Background Severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2)-induced acute respiratory distress syndrome (ARDS) causes high mortality. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have potentially relevant immune-modulatory properties, whose place in ARDS treatment is not established. This phase 2b trial was undertaken to assess the efficacy of UC-MSCs in patients with SARS–CoV-2-induced ARDS. Methods This multicentre, double-blind, randomized, placebo-controlled trial (STROMA–CoV-2) recruited adults (≥ 18 years) with SARS–CoV-2-induced early (< 96 h) mild-to-severe ARDS in 10 French centres. Patients were randomly assigned to receive three intravenous infusions of 10 6 UC-MSCs/kg or placebo (0.9% NaCl) over 5 days after recruitment. For the modified intention-to-treat population, the primary endpoint was the partial pressure of oxygen to fractional inspired oxygen (PaO 2 /FiO 2 )-ratio change between baseline (day (D) 0) and D7. Results Among the 107 patients screened for eligibility from April 6, 2020, to October 29, 2020, 45 were enrolled, randomized and analyzed. PaO 2 /FiO 2 changes between D0 and D7 did not differ significantly between the UC-MSCs and placebo groups (medians [IQR] 54.3 [− 15.5 to 93.3] vs 25.3 [− 33.3 to 104.6], respectively; ANCOVA estimated treatment effect 7.4, 95% CI − 44.7 to 59.7; P = 0.77). Six (28.6%) of the 21 UC-MSCs recipients and six of 24 (25%) placebo-group patients experienced serious adverse events, none of which were related to UC-MSCs treatment. Conclusions D0-to-D7 PaO 2 /FiO 2 changes for intravenous UC-MSCs-versus placebo-treated adults with SARS–CoV-2-induced ARDS did not differ significantly. Repeated UC-MSCs infusions were not associated with any serious adverse events during treatment or thereafter (until D28). Larger trials enrolling patients earlier during the course of their ARDS are needed to further assess UC-MSCs efficacy in this context. Trial registration : NCT04333368. Registered 01 April 2020, https://clinicaltrials.gov/ct2/history/NCT04333368 . Supplementary Information The online version contains supplementary material available at 10.1186/s13054-022-03930-4.
【저자키워드】 acute respiratory distress syndrome, severe acute respiratory syndrome coronavirus-2, Umbilical cord-derived mesenchymal stromal cells, Good-manufacturing practice, 【초록키워드】 Treatment, Efficacy, ARDS, Trial, oxygen, Randomized, placebo-controlled trial, Patient, Placebo, multicentre, recruitment, change, acute respiratory distress, Coronavirus-2, double-blind, intravenous, intravenous infusion, stromal cell, Serious Adverse Events, Serious Adverse Event, acute respiratory syndrome, supplementary material, 95% CI, placebo group, fractional inspired oxygen, syndrome, high mortality, eligibility, UC-MSCs, NaCl, ANCOVA, French, recipient, Randomly, modified intention-to-treat, Course, Result, enrolled, not differ, analyzed, significantly, recruited, screened, cause, assigned, receive, baseline, PaO, the primary endpoint, UC-MSC, 【제목키워드】 Randomized, multicenter, double-blind trial, COVID-19-associated ARDS,