Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles as Early Goal Directed Therapy for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial
Eligibility
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Inclusion Criteria
To be eligible to participate in this study, a patient must meet all of the following criteria:
Admitted to hospital with symptoms suggestive of COVID-19 infection.
Subject (or legally authorized representative) provides informed consent prior to the
initiation of any study procedures.
Subject (or legally authorized representative) understands and agrees to comply with
planned study procedures.
Male or nonpregnant female aged 18-85 of age at time of enrollment.
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.
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
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.
5.2 Exclusion Criteria
Any individual who meets any of the following criteria will be excluded from participation in this
study:
Active malignancy requiring treatment within the last five years.
Any uncontrolled chronic respiratory disease, such as asthma or COPD.
Use of extracorporeal membrane oxygenation (ECMO) during the current hospitalization.
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)
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).