Safety and efficacy of up to 60 h of iv istaroxime in pre‐cardiogenic shock patients: Design of the SEISMiC trial

• Published in: ESC Heart Failure Vol. 12; no. 1; pp. 189 - 198
• Main Authors: Biegus, Jan, Mebazaa, Alexander, Metra, Marco, Pagnesi, Matteo, Chioncel, Ovidiu, Davison, Beth, Filippatos, Gerasimos, Tycińska, Agnieszka, Novosadova, Maria, Gulati, Gaurav, Barros, Marianela, Diaz, Maria Luz, Guardia, Carlos, Zymliński, Robert, Gajewski, Piotr, Ponikowski, Piotr, Simmons, Phillip, Simonson, Steven, Cotter, Gad
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.02.2025; John Wiley and Sons Inc; Wiley
• Subjects: Acute coronary syndromes; Blood Pressure; Cardiac arrhythmia; cardiac calcitrope; cardiogenic shock; Cardiomyopathy; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - adverse effects; Cardiovascular disease; central haemodynamics; Double-Blind Method; Drug dosages; Ejection fraction; Etiocholanolone - administration & dosage; Etiocholanolone - adverse effects; Etiocholanolone - analogs & derivatives; Female; Heart failure; Heart rate; Heart transplants; Hemodynamics - drug effects; Humans; Hypotension; Informed consent; Infusions, Intravenous; inotrope; istaroxime; Lactose; Male; Middle Aged; Multicenter Studies as Topic; Pilot Projects; pre‐cardiogenic shock; Randomized Controlled Trials as Topic; Shock, Cardiogenic - drug therapy; Shock, Cardiogenic - physiopathology; Study Design; Time Factors; Treatment Outcome; cardiogenic shock; pre‐cardiogenic shock; istaroxime; central haemodynamics; inotrope; cardiac calcitrope
• ISSN: 2055-5822; 2055-5822
• DOI: 10.1002/ehf2.15102

Aims Cardiogenic shock (CS) is linked to high morbidity and mortality rates, posing a challenge for clinicians. Interventions to improve tissue perfusion and blood pressure are crucial to prevent further deterioration. Unfortunately, current inotropes, which act through adrenergic receptor stimulation, are associated with malignant arrhythmias and poorer outcomes. Due to its unique mechanism of action, istaroxime should improve haemodynamics without adrenergic overactivation. The SEISMiC study is designed to examine the safety and efficacy (haemodynamic effect) of istaroxime administrated in pre‐CS patients. Methods and Results The SEISMiC study is a multinational, multicentre, randomized, double‐blind, placebo‐controlled safety and efficacy study with two parts (A and B). The study enrols patients hospitalized for decompensated heart failure (pre‐CS, not related to myocardial ischaemia) with persistent hypotension [systolic blood pressure (SBP) 70–100 mmHg for at least 2 h] and clinically confirmed congestion, NT‐proBNP ≥1400 pg/mL, and LVEF≤40%. Subjects must not have taken intravenous (iv) vasopressors, inotropes or digoxin in the past 6 h. Eligible patients are randomized to receive IV infusion of istaroxime (different doses and regimens in Parts A and B) or placebo for up to 60 h. Central haemodynamics, ECG Holter monitoring, cardiac ultrasound and biomarkers are recorded at predefined time points during the trial. The study's primary efficacy endpoint is the SBP area under the curve from baseline curve from baseline to 6 and 24 h in the combined SEISMiC Parts A and B population. Key secondary efficacy endpoints include haemodynamic, laboratory and clinical measures in SEISMiC B alone in the combined SEISMiC A and B studies. Conclusions The study results will contribute to our understanding of the role of istaroxime in pre‐CS patients and potentially provide insight into the drug's haemodynamic effects and safety in this population.