Extracellular Vesicle Infusion Treatment for COVID-19 Associated ARDS
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.
- Pneumonia, Viral
- Eligible Ages
- Between 18 Years and 85 Years
- Eligible Genders
- Accepts Healthy Volunteers
- 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 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. 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.
- 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 sequalae 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)
- Phase 2
- Study Type
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Multi-center, double-blinded, placebo-controlled, randomized controlled trial.
- Primary Purpose
- Triple (Participant, Care Provider, Investigator)
- Masking Description
|Normal saline 100 mL||
Experimental Dose 1
|Normal saline 90 mL and ExoFlo 10 mL, which is 800 Billion Extracellular Vesicles.||
Experimental Dose 2
|Normal saline 85 mL and ExoFlo 15 mL, which is 1.2 Trillion Extracellular Vesicles.||
- NCT ID
- Direct Biologics, LLC
EXIT COVID-19 is a FDA-approved, phase II double-blinded, placebo-controlled randomized controlled trial that enrolled 120 patients admitted with COVID-19 associated moderate-to-severe ARDS across up to 15 hospital sites in the United States.