Treatment with Allogeneic Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome: A Double-Blind, Placebo-controlled, Multicenter Phase 2b Clinical Trial (STAT).

rationalePrior clinical trials established the safety but not the efficacy of bone marrow-derived mesenchymal stromal cells (MSCs) in acute respiratory distress syndrome (ARDS).

objectivesTo compare the efficacy of bone marrow-derived MSCs versus placebo in ARDS.

methodsProspective, double-blind, multicenter, randomized phase 2b clinical trial of one dose of intravenous MSCs (10 × 106/kg predicted body weight) versus placebo in 120 ventilated patients with ARDS (PaO2/FiO2 ratio <250 mm Hg). The primary endpoint was change in oxygenation index during the 36 hours after baseline. MEASUREMENTS AND MAIN

resultsEnrollment began in January 2020. Because of the coronavirus disease (COVID-19) pandemic, ARDS developed from COVID-19 in the majority of subjects (101 of 120; 84%). There were no significant baseline differences in severity of illness between patients treated with MSCs and those who received placebo in the entire cohort of 120 patients or in the 101 patients with COVID-19 ARDS. There were no differences in the primary endpoint of change in oxygenation index from baseline during the 36 hours after study product administration for the entire cohort or the COVID-19 subgroup, nor were there significant differences in mortality at 14, 28, 60, or 180 days. Plasma protein biomarker and gene expression analyses identified subgroups of patients with differential treatment responses in terms of clinical outcomes.

conclusionsThis phase 2b clinical trial identified no physiologic or clinical benefit from a single dose of MSCs in patients with ARDS, including those with COVID-19 ARDS. In future trials, baseline plasma biological markers may help identify patients who are more likely to benefit from MSC therapy.Clinical trial registered with www. CLINICALTRIALS: gov (NCT03818854).