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Safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (MUST-ARDS): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial
PURPOSE: Bone marrow-derived, allogeneic, multipotent adult progenitor cells demonstrated safety and efficacy in preclinical models of acute respiratory distress syndrome (ARDS). METHODS: This phase 1/2 trial evaluated the safety and tolerability of intravenous multipotent adult progenitor cells in...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608557/ https://www.ncbi.nlm.nih.gov/pubmed/34811567 http://dx.doi.org/10.1007/s00134-021-06570-4 |
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author | Bellingan, G. Jacono, F. Bannard-Smith, J. Brealey, D. Meyer, N. Thickett, D. Young, D. Bentley, A. McVerry, B. J. Wunderink, R. G. Doerschug, K. C. Summers, C. Rojas, M. Ting, A. Jenkins, E. D. |
author_facet | Bellingan, G. Jacono, F. Bannard-Smith, J. Brealey, D. Meyer, N. Thickett, D. Young, D. Bentley, A. McVerry, B. J. Wunderink, R. G. Doerschug, K. C. Summers, C. Rojas, M. Ting, A. Jenkins, E. D. |
author_sort | Bellingan, G. |
collection | PubMed |
description | PURPOSE: Bone marrow-derived, allogeneic, multipotent adult progenitor cells demonstrated safety and efficacy in preclinical models of acute respiratory distress syndrome (ARDS). METHODS: This phase 1/2 trial evaluated the safety and tolerability of intravenous multipotent adult progenitor cells in patients with moderate-to-severe ARDS in 12 UK and USA centres. Cohorts 1 and 2 were open-label, evaluating acute safety in three subjects receiving 300 or 900 million cells, respectively. Cohort 3 was a randomised, double-blind, placebo-controlled parallel trial infusing 900 million cells (n = 20) or placebo (n = 10) within 96 h of ARDS diagnosis. Primary outcomes were safety and tolerability. Secondary endpoints included clinical outcomes, quality of life (QoL) and plasma biomarkers. RESULTS: No allergic or serious adverse reactions were associated with cell therapy in any cohort. At baseline, the cohort 3 cell group had less severe hypoxia. For cohort 3, 28-day mortality was 25% for cell vs. 45% for placebo recipients. Median 28-day free from intensive care unit (ICU) and ventilator-free days in the cell vs. placebo group were 12.5 (IQR 0,18.5) vs. 4.5 (IQR 0,16.8) and 18.5 (IQR 0,22) vs. 6.5 (IQR 0,18.3), respectively. A prospectively defined severe ARDS subpopulation (PaO(2)/FiO(2) < 150 mmHg (20 kPa); n = 16) showed similar trends in mortality, ICU-free days and ventilator-free days favouring cell therapy. Cell recipients showed greater recovery of QoL through Day 365. CONCLUSIONS: Multipotent adult progenitor cells were safe and well tolerated in ARDS. The clinical outcomes warrant larger trials to evaluate the therapeutic efficacy and optimal patient population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00134-021-06570-4. |
format | Online Article Text |
id | pubmed-8608557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-86085572021-11-23 Safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (MUST-ARDS): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial Bellingan, G. Jacono, F. Bannard-Smith, J. Brealey, D. Meyer, N. Thickett, D. Young, D. Bentley, A. McVerry, B. J. Wunderink, R. G. Doerschug, K. C. Summers, C. Rojas, M. Ting, A. Jenkins, E. D. Intensive Care Med Original PURPOSE: Bone marrow-derived, allogeneic, multipotent adult progenitor cells demonstrated safety and efficacy in preclinical models of acute respiratory distress syndrome (ARDS). METHODS: This phase 1/2 trial evaluated the safety and tolerability of intravenous multipotent adult progenitor cells in patients with moderate-to-severe ARDS in 12 UK and USA centres. Cohorts 1 and 2 were open-label, evaluating acute safety in three subjects receiving 300 or 900 million cells, respectively. Cohort 3 was a randomised, double-blind, placebo-controlled parallel trial infusing 900 million cells (n = 20) or placebo (n = 10) within 96 h of ARDS diagnosis. Primary outcomes were safety and tolerability. Secondary endpoints included clinical outcomes, quality of life (QoL) and plasma biomarkers. RESULTS: No allergic or serious adverse reactions were associated with cell therapy in any cohort. At baseline, the cohort 3 cell group had less severe hypoxia. For cohort 3, 28-day mortality was 25% for cell vs. 45% for placebo recipients. Median 28-day free from intensive care unit (ICU) and ventilator-free days in the cell vs. placebo group were 12.5 (IQR 0,18.5) vs. 4.5 (IQR 0,16.8) and 18.5 (IQR 0,22) vs. 6.5 (IQR 0,18.3), respectively. A prospectively defined severe ARDS subpopulation (PaO(2)/FiO(2) < 150 mmHg (20 kPa); n = 16) showed similar trends in mortality, ICU-free days and ventilator-free days favouring cell therapy. Cell recipients showed greater recovery of QoL through Day 365. CONCLUSIONS: Multipotent adult progenitor cells were safe and well tolerated in ARDS. The clinical outcomes warrant larger trials to evaluate the therapeutic efficacy and optimal patient population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00134-021-06570-4. Springer Berlin Heidelberg 2021-11-23 2022 /pmc/articles/PMC8608557/ /pubmed/34811567 http://dx.doi.org/10.1007/s00134-021-06570-4 Text en © Crown 2021 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Original Bellingan, G. Jacono, F. Bannard-Smith, J. Brealey, D. Meyer, N. Thickett, D. Young, D. Bentley, A. McVerry, B. J. Wunderink, R. G. Doerschug, K. C. Summers, C. Rojas, M. Ting, A. Jenkins, E. D. Safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (MUST-ARDS): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial |
title | Safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (MUST-ARDS): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial |
title_full | Safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (MUST-ARDS): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial |
title_fullStr | Safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (MUST-ARDS): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial |
title_full_unstemmed | Safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (MUST-ARDS): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial |
title_short | Safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (MUST-ARDS): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial |
title_sort | safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (must-ards): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial |
topic | Original |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608557/ https://www.ncbi.nlm.nih.gov/pubmed/34811567 http://dx.doi.org/10.1007/s00134-021-06570-4 |
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