EXIT-COVID19: Extracellular Vesicle Infusion Treatment for COVID-19 Associated ARDS
Study Details
Study Description
Brief 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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
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
|
Outcome Measures
Primary Outcome Measures
- 7 Day Change in Partial Pressure of Arterial Oxygen to Fraction of Inspired Oxygen Ratio [61 days]
Efficacy Endpoint; PaO2/FiO2 ratio
Secondary Outcome Measures
- Time to Recovery [61 days]
The number of days from the first study treatment until return of oxygenation saturation (SpO2) ≥ 93% on room air (or PaO2/FiO2 ≥ 300 mmHg). If patient has chronic lung disease, recovery is defined as pre-COVID-19 SpO2 and O2 support.
- Incidence of Serious Adverse Events (SAE) [61 days]
Safety Endpoint
- Number of Patients with All-cause Mortality [61 days]
Efficacy Endpoint
Other Outcome Measures
- Serum Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Ribonucleic Acid (RNA) Level [Days = 1, 4, 7, 10, 15, 29 *Labs are not drawn after hospitalization.]
Viremia
- CRP, D-dimer, Ferritin, IL-6, TNF-α [Days = 1, 4, 7, 10, 15, 29 *Labs are not drawn after hospitalization]
Acute Phase Reactants
- Absolute Neutrophil Count (ANC), CD3+, CD4+, and CD8+ T Cells, NK Cells [Days = 1, 4, 7, 10, 15, 29 *Labs are not drawn after hospitalization.]
Immune Cell Counts
- Sequential Organ Failure Assessment (SOFA) [Days = 1, 15, 29 *Labs are only drawn if patient is still hospitalized.]
Mortality Prediction Score Ranging from 0 to 24 with Higher SOFA Score Correlating with Higher Mortality
- EQ-5D-5L Description Part Only, Which Includes 5 Dimensions of Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety Depression) [Days = 15, 29, and 61 *Only Assessed for Outpatients]
Standardized Quality of Life Metric Where Each Dimension Is Assessed via 5 Levels; 5 Levels for Each Digit is Combined into a 5 Digit Descriptor.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Provision of signed and dated informed consent form (either by the individual or by the individual's healthcare proxy).
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Stated willingness to comply with all study procedures and availability for the duration of the study
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Male or female, aged 18-85.
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COVID-19 positive as defined by positive RT-PCR SARS-CoV-2.
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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.
-
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.
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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:
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Vulnerable populations such as pregnant patients, children, individuals with severe physical or mental disabilities who cannot provide meaningful consent.
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Active malignancy requiring treatment within the last five years.
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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.
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Active tuberculosis or cystic fibrosis.
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Severe chronic respiratory disease including chronic obstructive pulmonary disease or pulmonary fibrosis requiring home oxygen > 5L/min.
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Use of extracorporeal membrane oxygenation (ECMO) during the current hospitalization.
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Pre-existing pulmonary hypertension.
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Severe pre-existing hepatic impairment (presence of cirrhosis, liver function tests (LFTs) ≥ 6x baseline, INR ≥ 2.0).
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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)
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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).
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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).
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Patients who are not full code.
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Endotracheal intubation duration ≤ 24 hours.
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Moribund-expected survival < 24 hours.
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Severe metabolic disturbances on presentation (e.g., ketoacidosis, pH < 7.3)
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Helen Keller Hospital | Sheffield | Alabama | United States | 35660 |
2 | St. Joseph Hospital Heritage | Fullerton | California | United States | 92835 |
3 | Donald Guthrie Foundation/ Robert Packer Hospital | Sayre | Pennsylvania | United States | 18810 |
4 | Covenant Health | Lubbock | Texas | United States | 79410 |
5 | PRX Research | Mesquite | Texas | United States | 75149 |
Sponsors and Collaborators
- Direct Biologics, LLC
Investigators
- Study Chair: Vikram Sengupta, MD, Chief Medical Officer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- DB-EF-PHASEII-001