The Safety and Efficacy of Istaroxime for Pre-Cardiogenic Shock

NCT04325035 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 04-CL-19042020-000885-40
• Study Type: interventional
• Target: 90
• Locations: 4 countries
• Sites: 13

Brief Summary

This is a pilot, multinational, randomized, double-blind, placebo-controlled, 2-part safety and efficacy study. Subjects will consist of patients hospitalized for acute decompensated heart failure with persistent hypotension.

Conditions

Cardiogenic Shock

Keywords

Pre-cardiogenic shock; Heart failure

Outcome Measures

Primary Outcomes (1)

• Change from baseline in systolic blood pressure (SBP) area under the curve (AUC) 0-6

  Change from baseline AUC for systolic blood pressure

  0 to 6 hours after initiation of infusion

Secondary Outcomes (29)

• Change from baseline in SBP AUC 0-48

  0 to 60 hours after initiation of infusion

• Change from baseline in SBP AUC 0-60

  0 to 48 hours after initiation of infusion

• Treatment failure score

  60 hours from initiation of infusion

• Change from baseline in SBP

  6 hours after initiation of infusion

• Change from baseline in SBP

  24 hours after initiation of infusion

Study Arms (5)

Istaroxime - Part A

EXPERIMENTAL

Istaroxime IV infusion for 24 hours. Istaroxime administration can begin at 1.0 or 1.5 µg/kg/min; the target infusion rate is 1.5 µg/kg/min

Drug: Istaroxime

Placebo - Part A

PLACEBO COMPARATOR

Placebo (lactose lyophilized powder) IV infusion for 24 hours

Drug: Placebo

Istaroxime - Part B

EXPERIMENTAL

Istaroxime IV infusion at 1.0 µg/kg/min for 6 hours, 0.5 µg/kg/min for 42 hours, 0.25 µg/kg/min for 12 hours.

Drug: Istaroxime

Istaroxime and Placebo - Part B

EXPERIMENTAL

Istaroxime IV infusion at 0.5 µg/kg/min for 48 hours, followed by placebo IV infusion for 12 hours.

Drug: Istaroxime; Drug: Placebo

Placebo - Part B

PLACEBO COMPARATOR

Placebo (lactose lyophilized powder) IV infusion for 60 hours.

Drug: Placebo

Interventions

Istaroxime DRUG

Reconstituted istaroxime and lactose lyophilized powder delivered via IV infusion

Also known as: PST2744

Istaroxime - Part A; Istaroxime - Part B; Istaroxime and Placebo - Part B

Placebo DRUG

Reconstituted placebo (lactose lyophilized powder) delivered via IV infusion

Also known as: Lactose lyophilized powder

Istaroxime and Placebo - Part B; Placebo - Part A; Placebo - Part B

Eligibility Criteria

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

You may qualify if:

• Clinical presentation consistent with SCAI Stage B pre-cardiogenic shock caused by acute decompensation of chronic systolic heart failure (due to arterial hypertension, ischemic heart disease or dilated cardiomyopathy), without evidence for an acute coronary syndrome.
• Signed informed consent form (ICF);
• Males and females, 18 to 85 years of age (inclusive);
• An admission for acute decompensated heart failure (ADHF) episode within 36 hours prior to randomization, defined as:
• Dyspnea, at rest or with minimal exertion;
• Congestion on chest x-ray or lung US with B-type natriuretic peptide (BNP) ≥ 400 pg/mL or NT-proBNP ≥ 1400 pg/mL; Elective admissions for medications tune up or procedures do not qualify as an ADHF admission.
• History of left ventricular ejection fraction (LVEF) ≤ 40%;
• Persistent hypotension defined as:
• SBP of 75 to 90 mmHg (Part A) or 70 to 100 mmHg (Part B) for ≥ 2 hours prior to Screening;
• SBP does not decrease by \> 7 mmHg on two separate measurements during the last 2 hours prior to randomization;
• Heart rate 75 to 150 bpm. If the subject is on a beta-blocker, the range is 60 to 150 bpm;
• Echocardiogram during initial hospitalization confirming ejection fraction ≤ 40% and no evidence of other pathology to confound interpretation of cardiac physiology (e.g., pericardial effusion);
• Subject is monitored by a Pulmonary Artery Catheter (PAC) at the time of randomization (Part B only).

