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- Title
A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe ARDS From COVID-19.
- Authors
Bowdish, Michael E.; Barkauskas, Christina E.; Overbey, Jessica R.; Gottlieb, Robert L.; Osman, Keren; Duggal, Abhijit; Marks, Mary E.; Hupf, Jonathan; Fernandes, Eustace; Leshnower, Bradley G.; Golob, Jonathan L.; Iribarne, Alexander; Rassias, Athos J.; Moquete, Ellen G.; O’Sullivan, Karen; Chang, Helena L.; Williams, Judson B.; Parnia, Sam; Patel, Nirav C.; Desai, Nimesh D.
- Abstract
<bold>Rationale: </bold>There are limited therapeutic options for patients with COVID-19-related acute respiratory distress syndrome (ARDS) with inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents.<bold>Objectives: </bold>Evaluation of efficacy and safety of allogeneic mesenchymal cells in mechanically-ventilated patients with moderate or severe COVID-induced respiratory failure.<bold>Methods: </bold>Patients were randomized to two infusions of 2 million cells/kg or sham infusions, in addition to standard of care. We hypothesized that cell therapy would be superior to sham-control for the primary endpoint of 30-day mortality. The key secondary endpoint was ventilator-free survival within 60 days, accounting for deaths and withdrawals in a ranked analysis.<bold>Measurements and Main Results: </bold>At the third interim analysis, the Data and Safety Monitoring Board recommended that the trial halt enrollment as the pre-specified mortality reduction from 40% to 23% was unlikely to be achieved (n=222 out of planned 300). Thirty-day mortality was 37.5% (42/112) in cell recipients versus 42.7% (47/110) in control patients (RR 0.88;95% CI 0.64,1.21;p=0.43). There were no significant differences in days alive off ventilation within 60 days (median rank 117.3 [IQR:60.0,169.5] in cell patients and 102.0 [IQR:54.0,162.5] in controls; higher is better). Resolution or improvement of ARDS at 30-days was observed in 51/104 (49.0%) cell recipients and 46/106 (43.4%) of control patients (OR 1.36;95% CI 0.57, 3.21). There were no infusion-related toxicities and overall serious adverse events over 30 days were similar.<bold>Conclusions: </bold>Mesenchymal cells, while safe, did not improve 30-day survival or 60-day ventilator-free days in patients with moderate/severe COVID-related acute respiratory distress syndrome. Clinical trial registration available at www.<bold>Clinicaltrials: </bold>gov, ID:NCT04371393. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
- Subjects
STROMAL cells; ARTIFICIAL respiration; ADULT respiratory distress syndrome
- Publication
American Journal of Respiratory & Critical Care Medicine, 2023, Vol 207, Issue 3, p261
- ISSN
1073-449X
- Publication type
Article
- DOI
10.1164/rccm.202201-0157OC