Extracellular Vesicle Treatment for Acute Respiratory Distress Syndrome (ARDS) (EXTINGUISH ARDS)

This is an interventional treatment trial for Acute Respiratory Distress Syndrome focused on measuring ExoFlo, Extracellular Vesicles, Exosome, ARDS Read More

INCLUSION CRITERIA:

1. Admitted to hospital with symptoms suggestive of COVID-19 infection.
2. Subject (or legally authorized representative) provides informed consent prior to the initiation of any study procedures.
3. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
4. Male or nonpregnant female aged 18-85 of age at time of enrollment.
5. Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from time of screening through Day 61.

6. Meets criteria for either severe or critical COVID-19 as evidenced by

   a. Severe COVID-19:

   i. SARS-CoV-2 PCR positive in sample collected within one week prior to randomization ii. Severe symptoms suggestive of severe systemic illness with COVID-19, which could include any symptom of moderate illness or shortness of breath at rest, or respiratory distress iii. Clinical signs indicative of severe systemic illness with COVID-19, such as respiratory rate ≥ 30 per minute, heart rate ≥ 125 per minute, SpO2 ≤ 93% on room air at sea level

   b. Critical COVID-19:

   i. SARS-CoV-2 PCR positive in sample collected within one week prior to randomization

   ii. Evidence of critical illness, defined by at least one of the following:

   • Respiratory failure defined based on resource utilization requiring at least one of the following: Endotracheal intubation and mechanical ventilation, oxygen delivery by high flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates > 20 L/min with fraction of delivered oxygen ≥ 0.5), oxygen delivery by high flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates > 20 L/min with fraction of delivered oxygen ≥ 0.5), noninvasive positive pressure ventilation, or clinical diagnosis of respiratory failure (i.e. clinical need for one of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation).
   • Shock (defined by systolic blood pressure < 90 mmHg, or diastolic blood pressure 60 mmHg or requiring pressors)
   • Multi-organ dysfunction/failure
7. PaO2/FiO2 (P/F ratio) ≤ 200.

Note for Inclusion Criterion #7:

• PaO2 will be obtained from ABG.
• FiO2 may be obtained from the setting on MV, CPAP, BIPAP, HFNO, or HFOV. If the patient is on RA, NC, FM, or NRB, Appendix Section 10.3 will be used for estimating FiO2 from oxygen delivery.

EXCLUSION CRITERIA:

1. Active malignancy requiring treatment within the last five years.
2. Any uncontrolled chronic respiratory disease, such as asthma or COPD.
3. Use of extracorporeal membrane oxygenation (ECMO) during the current hospitalization.
4. ALT or AST > 5 x Upper Limit of Normal (ULN).
5. Estimated Glomerular Filtration Rate (eGFR) < 30 ml/min.

6. Overt Disseminated Intravascular Coagulopathy (DIC) as evidenced by a total score of ≥ 5 on the following DIC score from International Society of Thrombosis & Hemostasis:

   • INR ≤ 1.3 (0 Points); 1.3- 1.7 (1 Point); > 1.7 (2 Points)
   • Fibrinogen > 100 mg/dL (0 Points); < 100 mg/dL (1 Point)
   • D-dimer < 400 ng/dL (0 Points); 400-4000 ng/mL (2 Points); >4,000 ng/ml (3 Points)
   • Platelets > 100,000/uL (0 Points); 50,000-100,000/uL (1 Point); < 50,000/uL (2 Points)
7. Pneumonia that is primarily attributable to a non-COVID-19 related process, including tuberculosis, mycoplasma, aspiration pneumonia or pneumonia that is exclusively bacterial, or originating from a diagnosed alternative virus (e.g., influenza).
8. DNR order, as in electing not to receive chest compressions, cardiac defibrillation, cardiac drugs, or intubation.
9. Endotracheal intubation duration > 48 hours.
10. Moribund-expected survival < 24 hours.
11. Severe metabolic disturbances on presentation (e.g., ketoacidosis, pH < 7.3)