Testing istaroxime for treating severe heart failure

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

This study is testing if a new heart medication called istaroxime can help people with severe heart failure and low blood pressure feel better and improve their heart function.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: Windtree Therapeutics (Industry-sponsored)
• Locations: 2 sites (Portland, Oregon and 1 other locations)
• Trial ID: NCT05975021 on ClinicalTrials.gov

What this trial studies

This trial evaluates the safety and efficacy of istaroxime in patients experiencing SCAI Stage C cardiogenic shock, a critical condition characterized by low blood pressure and reduced oxygen delivery to organs. Participants will receive standard care for heart failure, with half randomly assigned to receive istaroxime, which may enhance blood pressure and cardiac function. The study aims to determine if istaroxime can provide a better alternative to existing therapies for acute heart failure and cardiogenic shock.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 85 with SCAI Stage C cardiogenic shock and a history of reduced left ventricular ejection fraction.

Not a fit: Patients with other confounding cardiac conditions or those not meeting the specific inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients suffering from severe heart failure and cardiogenic shock.

How similar studies have performed: While istaroxime has been studied previously, this specific application in cardiogenic shock represents a novel approach.

Eligibility criteria

Inclusion Criteria:

* 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;
* 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)

Exclusion Criteria:

* 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
* 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:

  1. Hemoglobin \< 9 g/dl,
  2. Platelet count \< 100,000/µl,
  3. 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.

Where this trial is running

Portland, Oregon and 1 other locations

• Oregon Health and Sciences University — Portland, Oregon, United States (Not_yet_recruiting)
• Kaplan Medical Center — Reẖovot, Israel (Recruiting)

Study contacts

• Study coordinator: Phillip D Simmons, MS

Conditions Cardiogenic Shock