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

• Published in: Intensive care medicine 2022-01, Vol.48 (1), p.36-44
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Acute respiratory distress syndrome; Adult; Analysis; Anesthesiology; Biomarkers; Biotechnology industry; Bone marrow; Cell therapy; Cells (biology); Clinical outcomes; Clinical trials; Complications and side effects; Critical Care Medicine; Double-Blind Method; Double-blind studies; Emergency Medicine; Humans; Hypersensitivity; Hypoxia; Intensive; Intensive care; Intensive Care Units; Intravenous administration; Medical colleges; Medicine; Medicine & Public Health; Mortality; NCT; NCT02611609; Original; Pain Medicine; Patients; Pediatrics; Placebos; Pneumology/Respiratory System; Product development; Progenitor cells; Quality of Life; Respiratory distress syndrome; Respiratory Distress Syndrome - therapy; Safety; Stem Cells; Treatment Outcome; Ventilators
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s00134-021-06570-4

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