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

G. Bellingan; F. Jacono; J. Bannard-Smith; D. Brealey; N. Meyer; D. Thickett; D. Young; A. Bentley; B. J. McVerry; R. G. Wunderink; K. C. Doerschug; C. Summers; M. Rojas; A. Ting; E. D. Jenkins

doi:10.1007/s00134-021-06570-4

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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

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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

G. Bellingan, F. Jacono, J. Bannard-Smith, D. Brealey, N. Meyer, D. Thickett, D. Young, A. Bentley, B. J. McVerry, R. G. Wunderink, …

Intensive care medicine, Vol.48(1), pp.36-44

01/01/2022

DOI: 10.1007/s00134-021-06570-4

PMCID: PMC8608557

PMID: 34811567

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Abstract

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 (PaO2/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.

Critical Care Medicine

General & Internal Medicine

Life Sciences & Biomedicine

Science & Technology

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Title: Subtitle: 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
Creators: G. Bellingan - University College London
F. Jacono - Case Western Reserve University
J. Bannard-Smith - Manchester University NHS Foundation Trust
D. Brealey - University College London
N. Meyer - University of Pennsylvania
D. Thickett - University Hospitals Birmingham NHS Foundation Trust
D. Young - John Radcliffe Hospital
A. Bentley - Critical Care, South Manchester University Hospital Trust, Manchester, UK
B. J. McVerry - The Ohio State University
R. G. Wunderink - Northwestern University
K. C. Doerschug - University of Iowa
C. Summers - University of Cambridge
M. Rojas - The Ohio State University
A. Ting - Athersys (United States)
E. D. Jenkins - Athersys (United States)
Resource Type: Journal article
Publication Details: Intensive care medicine, Vol.48(1), pp.36-44
DOI: 10.1007/s00134-021-06570-4
PMID: 34811567
PMCID: PMC8608557
NLM abbreviation: Intensive Care Med
ISSN: 0342-4642
eISSN: 1432-1238
Publisher: Springer Nature
Number of pages: 9
Grant note: National Institutes of Health, Innovate UK; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Athersys, Inc.
Language: English
Date published: 01/01/2022
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
Record Identifier: 9984360146102771

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