Multiple Dosing of Mesenchymal Stromal Cells in Patients With ARDS (COVID-19)

Prior treatment

• Concurrent use of other investigational agents specifically for treatment of ARDS or inflammatory cytokines. (Note: Agents established to be efficacious and/or those used outside of formal trials are permitted as supportive data emerge)
• Other concurrent life-threatening disease (life expectancy \<6 months) or eligible for hospice care
• Concurrent diagnosis of diffuse alveolar hemorrhage

Other illness

• Active invasive malignant disease requiring chemotherapy/radiation
• Known history of HIV infection on active treatment
• History of any significant cardiac (myocardial infarction within 12 months of screening visit or unstable angina), chronic ongoing hepatic, or renal disease (grade 3 or higher); diagnosis of congestive heart failure with hypoxemia primarily due to decompensated heart failure; diagnosis of severe chronic obstructive pulmonary disease (COPD) or interstitial lung disease requiring supplemental oxygen at home

Lab values

• Known allergy to MSC components: fetal calf serum, human albumin or DMSO

Other

• Ventilator support of FiO2 \>0·8 or PEEP \>20 cm H2O and ongoing use of more than two vasopressors for 2 or more hours with any agent at doses shown below in the supine position.
  • Norepinephrine \>12 μg/min or 0.2 μg/kg per min
  • Phenylephrine \>150 μg/min or 3 μg/kg per min
  • Epinephrine \>10 ug/min or 0.2 μg/kg per min
  • Vasopressin \>0.04 units/min
• Known ineligibility for use of a ventilator for a minimum of 7 days, as judged by the institution's Triage Team
• Females who are pregnant or breastfeeding
• Current mean arterial pressure (MAP) \<60 mmHg while on 2 or more vasopressors at above doses for more than 2 hours
• Requiring continuous dialysis (unable to stop dialysis during study agent infusion)

• Age 18-80 years
• Meets 'Berlin Criteria' for diagnosis of moderate to severe ARDS for a minimum of 4 hours
• Less than 48 hours on a ventilator after meeting criteria for diagnosis of ARDS
• SARS-CoV-2 (proven by RT-PCR assay) with radiographic infiltrates
• PaO2/FiO2 \< 250
• Positive end-expiratory airway pressure (PEEP) \>5 cm H20
• Elevated C-reactive protein (above laboratory upper limit of normal)
• Meets organ function requirements, including left ventricular ejection fraction (LVEF) \>35% ( as defined below)
• Off other investigational agents directed against inflammatory cytokines 48 hours prior to enrollment; agents directed against the replication of SARS-CoV-2 \[e.g., Remdesivir\] are permitted
• Voluntary informed consent in person or virtually by the patient or patient surrogate considering the face to face limitations during the COVID-19 pandemic and, given the nature of the study population, which frequently requires mechanical ventilation with sedation, surrogate consent will likely occur in a substantial proportion of the study population (this will remain a valid consent until the patient is fully alert, and aware, and can provide a second consent to continue participation in the study).
• Adequate organ function is defined as:
  • Renal: Calculated estimated glomerular filtration rate \>30 mL/min/1.73 m2 (on chemistry panel)
  • Hepatic: Bilirubin \<3x upper limit of normal (ULN) and AST, ALT and alkaline phosphatase \<5x ULN
  • Cardiac: Absence of uncontrolled arrhythmia and LVEF \>35%