A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome from COVID-19

Michael E. Bowdish, Christina E. Barkauskas, Jessica R. Overbey, Robert L. Gottlieb, Keren Osman, Abhijit Duggal, Mary E. Marks, Jonathan Hupf, Eustace Fernandes, Bradley G. Leshnower, Jonathan L. Golob, Alexander Iribarne, Athos J. Rassias, Ellen G. Moquete, Karen O'Sullivan, Helena L. Chang, Judson B. Williams, Sam Parnia, Nirav C. Patel, Nimesh D. DesaiAndrew M. Vekstein, Beth A. Hollister, Tammie Possemato, Christian Romero, Peter C. Hou, Elizabeth Burke, Jack Hayes, Fred Grossman, Silviu Itescu, Marc Gillinov, Francis D. Pagani, Patrick T. O'Gara, Michael J. Mack, Peter K. Smith, Emilia Bagiella, Alan J. Moskowitz, Annetine C. Gelijns

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Rationale: There are limited therapeutic options for patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome with inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents. Objectives: Evaluation of efficacy and safety of allogeneic mesenchymal cells in mechanically-ventilated patients with moderate or severe COVID-19-induced respiratory failure. Methods: Patients were randomized to two infusions of 2 million cells/kg or sham infusions, in addition to the 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. Measurements and Main Results: At the third interim analysis, the data and safety monitoring board recommended that the trial halt enrollment as the prespecified 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 (relative risk [RR], 0.88; 95% confidence interval, 0.64-1.21; P= 0.43). There were no significant differences in days alive off ventilation within 60 days (median rank, 117.3 [interquartile range, 60.0-169.5] in cell patients and 102.0 [interquartile range, 54.0-162.5] in control subjects; higher is better). Resolution or improvement of acute respiratory distress syndrome at 30 days was observed in 51/104 (49.0%) cell recipients and 46/106 (43.4%) control patients (odds ratio, 1.36; 95% confidence interval, 0.57-3.21). There were no infusion-related toxicities and overall serious adverse events over 30 days were similar. Conclusions: Mesenchymal cells, while safe, did not improve 30-day survival or 60-day ventilator-free days in patients with moderate and/or severe COVID-19-related acute respiratory distress syndrome.

Original languageEnglish
Pages (from-to)261-270
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume207
Issue number3
DOIs
StatePublished - 1 Feb 2023

Keywords

  • SARS-CoV-2
  • clinical trial
  • mechanical ventilation
  • stem cells
  • survival

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