| Eligibility |
Inclusion Criteria:
- Signed informed consent form (ICF);
- Clinical presentation consistent with SCAI Stage C cardiogenic shock caused by ADHF
and meeting the criteria in below table;
- Admitted to ICU within 36 hours prior to randomization with congestion on chest x-ray
or lung ultrasound and BNP = 400 pg/mL or NT-proBNP = 1400 pg/mL;
- Males and females, 18 to 85 years of age (inclusive);
- History of left ventricular ejection fraction (LVEF) = 40%;
- Persistent hypotension defined as SBP between 70 and 90 mmHg for 2 readings with
concomitant signs of hypoperfusion;
- Echocardiogram during initial hospitalization confirming ejection fraction = 40% and
no evidence of other pathology to confound interpretation of cardiac physiology (eg,
pericardial effusion).
Table: Definition of SCAI Stage C Required for Inclusion. These criteria must be present at
screening or prior to screening in patients actively treated by vasoactive agents or/and
inotropes concomitantly (at the same time)
Must have at Least One of:
- Hypoperfusion: Venous Lactate = 2 mmol/L, urine output < 30 mL/hour, cold and clammy
or acute alteration in mental status.
- Hemodynamic Instability: SBP 70-90 mmHg, cardiac index < 2.2 L/min/meter2 and PCW > 15
mmHg
Without Any Of:
- Venous lactate > 5 mmol/L
- Worsening clinical status despite initial therapy (e.g., worsening hemodynamics,
worsening renal or liver function)
- ALT >500 U/L (8.333 µkat/L)
Exclusion Criteria:
- Patient is in SCAI B (BP increased above 90 mmHg despite no vasoactive or inotrope
therapy) or SCAI D (continuously deteriorating BP and hypoperfusion despite vasoactive
or inotrope therapy);
- Lactate < 2 mmol/L (unless the patient meets the criteria in bullet 2 of Table 5-1) or
lactate > 5 mmol/L prior to randomization;
- Cardiogenic shock due to any other condition besides acute decompensation of chronic
heart failure;
- Any of the following in the past 30 days: acute coronary syndrome, coronary
revascularization, MI, CABG, or percutaneous coronary intervention;
- Current (within 6 hours of screening) or anticipated need for treatment with renal
support including ultrafiltration, or mechanical circulatory, ventilatory or renal
support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation,
or any ventricular assist device) such as persistent hypoperfusion and hypotension;
- History of heart transplant or UNOS priority 1a heart transplant listing
- 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 (eGFR < 30 ml/min, calculated by the MDRD formula);
- Hypersensitivity to the trial medication and its excipients (including known lactose
hypersensitivity) or any related medication;
- Stroke or TIA within 3 months;
- Severe obstructive valvular lesions including severe aortic or mitral stenosis;
- 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 (inclusive of atrial fibrillation as the main reason for admission),
infection, severe anemia, acute coronary syndrome, pulmonary embolism, exacerbation of
COPD, planned admission for device implantation, or over-diuresis as a cause of
hypotension;
- Pericardial constriction or active pericarditis;
- Significant ventricular arrhythmia prior to screening (such as sustained ventricular
tachycardia or ventricular fibrillation) 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;
- Uncontrolled arrythmia;
- Sustained hypotension (SBP < 70 mmHg) for at least 30 minutes from the time of arrival
to the hospital;
- Systolic BP > 120 mmHg during the hour prior to randomization
- Cor pulmonale or other causes of isolated right-sided HF or not related to left
ventricular dysfunction;
- Acute respiratory distress syndrome;
- Suspected sepsis; fever > 38° or active infection requiring IV antimicrobial
treatment;
- Body weight < 40 kg or = 150 kg;
- Laboratory exclusions:
1. Hemoglobin < 9 g/dl,
2. Platelet count < 100,000/µl,
3. Serum potassium > 5.3 mmol/l or < 3.5 mmol/l;
- A life expectancy < 3 months based on the judgment of the investigator;
- Severe pulmonary or thyroid disease;
- Pregnant, planning on becoming pregnant, or currently breast-feeding;
- Ongoing drug or alcohol abuse;
- Participation in another interventional trial within the past 30 days.
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