The Safety and Efficacy of Istaroxime for Pre-Cardiogenic Shock

• Status: Recruiting
• Trial end date: 2021-09-30
• Target enrollment: 0
• Participant gender: All

Summary

This is a pilot, multinational, randomized, double-blind, placebo-controlled safety and efficacy study. Subjects will consist of patients hospitalized for acute decompensated heart failure with persistent hypotension and heart rate 75 to 150 beats/minute.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Windtree Therapeutics
• Collaborator: Momentum Research, Inc.

Criteria

Inclusion Criteria:

1. Signed informed consent form (ICF);

2. Males and females, 18 to 85 years of age (inclusive);

3. An admission within 36 hours prior to randomization for acute decompensated heart failure (ADHF) episode, 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 N-terminal-pro hormone BNP (NT-proBNP) ≥ 1400 pg/mL;

4. History of left ventricular ejection fraction (LVEF) < 40%;

5. Persistent hypotension defined as:

1. SBP between 75 and 90 mmHg for at least 2 hours prior to Screening;

2. SBP doesn't decrease by > 7 mmHg on two separate measurements during the last 2 hours prior to randomization;

6. Heart rate 75 to 150 bpm. If the subject is on a beta-blocker, the range is 60 to 150 bpm;

7. Echocardiogram confirming ejection fraction < 40% and no evidence of other pathology to confound interpretation of cardiac physiology (eg, pericardial effusion).

Exclusion Criteria:

1. 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);

2. Lactate > 2 mmol/L;

3. History of heart transplant or priority 1a heart transplant listing (United Network for Organ Sharing; UNOS)

4. 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);

5. Severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 ml/min, calculated by the Modification of Diet in Renal Disease [MDRD] formula);

6. Hypersensitivity to the study medication or any related medication;

7. 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;

8. Stroke or transient ischemic attack (TIA) within 3 months;

9. Incomplete revascularization (patients with ischemic heart disease have to have had a catheterization in the last year demonstrating that the main coronary arteries are well revascularized);

10. Moderate or severe valvular disease, such as severe Aortic stenosis or regurgitation; Severe tricuspid or mitral regurgitation;

11. Primary hypertrophic or restrictive cardiomyopathy or systemic illness known to be associated with infiltrative heart disease;

12. Admission for AHF triggered primarily by a correctable etiology such as significant arrhythmia, 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;

13. Pericardial constriction or active pericarditis;

14. Life-threatening ventricular arrhythmia or implantable cardioverter defibrillator (ICD) shock within the past month or history of sudden death within 6 months;

15. Cardiac resynchronization therapy (CRT), ICD, or pacemaker implantation within the past month;

16. Sustained ventricular tachycardia in the last 3 months with no defibrillator;

17. Cor pulmonale or other causes of isolated right-sided HF or not related to left ventricular dysfunction;

18. Acute respiratory distress syndrome;

19. Suspected sepsis; fever > 38° or active infection requiring IV antimicrobial treatment;

20. Body weight < 40 kg or ≥ 130 kg;

21. 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;

22. Cirrhosis or malignancy with a life expectancy < 3 months;

23. Severe pulmonary or thyroid disease;

24. Pregnant or breast-feeding;

25. Ongoing drug or alcohol abuse;

26. Participation in another interventional study within the past 30 days.