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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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cam.issuedOnline2021-11-23
dc.contributor.authorBellingan, G
dc.contributor.authorJacono, F
dc.contributor.authorBannard-Smith, J
dc.contributor.authorBrealey, D
dc.contributor.authorMeyer, N
dc.contributor.authorThickett, D
dc.contributor.authorYoung, D
dc.contributor.authorBentley, A
dc.contributor.authorMcVerry, BJ
dc.contributor.authorWunderink, RG
dc.contributor.authorDoerschug, KC
dc.contributor.authorSummers, C
dc.contributor.authorRojas, M
dc.contributor.authorTing, A
dc.contributor.authorJenkins, ED
dc.contributor.orcidBellingan, G [0000-0003-4193-4689]
dc.contributor.orcidTing, A [0000-0002-5058-9576]
dc.date.accessioned2022-01-10T12:46:37Z
dc.date.available2022-01-10T12:46:37Z
dc.date.issued2022-01
dc.date.submitted2021-08-17
dc.date.updated2022-01-10T12:46:36Z
dc.description.abstractPURPOSE: 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/FiO2 < 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.
dc.description.sponsorshipNational Institutes of Health, Innovate UK, and Athersys, Inc
dc.identifier.doi10.17863/CAM.79951
dc.identifier.eissn1432-1238
dc.identifier.issn0342-4642
dc.identifier.others00134-021-06570-4
dc.identifier.other6570
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332501
dc.languageen
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1007/s00134-021-06570-4
dc.subjectAcute respiratory distress syndrome (ARDS)
dc.subjectMultipotent adult progenitor cells (MAPC)
dc.subjectStem cells
dc.subjectAdult
dc.subjectDouble-Blind Method
dc.subjectHumans
dc.subjectIntensive Care Units
dc.subjectQuality of Life
dc.subjectRespiratory Distress Syndrome
dc.subjectStem Cells
dc.subjectTreatment Outcome
dc.titleSafety 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.
dc.typeArticle
dcterms.dateAccepted2021-10-28
prism.endingPage44
prism.issueIdentifier1
prism.publicationNameIntensive Care Med
prism.startingPage36
prism.volume48
pubs.funder-project-idNational Institute on Alcohol Abuse and Alcoholism (R42AA024003)
pubs.funder-project-idInnovate UK (102165)
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1007/s00134-021-06570-4

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