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

NCT05975021 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 04-CL-2201CT Id: 2023-507243-11-00
• Study Type: interventional
• Target: 20
• Locations: 5 countries
• Sites: 15

Brief Summary

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.

Conditions

Cardiogenic Shock

Outcome Measures

Primary Outcomes (1)

• SBP AUC 0-6

  Systolic blood pressure (SBP) area under the curve (AUC) from start of infusion to 6 hours

  Start of infusion to 6 hours

Study Arms (2)

Istaroxime

EXPERIMENTAL

Istaroxime delivered as an IV infusion via a syringe pump. Dosage regime is 1.0 µg/kg/min for 6 hours, 0.5 µg/kg/min for 42 hours. Total duration 48 hours.

Drug: Istaroxime

Placebo

PLACEBO COMPARATOR

Placebo (lactose) delivered as an IV infusion via a syringe pump. Total duration 48 hours.

Drug: Placebo

Interventions

Istaroxime DRUG

IV infusion via a syringe pump. Dosage of 1.0 µg/kg/min for 6 hours; 0.5 µg/kg/min for 42 hours. Total duration 48 hours.

Also known as: PST2744

Istaroxime

Placebo DRUG

IV infusion via a syringe pump. Total duration 48 hours.

Also known as: Lactate

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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)

You may not qualify if:

• 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;

Sponsors & Collaborators

• Windtree Therapeutics: lead

Study Sites (15)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Oregon Health and Sciences University

Portland, Oregon, 97201, United States

Location

Sanatorio Güemes

Capital Federal, Buenos Aires, 1180, Argentina

Location

Sanatorio De la Trinidad Palermo

Capital Federal, Buenos Aires, 1425, Argentina

Location

Instituto Cardiovascular de Rosario

Rosario, Sante Fe, S2000DSR, Argentina

Location

Hospital Privado de Rosario

Rosario, Sante Fe, S2000GAP, Argentina

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo

Alessandria, 15121, Italy

Location

ASST degli Spedali Civili di Brescia

Brescia, 25123, Italy

Location

IRCCS San Raffaele Scientific Institute

Milan, 20132, Italy

Location

University of Turin, Città della Salute e della Scienza

Turin, 10123, Italy

Location

Uniwersytecki Szpital Kliniczny w Białymstoku

Bialystok, 15-276, Poland

Location

Uniwersytecki Szpital Kliniczny w Opolu

Opole, 45-401, Poland

Location

Uniwersytecki Szpital Kliniczny, Instytut Chorob Serca

Wroclaw, 50-556, Poland

Location

4 Wojskowy Szpital Kliniczny z Polikliniką SP ZOZ

Wroclaw, 50-981, Poland

Location

MeSH Terms

Conditions

Shock, Cardiogenic

Interventions

Istaroxime; Lactic Acid

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Shock

Intervention Hierarchy (Ancestors)

Lactates; Hydroxy Acids; Carboxylic Acids; Organic Chemicals

Study Officials

• Steven G Simonson, MD

  Windtree Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Trial treatment will be blinded to the trial staff. Istaroxime and placebo are both lyophilized powders and are put into identical vials. Each trial box will be numbered with a unique identifier, which will not allow the trial staff to ascertain which treatment is being used.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a pilot, multinational, multicenter, randomized, double-blind, placebo-controlled, safety and efficacy trial. Participants 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 to 90 mmHg for two readings with concomitant signs of hypoperfusion), and mild to moderate renal impairment.

Study Record Dates

• First Submitted: July 26, 2023
• First Posted: August 3, 2023
• Study Start: June 1, 2024
• Primary Completion: July 28, 2025
• Study Completion (Estimated): August 31, 2026
• Last Updated: August 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: 6 months after study end.
• Access Criteria: Mutual written agreement.

Locations

IL (1); AR (4); IT (4); US (2); PL (4)