Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicle Infusion for the Treatment of Respiratory Failure From COVID-19: A Randomized, Placebo-Controlled Dosing Clinical Trial.
california; pjsmc; covenant; texas; covid-19
BACKGROUND: Bone marrow mesenchymal stem cell (BM-MSC)-derived extracellular vesicles, ExoFlo, convey the immunomodulatory and regenerative properties of intact BM-MSCs. This study aimed to determine the safety and efficacy of ExoFlo as treatment for moderate to severe ARDS in patients with severe COVID-19.
RESEARCH QUESTION: Do two doses of ExoFlo safely reduce mortality in COVID-19-associated moderate to severe ARDS compared with placebo?
STUDY DESIGN AND METHODS: A prospective phase II, multicenter, double-blind, randomized, placebo-controlled dosing trial was conducted at five sites across the United States with infusions of placebo, 10 mL of ExoFlo, or 15 mL of ExoFlo on days 1 and 4. Patients (N = 102) with COVID-19-associated moderate to severe ARDS were enrolled and randomized to treatment. Adverse events were documented throughout the study. The primary outcome measure was all-cause 60-day mortality rate. Secondary outcomes included time to death (overall mortality); the incidence of treatment-emergent serious adverse events; proportion of discharged patients at 7, 30, and 60 days; time to hospital discharge; and ventilation-free days.
RESULTS: No treatment-related adverse events were reported. Mortality (60-day) in the intention-to-treat population was reduced with 15 mL ExoFlo mixed with 85 mL normal saline (ExoFlo-15) compared with placebo (not significant, χ
INTERPRETATION: The 15 mL dose of ExoFlo is safe in patients with severe or critical COVID-19-associated respiratory failure. In participants aged 18 to 65 years, the risk reduction in 60-day mortality was further improved from subjects of all ages in the intention-to-treat population after two doses of 15 mL of ExoFlo compared with placebo.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04493242; URL: www.
Lightner, Amy L; Sengupta, Vikram; Qian, Sascha; Ransom, John T; Suzuki, Sam; Park, David J; Melson, Timothy I; Williams, Brian P; Walsh, James J; and Awili, Mustafa, "Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicle Infusion for the Treatment of Respiratory Failure From COVID-19: A Randomized, Placebo-Controlled Dosing Clinical Trial." (2023). Articles, Abstracts, and Reports. 7701.