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.
COVID-19
bone marrow mesenchymal stem cell
efficacy
extracellular vesicle
safety
Journal
Chest
ISSN: 1931-3543
Titre abrégé: Chest
Pays: United States
ID NLM: 0231335
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
22
02
2023
revised:
05
06
2023
accepted:
15
06
2023
pubmed:
26
6
2023
medline:
26
6
2023
entrez:
25
6
2023
Statut:
ppublish
Résumé
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. Do two doses of ExoFlo safely reduce mortality in COVID-19-associated moderate to severe ARDS compared with placebo? A prospective phase 2 multicenter double-anonymized 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. 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 The 15 mL dose of ExoFlo was found to be 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. ClinicalTrials.gov; No.: NCT04493242; URL: www. gov.
Sections du résumé
BACKGROUND
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
OBJECTIVE
Do two doses of ExoFlo safely reduce mortality in COVID-19-associated moderate to severe ARDS compared with placebo?
STUDY DESIGN AND METHODS
METHODS
A prospective phase 2 multicenter double-anonymized 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
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
CONCLUSIONS
The 15 mL dose of ExoFlo was found to be 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
BACKGROUND
ClinicalTrials.gov; No.: NCT04493242; URL: www.
CLINICALTRIALS
RESULTS
gov.
Identifiants
pubmed: 37356708
pii: S0012-3692(23)00926-1
doi: 10.1016/j.chest.2023.06.024
pmc: PMC10289818
pii:
doi:
Banques de données
ClinicalTrials.gov
['NCT04493242']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1444-1453Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. L. L. is CMO at Direct Biologics. J. T. R. is a PhD at Direct Biologics. S. Q. and V. S. are prior associate CMOs at Direct Biologics. None declared (S. S., D. J. P., T. I. M., B. P. W., J. J. W., M. A.).