Resumen

El presente ensayo tiene como objetivo evaluar el efecto de la istaroxima en pacientes con shock cardiogénico (SC) SCAI estadio C. Estos pacientes presentan mal estado general, frecuentemente con cambio brusco en el estado mental, extremidades moteadas y frías, y relleno capilar enlentecido, así como signos de congestión, presión arterial relativamente baja y signos de hipoperfusión (reducción del aporte de oxígeno a los órganos), lo que con frecuencia requiere soporte con terapias de rescate como inotrópicos, vasopresores o dispositivos mecánicos. Windtree Therapeutics, Inc. ha estado estudiando la istaroxima, que tiene el potencial de tratar a los pacientes en esta condición sin algunas de las desventajas de las terapias existentes utilizadas para tratar a pacientes con insuficiencia cardíaca aguda y SC. Los participantes incorporados a este ensayo recibirán terapia de cuidado estándar (SoC) para la insuficiencia cardíaca y el SC. Adicionalmente, la mitad de los participantes serán seleccionados de forma aleatoria para recibir istaroxima. La istaroxima tiene el potencial de aumentar la presión arterial y mejorar la función cardíaca.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 85 YearsSexo: ALL

Criterios de inclusión

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)

Criterios de exclusión

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:
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.

Ensayo multicéntrico, aleatorizado, controlado con placebo y de grupos paralelos sobre la seguridad y eficacia de istaroxima para el shock cardiogénico SCAI estadio C

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Istaroxime

Placebo

Ubicaciones

Sanatorio Güemes

Sanatorio De la Trinidad Palermo

Instituto Cardiovascular de Rosario

Hospital Privado de Rosario

Patrocinadores