SEISMiC: The Safety and Efficacy of Istaroxime for Pre-Cardiogenic Shock
Study Details
Study Description
Brief Summary
This is a pilot, multinational, randomized, double-blind, placebo-controlled safety and efficacy study. Subjects will consist of patients hospitalized for acute decompensated heart failure with persistent hypotension and heart rate 75 to 150 beats/minute.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a pilot, multinational, multicenter, randomized, double-blind, placebo-controlled, safety and efficacy study. Subjects will consist of males or females 18 to 85 years of age hospitalized for ADHF with persistent hypotension (systolic blood pressure [SBP] 75 to 90 mmHg for two hours), and heart rate 75 to 150 beats/minute.
Subjects will be enrolled into one of two groups in a 1:1 ratio: istaroxime or matching placebo, administered via 24-hour intravenous (IV) infusion. Istaroxime administration can begin at 1.0 or 1.5 µg/kg/min; the target infusion rate is 1.5 µg/kg/min. All subjects will receive standard of care.
Approximately 30 sites from North America, South America, Europe, and/or Asia will participate in this study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Istaroxime 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
Reconstituted istaroxime and lactose lyophilized powder delivered via IV infusion
Other Names:
|
| Placebo Comparator: Placebo Placebo (lactose lyophilized powder) IV infusion for 24 hours |
Drug: Placebo
Reconstituted placebo (lactose lyophilized powder) delivered via IV infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change from baseline in systolic blood pressure (SBP) area under the curve (AUC)₀-₆ [6 hours after initiation of infusion]
Change from baseline in AUC for systolic blood pressure measured via a sphygmomanometer or arterial line
Secondary Outcome Measures
- Treatment failure score [24 hours from initiation of infusion]
Treatment-failure score, based on death, circulatory, respiratory or renal mechanical support or IV inotrope or vasopressor treatment, and changes in systolic blood pressure
- Treatment failure score [72 hours from initiation of infusion]
Treatment-failure score, based on death, circulatory, respiratory or renal mechanical support or IV inotrope or vasopressor treatment, and changes in systolic blood pressure
- Change from baseline in SBP [4 hours after initiation of infusion]
Change from baseline in systolic blood pressure measured via a sphygmomanometer or arterial line
- Change from baseline in SBP [24 hours after initiation of infusion]
Change from baseline in systolic blood pressure measured via a sphygmomanometer or arterial line
- Change from baseline in SBP AUC₀-₂₄ [24 hours after initiation of infusion]
Change from baseline in AUC for systolic blood pressure measured via a sphygmomanometer or arterial line
- Number of participants with SBP increases > 10 mmHg [Up to 24 hours after initiation of infusion]
Change from baseline in systolic blood pressure measured via a sphygmomanometer or arterial line
- Number of participants with SBP increases > 5% from baseline value [Up to 24 hours after initiation of infusion]
Change from baseline in systolic blood pressure measured via a sphygmomanometer or arterial line
- Change from baseline in quality of life: EQ-5D [Day 4 from randomization]
Changes from baseline measured by the EQ-5D
- Change from baseline in quality of life: EQ-5D [Day 30 from randomization]
Changes from baseline measured by the EQ-5D
- Change from baseline in creatinine clearance [24 hours from randomization]
Change from baseline in creatinine clearance based on laboratory analysis
- Change from baseline in creatinine clearance [48 hours from randomization]
Change from baseline in creatinine clearance based on laboratory analysis
- Change from baseline in creatinine clearance [72 hours from randomization]
Change from baseline in creatinine clearance based on laboratory analysis
- Change from baseline in creatinine clearance [96 hours from randomization]
Change from baseline in creatinine clearance based on laboratory analysis
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Signed informed consent form (ICF);
-
Males and females, 18 to 85 years of age (inclusive);
-
An admission within 36 hours prior to randomization for acute decompensated heart failure (ADHF) episode, 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 N-terminal-pro hormone BNP (NT-proBNP) ≥ 1400 pg/mL;
-
History of left ventricular ejection fraction (LVEF) < 40%;
-
Persistent hypotension defined as:
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SBP between 75 and 90 mmHg for at least 2 hours prior to Screening;
-
SBP doesn't 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 confirming ejection fraction < 40% and no evidence of other pathology to confound interpretation of cardiac physiology (eg, pericardial effusion).
Exclusion Criteria:
-
Current treatment (within 6 hours of Screening) 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);
-
Lactate > 2 mmol/L;
-
History of heart transplant or priority 1a heart transplant listing (United Network for Organ Sharing; UNOS)
-
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 related medication;
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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;
-
Stroke or transient ischemic attack (TIA) within 3 months;
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Incomplete revascularization (patients with ischemic heart disease have to have had a catheterization in the last year demonstrating that the main coronary arteries are well revascularized);
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Moderate or severe valvular disease, such as severe Aortic 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, 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;
-
Life-threatening ventricular arrhythmia or implantable cardioverter defibrillator (ICD) shock within the past month or history of sudden death within 6 months;
-
Cardiac resynchronization therapy (CRT), ICD, or pacemaker implantation within the past month;
-
Sustained ventricular tachycardia in the last 3 months with no defibrillator;
-
Cor pulmonale or other causes of isolated right-sided HF or not related to left ventricular dysfunction;
-
Acute respiratory distress syndrome;
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Suspected sepsis; fever > 38° or active infection requiring IV antimicrobial treatment;
-
Body weight < 40 kg or ≥ 130 kg;
-
Laboratory exclusions:
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Hemoglobin < 9 g/dl,
-
Platelet count < 100,000/µl,
-
Serum potassium > 5.3 mmol/l or < 3.5 mmol/l;
-
Cirrhosis or malignancy with a life expectancy < 3 months;
-
Severe pulmonary or thyroid disease;
-
Pregnant or breast-feeding;
-
Ongoing drug or alcohol abuse;
-
Participation in another interventional study within the past 30 days.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tennessee Center for Clinical Trials | Tullahoma | Tennessee | United States | 37388 |
| 2 | Uniwersytecki Szpital Kliniczny, Centrum Chorub Serca | Wrocław | Dolnoslaskie | Poland | 50-556 |
| 3 | Szpital Uniwersytecki Kliniczny Oddzial Kardiologii | Zielona-Góra | Lubuskie | Poland | 65-046 |
| 4 | Szpital Jana Pawła II | Krakow | Malopolskie | Poland | 31-202 |
| 5 | Moscow State Budgetary Institution of Healthcare "City Clinical Hospital Named after VV Vinogradov" by Moscow Department of Healthcare | Moscow | Russian Federation | 117292 | |
| 6 | MSBIH "City Clinical Hospital 52 by Moscow Department of Healthcare" | Moscow | Russian Federation | 123182 | |
| 7 | City Clinical Hospital Named after VV Veresaev | Moscow | Russian Federation | 127644 | |
| 8 | State Budgetary Institution "Saint-Petersburg Scientific Research Institute of Emergency Care named after I.I. Dzhanelidze" | Saint Petersburg | Russian Federation | 192242 |
Sponsors and Collaborators
- Windtree Therapeutics
- Momentum Research, Inc.
Investigators
- Principal Investigator: Marco Metra, MD, Università degli Studi di Brescia
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 04-CL-1904