Extracellular Vesicle Infusion Treatment for COVID-19 Associated ARDS
Condition: COVID-19; ARDS
MeSH terms: COVID-19
Intervention: ExoFlo; Intravenous normal saline
Intervention description: Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Multi-center, double-blinded, placebo-controlled, randomized controlled trial.
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Double-blinded
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: COVID-19; ARDS; Extracellular Vesicles; Exosome

Summary:

      To evaluate the safety and efficacy of intravenous administration of bone marrow derived
      extracellular vesicles, ExoFlo, versus placebo as treatment for moderate-to-severe Acute
      Respiratory Distress Syndrome (ARDS) in patients with severe COVID-19.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of signed and dated informed consent form (either by the individual or by
             the individual's healthcare proxy).

          2. Stated willingness to comply with all study procedures and availability for the
             duration of the study

          3. Male or female, aged 18-85.

          4. COVID-19 positive as defined by positive Reverse Transcriptase Polymerase Chain
             Reaction (RT-PCR) SARS-CoV-2.

          5. Moderate to severe ARDS as defined by modified Berlin definition, * which includes
             timing within 1 week of known clinical insult or new or worsening respiratory
             symptoms; bilateral opacities not fully explained by effusions, or lung collapse;
             respiratory failure not fully explained by cardiac failure or fluid overload;
             PaO2/FiO2 ≤ 200 mm Hg.

             *Modified Berlin definition used in this study is the full Berlin definition, albeit
             without the PEEP specification, which implies mechanical ventilation.

          6. Hypoxia requiring noninvasive oxygen support such as Nasal Cannula (NC), Nonrebreather
             (NRB), Bilevel Positive Airway Pressure (BIPAP), Continuous Positive Airway Pressure
             (CPAP), high flow nasal cannula oxygen (HFNC O2) or mechanical ventilation (MV)
             despite initiating standard of care.

          7. If the candidate is either a male or female of reproductive potential, he or she must
             agree to use of double barrier method of highly effective birth control contraception
             such as condoms with oral contraceptive pill or choose to remain abstinent if already
             practicing abstinence during the screening period. The required duration of usage of
             double barrier method OR maintenance of abstinence must include the time from the
             beginning of the screening period until 90 days following the last dose of the study
             treatment.

        Exclusion Criteria:

          1. Vulnerable populations such as pregnant patients, children, individuals with severe
             physical or mental disabilities who cannot provide meaningful consent.

          2. Active malignancy requiring treatment within the last five years.

          3. Major physical trauma in the last 5 days, including motor vehicle accidents, assaults,
             mechanical falls with sequelae of significant bleeding or craniofacial bruising, and
             surgeries.

          4. Active tuberculosis or cystic fibrosis.

          5. Severe chronic respiratory disease including chronic obstructive pulmonary disease or
             pulmonary fibrosis requiring home oxygen > 5L/min.

          6. Use of extracorporeal membrane oxygenation (ECMO) during the current hospitalization.

          7. Pre-existing pulmonary hypertension.

          8. Severe pre-existing hepatic impairment (presence of cirrhosis, liver function tests
             (LFTs) ≥ 6x baseline, INR ≥ 2.0).

          9. Pre-existing Chronic Kidney Disease (CKD) stage IIIb or End Stage Renal Disease (ESRD)
             prior to onset of COVID-19 (stage I, II, and IIIa are acceptable)

         10. Irreversible coagulopathy (e.g., frequently occluded vascular access despite
             anticoagulation, precipitous platelet drops concurrent with end-organ damage
             suggesting consumptive process) or irreversible bleeding disorder (e.g., frequent
             bleeding from vascular access, endotracheal tubes, and foley).

         11. Pneumonia clearly attributable to a non-COVID-19 related process, including aspiration
             pneumonia or pneumonia that is exclusively bacterial, or originating from a diagnosed
             alternative virus (e.g., influenza).

         12. Patients who are not full code.

         13. Endotracheal intubation duration ≤ 24 hours.

         14. Moribund-expected survival < 24 hours.

         15. Severe metabolic disturbances on presentation (e.g., ketoacidosis, pH < 7.3)