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

NCT07583446 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: Seismic-Ista-001
• Study Type: interventional
• Target: 600
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn if the drug istaroxime works to treat mild to moderate cardiogenic shock due to acute heart failure in adults. It will also learn about the safety of istaroxime. 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, having worsening heart failure, and/or increasing quality of life compared to a placebo?
• Does istaroxime increase blood pressure compared to a placebo? Researchers will compare istaroxime to a placebo (a look-alike substance that contains no drug) to see if istaroxime works to treat mild to moderate cardiogenic shock due to acute heart failure. Participants will:
• Receive a 48-hour intravenous infusion of istaroxime or placebo
• Complete questionnaires rating their breathing and describing their quality of life
• Return for a visit 30 and 90 days after the initial drug infusion was started

Conditions

Cardiogenic Shock

Outcome Measures

Primary Outcomes (3)

• Change in systolic BP

  24 hours

• composite outcome

  Hierarchical composite of death, mechanical circulatory support, worsening heart failure, quality of life assessed using the 'win ratio' method. Quality of life measured on a scale from 0=worst to 100=best. Measured using the percentage of wins among all possible comparisons between patients.

  30 days

• shortnes of breath

  Measured on a scale from 0=worst to 100=best breathing

  24 hours

Secondary Outcomes (1)

• lenght of hospital stay

  30 days

Study Arms (2)

istaroxime

EXPERIMENTAL

Drug: istaroxime

placebo

PLACEBO COMPARATOR

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 SCAI B or C due to AHF during screening, before randomization, as defined by:
• 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.
• Admitted for AHF 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%.
• New York Heart Association (NYHA) functional class ≥ II at 1 month prior to admission.
• 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 as described in Section 11.3 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

You may not qualify if:

• Body weight \< 40 kg or ≥ 150 kg at Screening.
• Society for Cardiovascular Angiography and Interventions (SCAI) level D or more severe cardiogenic shock during screening, prior to randomization.
• 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
• Prescription of digoxin within 7 days before randomization.
• 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);
• Hemoglobin \<9 g/dL (\<5.6 mmol/L).
• Severe valvular stenosis that has not been surgically corrected, or moderate or severe aortic or pulmonary 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.
• Sustained ventricular tachycardia or ventricular fibrillation within 30 days of screening and randomization.

Sponsors & Collaborators

• Seismic Pharmaceuticals Operations LLC: lead

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

Central Study Contacts

Gad Cotter MD, MD

CONTACT

9195990939; gadcotter@seismicrx.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• 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 (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 13, 2026

Record last verified: 2026-05