Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.
Primary outcome(s):
ICU discharge mortality
This will be assessed based on the patient’s vital status at the time of leaving the unit. The clinical outcome will be recorded, classifying the patient as alive or deceased at ICU discharge, regardless of the length of stay.
Key secondary outcomes:
"Improvement and/or recovery of biventricular systolic-diastolic function. Ventricular function will be assessed through echocardiographic tests. Measurement times will be: at inclusion, daily during the first 72 hours, on treatment days 5, 7, and 10, at ICU discharge (when individualized response for each function is evaluated), and finally at hospital discharge. The parameters to be measured are:
• Left ventricular systolic function:
o LVEF (Simpson)
o Ao VTI
o Lateral MAPSE
o S′
• Left ventricular diastolic function:
o e′
o E/e′
o E/A
• Right ventricular systolic function:
o TAPSE
o S′"
• Improvement of organ function. This will be determined by the delta SOFA 2, defined as the difference between the maximum score recorded during the first 72 hours of treatment and the score obtained at the end of treatment. Evaluation will be performed daily during the first 72 hours, then on days 5, 7, and 10, as well as at ICU discharge and at hospital discharge. The systems to be evaluated will be:
o Respiratory: Partial pressure of oxygen / fraction of inspired oxygen (PO2/FiO2) and oxygen saturation / fraction of inspired oxygen (SpO2/FiO2).
o Renal: Creatinine / Diuresis
o Hepatic: Total bilirubin
o Cardiovascular: Mean arterial pressure (MAP) or drugs
o Hematologic: Platelet count
oNeurologic: Glasgow Coma Scale
• Hospital discharge mortality. This will be assessed based on the patient’s vital status at the time of leaving the hospital, classifying the patient as alive or deceased at hospital discharge, regardless of the length of stay in the healthcare facility.
• Safety: The presence of adverse events will be evaluated through physical examination and laboratory tests:
o Clinical adverse events: The type, duration, intensity, causal relationship, management, and outcome will be described. For this purpose, the patient will be evaluated through interview, physical examination, and monitoring of organ functions, at least daily during hospitalization, but also at any other time when an adverse event occurs and up to 48 hours after completion of the investigational treatment.
o Vital signs: Blood pressure, heart rate, respiratory rate, and axillary temperature. Vital signs will be recorded at baseline (before administration of the investigational product) and after initiation of treatment: at 30 minutes, 1 hour, 2 hours, and subsequently every 8 hours while the patient remains in the ICU. After ICU discharge, they will be taken during each daily assessment in the ward of the service to which the patient is referred until medical discharge. This monitoring may be performed more frequently if any abnormality is detected.
o Laboratory tests (hematological and biochemical): These determinations will be performed in the clinical laboratories of each hospital. Blood samples will be collected at baseline (before the first administration of the investigational product), daily during the first 72 hours after treatment initiation, then on days 5, 7, and 10, at ICU discharge (24–48 hours after the last administration of the investigational product), and at hospital discharge.
1. Hematology: Platelet count.
2. Blood gas analysis: Partial pressure of oxygen (PO2), oxygen saturation (SpO2), and fraction of inspired oxygen (FiO2).
3. Blood biochemistry: Creatinine and total bilirubin.
4. Biological markers of cardiac necrosis and ventricular dysfunction (in heparinized venous blood): Troponin, CK, CK-MB, and NT-proBNP. These tests will be performed in patients included at the CIMEQ clinical site at three time points: baseline (prior to administration of the investigational product), on day 3, and on day 10.
