Mesenchymal Stromal Cells for ARDS (COVID positive and COVID negative)

Prior clinical trials have established the safety, but not the therapeutic efficacy of bone marrow-derived mesenchymal stromal cells (MSCs) in patients with acute respiratory distress syndrome (ARDS). To assess whether an intravenous infusion of MSCs in patients with ARDS would lead to a reduction in the severity of acute respiratory failure from ARDS as measured by the oxygenation index, we carried out a prospective, double-blind, multi-center randomized phase 2b clinical trial of one dose of intravenous MSCs (10 x 10⁶/kg/predicted body weight) versus placebo (1:1 randomization) in 120 ventilated patients with ARDS (PaO₂/FiO₂ < 250 mmHg with positive end-expiratory pressure [PEEP] ≥ 5 mm Hg). The primary endpoint was a change in oxygenation index (OI) from baseline for 36 hours, based on measurements every 6 hours, and plasma samples were obtained for biological assays.  From January 2020 to December 2022, a total of 120 patients were enrolled in seven sites nationwide. Due to the COVID-19 pandemic, the majority of enrolled patients (101/120, 84%) had COVID-19 associated ARDS subgroup, with a significant imbalance in treatment vs. control assignment for patients with non-COVID ARDS. The current clinical trial showed that there were no differences in serious adverse events (SAE) including deaths and non-serious adverse events (AE) occurrence in all enrolled patients and the patients with COVID-19. None of the AE/SAEs were considered to be related to the study product and study procedures.  This trial indicated that there was no difference in the changes in oxygenation index over 36 hours in those treated with the MSCs versus placebo, and there were no differences in mortality at 28 or 60 days after study product infusion. In conclusion, the results of this phase 2b trial showed no safety issues with the administration of a high dose of MSCs to COVID-19 ARDS patients, but there was no evidence of clinical benefit. Now that the pandemic has waned, future studies of MSCs for the treatment of ARDS should focus on more classical forms of ARDS.