| Autor: |
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, Desai, Andrew 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 |
| Rok vydání: |
2022 |
| Zdroj: |
American journal of respiratory and critical care medicine. |
| ISSN: |
1535-4970 |
| Popis: |
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.Evaluation of efficacy and safety of allogeneic mesenchymal cells in mechanically-ventilated patients with moderate or severe COVID-induced respiratory failure.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.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.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.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/). |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
