ACTIVE_NOT_RECRUITING

A Safety and Efficacy Trial of Istaroxime for Cardiogenic Shock Stage C

Conditions

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The current trial aims to assess the effect of istaroxime in patients with SCAI Stage C Cardiogenic Shock (CS). These patients look unwell, frequently with a sudden change in mental status, mottled and cool extremities, and delayed capillary refill, as well as signs of congestion and relative low blood pressure and signs of hypoperfusion (reduced oxygen to organs) which frequently require support with rescue therapies including inotropes, vasopressors, or mechanical devices. Windtree Therapeutics, Inc. has been studying istaroxime, which has the potential to treat patients in this condition without some of the disadvantages of existing therapies being used to treat patients with acute heart failure and CS. Participants enrolled in this trial will receive standard of care (SoC) therapy for heart failure and CS. Additionally, half of the participants will be randomly chosen to receive istaroxime. Istaroxime has the potential to increase blood pressure and improve cardiac function.

Official Title

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

Quick Facts

Study Start:2024-06-01

Study Completion:2026-08-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05975021

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 85 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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). * 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 * 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)	* 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.

Inclusion Criteria

Exclusion 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).
* 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
* 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)

* 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.

Contacts and Locations

Principal Investigator

Steven G Simonson, MD

STUDY_DIRECTOR

Windtree Therapeutics, Inc.

Study Locations (Sites)

Tufts Medical Center

Boston, Massachusetts, 02111

United States

Oregon Health and Sciences University

Portland, Oregon, 97201

United States

Collaborators and Investigators

Sponsor: Windtree Therapeutics

Steven G Simonson, MD, STUDY_DIRECTOR, Windtree Therapeutics, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-06-01

Study Completion Date2026-08-31

Study Record Updates

Study Start Date2024-06-01

Study Completion Date2026-08-31

Terms related to this study

Additional Relevant MeSH Terms

Cardiogenic Shock