Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles as Early Goal Directed Therapy for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial

• Status: Not yet recruiting
• Trial end date: 2023-01-03
• Target enrollment: 0
• Participant gender: All

Summary

Extracellular Vesicle Infusion as Early Goal Directed Therapy for COVID-19 related ARDS (EXTINGuish COVID-19) is a multicenter, double-blinded, placebo-controlled, randomized clinical trial to evaluate the efficacy of ExoFlo in treating moderate to severe ARDS caused by COVID-19.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Direct Biologics, LLC

Criteria

Inclusion Criteria:

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Admitted to hospital with symptoms suggestive of COVID-19 infection.

Subject (or legally authorized representative) provides informed consent prior to the initiation of any study procedures.

Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.

Male or nonpregnant female aged 18-85 of age at time of enrollment.

Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR as documented by either of the following:

PCR positive in sample collected < 72 hours prior to randomization; OR

PCR positive in sample collected ≥ 72 hours prior to randomization, documented inability to obtain a repeat sample (e.g. due to lack of testing supplies, limited testing capacity, results taking > 24 hours, etc.). AND progressive disease suggestive of ongoing SARS-CoV-2 infection.

Presence of moderate-to-severe ARDS as defined by Berlin criteria (i-iv).

Onset within one week of known clinical insult or new or worsening respiratory symptoms

Bilateral opacities consistent with pulmonary edema on chest imaging

PaO2/FiO2 (P/F ratio) ≤ 200 mm Hg

Minimum 5 cm H2O PEEP on mechanical ventilation or acceptable equivalent*.

Must not be fully explained by cardiac failure or fluid overload.

*Minimum 5 cm H2O PEEP on BiPAP, minimum 5 cm H2O CPAP, or minimum 30 L/min on HFNC.

Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from time of screening through Day 29.

Exclusion Criteria:

• Active malignancy requiring treatment within the last five years.

Major physical trauma in the last 5 days, including accidents, assaults, and falls.

Any chronic respiratory disease, such as tuberculosis, cystic fibrosis, or pulmonary hypertension.

Use of extracorporeal membrane oxygenation (ECMO) during the current hospitalization.

ALT or AST > 5 x Upper Limit of Normal (ULN)

Estimated Glomerular Filtration Rate (eGFR) < 30 ml/min

Overt Disseminated Intravascular Coagulopathy (DIC) as evidenced by a total score of ≥ 5 on the following DIC score from International Society of Thrombosis & Hemostasis:

INR ≤ 1.3 (0 Points); 1.3- 1.7 (1 Point); > 1.7 (2 Points)

Fibrinogen > 100 mg/dL (0 Points); < 100 mg/dL (1 Point)

D-dimer < 400 ng/dL (0 Points); 400-4000 ng/mL (2 Points); >4,000 ng/ml (3 Points)

Platelets > 100,000/uL (0 Points); 50,000-100,000/uL (1 Point); < 50,000/uL (2 Points)

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).

DNR order, as in electing not to receive chest compressions, cardiac defibrillation, cardiac drugs, or intubation.

Endotracheal intubation duration > 48 hours.

Moribund-expected survival < 24 hours.

Severe metabolic disturbances on presentation (e.g., ketoacidosis, pH < 7.3)