Purpose

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.

Conditions

Eligibility

Eligible Ages
Between 18 Years and 85 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 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.

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 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)

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Multi-center, double-blinded, placebo-controlled, randomized controlled trial.
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)
Masking Description
Double-blinded

Arm Groups

ArmDescriptionAssigned Intervention
Placebo Comparator
Placebo
Normal saline 100 mL
  • Other: Intravenous normal saline
    Placebo
Experimental
Experimental Dose 1
Normal saline 90 mL and ExoFlo 10 mL, which is 800 Billion Extracellular Vesicles.
  • Biological: DB-001
    Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles
Experimental
Experimental Dose 2
Normal saline 85 mL and ExoFlo 15 mL, which is 1.2 Trillion Extracellular Vesicles.
  • Biological: DB-001
    Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles

Recruiting Locations

More Details

NCT ID
NCT04493242
Status
Completed
Sponsor
Direct Biologics, LLC

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.