of Istaroxime for Pre-Cardiogenic Shock

NCT ID: NCT04325035

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-28
• Study Completion Date: 2024-10-30

Brief Summary

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.

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.

Conditions

Cardiogenic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

Istaroxime

Intervention Type: DRUG

Reconstituted istaroxime and lactose lyophilized powder delivered via IV infusion

Placebo - Part A

Placebo (lactose lyophilized powder) IV infusion for 24 hours

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Reconstituted placebo (lactose lyophilized powder) delivered via IV infusion

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.

Group Type: EXPERIMENTAL

Istaroxime

Intervention Type: DRUG

Reconstituted istaroxime and lactose lyophilized powder delivered via IV infusion

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.

Group Type: EXPERIMENTAL

Istaroxime

Intervention Type: DRUG

Reconstituted istaroxime and lactose lyophilized powder delivered via IV infusion

Placebo

Intervention Type: DRUG

Reconstituted placebo (lactose lyophilized powder) delivered via IV infusion

Placebo - Part B

Placebo (lactose lyophilized powder) IV infusion for 60 hours.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Reconstituted placebo (lactose lyophilized powder) delivered via IV infusion

Interventions

Istaroxime

Reconstituted istaroxime and lactose lyophilized powder delivered via IV infusion

Intervention Type: DRUG

Placebo

Reconstituted placebo (lactose lyophilized powder) delivered via IV infusion

Intervention Type: DRUG

Other Intervention Names

PST2744; Lactose lyophilized powder

Eligibility 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 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Momentum Research, Inc.

INDUSTRY

Sponsor Role: collaborator

Windtree Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marco Metra, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Italy

Locations

Tufts Medical Center

Boston, Massachusetts, United States

Hospital Italiano de Bueno Aires

Capital Federal, Buenos Aires, Argentina

Santorio Guemes

Capital Federal, Buenos Aires, Argentina

Hospital Privado de Rosario

Rosario, Sante Fe, Argentina

Instituto Cardiovascular de Rosario

Rosario, Sante Fe, Argentina

Santorio de la Trinidad Palermo

Buenos Aires, , Argentina

Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo

Alessandria, , Italy

UOC Cardiologia, ASST degli Spedali Civili di Brescia Pizzale Spedali Civili 1

Brescia, , Italy

IRCCS San Raffaele Scientific Institute

Milan, , Italy

Uniwersytecki Szpital Kliniczny, Centrum Chorub Serca

Wroclaw, Lower Silesian Voivodeship, Poland

Uniwersytecki Szpital Kliniczny w Białymstoku

Bialystok, , Poland

Uniwersytecki Szpital Kliniczny w Opolu

Opole, , Poland

4 Wojskowy Szpital Kliniczny

Wroclaw, , Poland

Countries

United States; Argentina; Italy; Poland

References

Metra M, Chioncel O, Cotter G, Davison B, Filippatos G, Mebazaa A, Novosadova M, Ponikowski P, Simmons P, Soffer J, Simonson S. Safety and efficacy of istaroxime in patients with acute heart failure-related pre-cardiogenic shock - a multicentre, randomized, double-blind, placebo-controlled, parallel group study (SEISMiC). Eur J Heart Fail. 2022 Oct;24(10):1967-1977. doi: 10.1002/ejhf.2629. Epub 2022 Aug 22.

Reference Type: RESULT

PMID: 35867804 (View on PubMed)

Metra M, Chioncel O, Davison B, Filippatos G, Mebazaa A, Pagnesi M, Adamo M, Novosadova M, Ponikowski P, Simmons P, Soffer J, Simonson S, Cotter G. Safety and Efficacy of Istaroxime 1.0 and 1.5 microg/kg/min for Patients With Pre-Cardiogenic Shock. J Card Fail. 2023 Jul;29(7):1097-1103. doi: 10.1016/j.cardfail.2023.03.020. Epub 2023 Apr 17.

Reference Type: RESULT

PMID: 37075941 (View on PubMed)

Other Identifiers

2020-000885-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

04-CL-1904

Identifier Type: -

Identifier Source: org_study_id