Randomized Evaluation of Istaroxime for Stabilization in Acute Heart Failure-Cardiogenic Shock

NCT07583446 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: Seismic-Ista-001
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if the drug istaroxime works to treat cardiogenic shock due to acute heart failure in adults. It will also learn about the safety of istaroxime. Researchers will compare istaroxime to a placebo (a look-alike substance that contains no drug) to see if istaroxime works to treat cardiogenic shock due to acute heart failure. The main questions it aims to answer are:

• Does istaroxime relieve participants' shortness of breath compared to a placebo?
• Does istaroxime provide clinical benefit in terms of lowering the risk of dying, having invasive procedures, being rehospitalized or having worsening heart failure, and/or increasing quality of life compared to a placebo?
• Does istaroxime reduce the duration of the initial hospital stay compared with placebo? Participants will:
• Receive a 48-hour intravenous infusion of istaroxime or placebo with possible additional retreatment depending on their clinical condition
• Complete questionnaires rating their breathing and describing their quality of life
• Return for visits 30 and 90 days after the start of Cycle 1 infusion. The trial will end when the last participant completes Day 30 and all participants have been followed for at least 30 days after their last IMP exposure. At trial termination, participants who have not been followed to Day 90 will have an end-of-study (EOS) visit.

Conditions

Cardiogenic Shock

Outcome Measures

Primary Outcomes (2)

• Change in participant-reported dyspnea

  Area under the curve (AUC) of change from baseline in dyspnea visual analog scale (VAS) score (0-100; higher scores indicate better breathing).

  24 hours

• Hierarchical composite endpoint

  Hierarchical composite of (1) time to all-cause death; (2) time to first initiation of new mechanical circulatory support, urgent durable LVAD implantation or heart transplantation, or invasive mechanical respiratory support; (3) time to first heart failure rehospitalization or worsening heart failure; and (4) change from baseline in EQ-VAS score (0-100; higher scores indicate better health).

  30 days; EQ-VAS change from baseline to 48 hours

Secondary Outcomes (1)

• Length of hospital stay

  30 days

Study Arms (2)

istaroxime

EXPERIMENTAL

Participants will receive istaroxime by continuous intravenous infusion.

Drug: istaroxime

placebo

PLACEBO COMPARATOR

Participants will receive placebo (normal saline) by continuous intravenous infusion.

Drug: placebo

Interventions

istaroxime DRUG

intravenous istaroxime

istaroxime

placebo DRUG

intravenous placebo

placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged between 18 and 80 years old (inclusive) at the time of informed consent, regardless of gender.
• Diagnosed with CS due to AHF during screening, before randomization, and meeting all of the following criteria:
• Dyspnea at rest or with minimal activity before screening and randomization.
• Pulmonary rales, or lower limb edema by physical examination.
• Evidence of pulmonary congestion by chest X-ray, CT scan or lung ultrasound
• At the time of screening and just prior to randomization either:
• systolic BP ≤ 100 mmHg or
• systolic BP ≤ 115 mmHg and \>100 mmHg accompanied by at least one sign of hypoperfusion or hemodynamic compromise: cool extremities, altered mentation attributable to low output, oliguria, elevated lactate (\>2 mmol/L), worsening renal function attributable to low perfusion, or invasive/noninvasive hemodynamic evidence of reduced cardiac output.
• Initial hospitalization (defined as first medical contact in the hospital) for this AHF event within 20 hours before randomization.
• Documented history within 6 months prior to screening, or during the current admission, of left ventricular ejection fraction (LVEF) \< 40%.
• N-terminal pro-B-type natriuretic peptide (NT-proBNP) \> 1,500 pg/mL or BNP \> 400 pg/mL during screening, before randomization.
• Signed informed consent, including compliance with the requirements and restrictions listed in the informed consent form (ICF) and the study protocol.

You may not qualify if:

• Body weight \< 40 kg or ≥ 150 kg at Screening.
• Rapidly deteriorating cardiogenic shock requiring escalating support
• Patients with any systolic blood pressure measurement \>130 mmHg within 2 hours prior to randomization.
• Administration during the 6 hours prior to screening of vasodilators such as nitroglycerin, nitrates, recombinant human brain natriuretic peptide.
• Received digoxin within 7 days before randomization.
• Taking a medication that is a substrate of cytochrome P450 2C19 (CYP2C19).
• Patients with severe lung disease (dependent on oral steroids or immunosuppressive therapy or require home oxygen therapy), respiratory failure, or severe pulmonary hypertension.
• Acute ischemic or hemorrhagic cerebral infarction or transient ischemic attack within 30 days before screening.
• Abnormal laboratory findings including during screening:
• Renal impairment (eGFR \< 25 ml/min/1.73 m2) or the need for long-term or intermittent renal support therapy (hemodialysis, ultrafiltration or peritoneal dialysis);
• Severe electrolyte imbalance (Na+ \<120mmol/L or \>160mmol/L, and/or K+ \<3.2mmol/L or \>5.5mmol/L);
• Liver function impairment (ALT and/or AST \> 3 times the upper limit of the normal range and/or bilirubin exceeds 1.5 times the upper limit of the normal range); or
• Hemoglobin \<9 g/dL (\<5.6 mmol/L).
• Severe valvular stenosis that has not been surgically corrected, or moderate or severe aortic regurgitation.
• Obstructive hypertrophic cardiomyopathy or restrictive cardiomyopathy, constrictive pericarditis, cardiac tamponade, cardiomyopathy based on infiltrative disease (such as amyloidosis), accumulation disease (such as hemochromatosis, Fabry disease), myocardial dysplasia, cardiomyopathy caused by reversible causes (such as stress cardiomyopathy) or acute myocarditis.

Sponsors & Collaborators

• Seismic Pharmaceuticals Operations LLC: lead

Study Sites (1)

Institute of Surgery Mikayelyan CJSC

Yerevan, 0052, Armenia

RECRUITING

MeSH Terms

Conditions

Shock, Cardiogenic

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

• Gabe Coitler

  Seismic Pharmaceuticals

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gad Cotter, MD

CONTACT

919-317-2993; Meghnapatel@momentum-research.com

Study Design

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

Study Record Dates

• First Submitted: May 1, 2026
• First Posted: May 13, 2026
• Study Start: September 9, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 23, 2026

Record last verified: 2026-09

Locations

AR (1)