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Study on the Safety and Efficacy of Istaroxime for Pre-Cardiogenic Shock (SEISMiC)
||A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study on the Safety and Efficacy of Istaroxime for Pre-Cardiogenic Shock (SEISMiC)
||Gaurav Gulati, MD
This is a pilot, multinational, multicenter, randomized, double-blind, placebo-controlled, 2-part safety and efficacy study. Subjects 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] 70-100 mmHg for two hours) and heart rate 75 to 150 beats/minute. The primary objective of this study is to assess the ability of istaroxime to increase SBP in patients with cardiogenic shock (CS) or pre-shock (Society for Cardiovascular Angiography & Intervention (SCAI) Stages A and B), defined as hospitalization for ADHF with persistent hypotension (SBP 70-100 mmHg for two hours) who currently, and since admission to the hospital and throughout Screening, have not received IV vasopressors, inotropes, or digoxin, or not on cardiovascular, respiratory, or renal mechanical support.
All inclusion criteria must be met in order to be enrolled in this study (partial list): 1. Clinical presentation consistent with SCAI Stage A or 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. 2. An admission for an ADHF episode within 36 hours prior to randomization, defined as: dyspnea, at rest or with minimal exertion, and congestion on chest x-ray or lung US with 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. 3. History of left ventricular ejection fraction (LVEF) ≤ 40%; persistent hypotension defined as SBP of 70 to 100 mmHg for ≥ 2 hours prior to screening; SBP doesn’t decrease by > 7 mmHg on two separate measurements during the last 2 hours prior to randomization.
Subjects meeting any exclusion criteria must not be enrolled in this study (partial list): 1. Cardiogenic shock of SCAI stage C or worse; cardiogenic shock due to any other condition besides acute decompensation of chronic heart failure. 2. Any of the following in the past 30 days: acute coronary syndrome, coronary revascularization, MI, CABG, or percutaneous coronary intervention. History of heart transplant or UNOS priority 1a heart transplant listing. 3. Venous Lactate > 2 mmol/L; Severe renal impairment (eGFR < 30 ml/min); Suspected sepsis; fever > 38° or active infection requiring IV antimicrobial treatment; Body weight < 40 kg or ≥ 150 kg; Laboratory exclusions: Hemoglobin < 9 g/dl; Platelet count < 100,000/μl; Serum potassium > 5.3 mmol/l or < 3.5 mmol/l.
This study will consist of a screening period of up to 24 hours, a treatment period of 60 hours, including down-titration periods; a post-treatment period from Days 3 to 5 after starting study drug, and a follow-up visit at Day 30. During the screening process and the whole study, up to 45 ml (approximately 3 tablespoons) of blood will be drawn. During the treatment and post-treatment periods the study staff will frequently collect following data and perform following procedures: vital signs (includes blood pressure and pulse); body temperature; oxygen saturation (the percentage of oxygen bound to hemoglobin in the blood); urine collection for urine output volume assessment at 24, 48, and 72 hours; documentation of medications taken; ECG just prior to infusion start and at 12 and 24, 48, 72 and 96 hours; Holter monitoring for 72 hours; echocardiogram (ultrasound exam of your heart); questions about any side effects and follow up after hospital discharge.