You may not qualify if:

• Cardiogenic shock of SCAI Stage C or worse
• 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, myocardial infarction (MI), coronary artery bypass graft (CABG), or percutaneous coronary intervention;
• Current (within 6 hours of Screening) or anticipated need for treatment 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);
• Venous Lactate \> 2 mmol/L;
• History of heart transplant or United Network for Organ Sharing (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 (estimated glomerular filtration rate (eGFR) \< 30 ml/min, calculated by the Modification of Diet in Renal Disease (MDRD) formula);
• Hypersensitivity to the study medication or any of its excipients (including known lactose hypersensitivity) or any related medication;
• Stroke or transient ischemic attack (TIA) within 3 months;
• Active coronary ischemia;
• Any significant valvular disease (including any moderate or severe valvular stenosis, moderate or severe aortic or pulmonary regurgitation, stenosis or regurgitation);severe tricuspid or mitral regurgitation);
• 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 chronic obstructive pulmonary disease (COPD), planned admission for device implantation, or over-diuresis as a cause of hypotension;
• Pericardial constriction or active pericarditis;

Sponsors & Collaborators

• Windtree Therapeutics: lead
• Momentum Research, Inc.: collaborator

Study Sites (13)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Hospital Italiano de Bueno Aires

Capital Federal, Buenos Aires, C1199, Argentina

Location

Santorio Guemes

Capital Federal, Buenos Aires, CP1180, Argentina

Location

Hospital Privado de Rosario

Rosario, Sante Fe, S20000GAP, Argentina

Location

Instituto Cardiovascular de Rosario

Rosario, Sante Fe, S2000DSR, Argentina

Location

Santorio de la Trinidad Palermo

Buenos Aires, C1425, Argentina

Location

Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo

Alessandria, Italy

Location

UOC Cardiologia, ASST degli Spedali Civili di Brescia Pizzale Spedali Civili 1

Brescia, 25123, Italy

Location

IRCCS San Raffaele Scientific Institute

Milan, 20132, Italy

Location

Uniwersytecki Szpital Kliniczny, Centrum Chorub Serca

Wroclaw, Lower Silesian Voivodeship, 50-556, Poland

Location

Uniwersytecki Szpital Kliniczny w Białymstoku

Bialystok, 15-276, Poland

Location

Uniwersytecki Szpital Kliniczny w Opolu

Opole, 45-401, Poland

Location

4 Wojskowy Szpital Kliniczny

Wroclaw, 50-981, Poland

Location

Related Publications (2)

• Metra M, Chioncel O, Cotter G, Davison B, Filippatos G, Mebazaa A, Novosadova M, Ponikowski P, Simmons P, Soffer J, Simonson S. Safety and efficacy of istaroxime in patients with acute heart failure-related pre-cardiogenic shock - a multicentre, randomized, double-blind, placebo-controlled, parallel group study (SEISMiC). Eur J Heart Fail. 2022 Oct;24(10):1967-1977. doi: 10.1002/ejhf.2629. Epub 2022 Aug 22.

  PMID: 35867804 RESULT

• Metra M, Chioncel O, Davison B, Filippatos G, Mebazaa A, Pagnesi M, Adamo M, Novosadova M, Ponikowski P, Simmons P, Soffer J, Simonson S, Cotter G. Safety and Efficacy of Istaroxime 1.0 and 1.5 microg/kg/min for Patients With Pre-Cardiogenic Shock. J Card Fail. 2023 Jul;29(7):1097-1103. doi: 10.1016/j.cardfail.2023.03.020. Epub 2023 Apr 17.

  PMID: 37075941 RESULT

MeSH Terms

Conditions

Shock, Cardiogenic; Heart Failure

Interventions

Istaroxime

Condition Hierarchy (Ancestors)

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

Study Officials

• Marco Metra, MD

  Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Matching Placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2020
• First Posted: March 27, 2020
• Study Start: September 28, 2020
• Primary Completion: September 26, 2024
• Study Completion: October 30, 2024
• Last Updated: February 4, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

PL (4); AR (5); US (1); IT (3)