Gorman, Ellen A, Rynne, Jennifer, Gardiner, Hannah J, Rostron, Anthony J, Bannard-Smith, Jonathan, Bentley, Andrew M, Brealey, David, Campbell, Christina, Curley, Gerard, Clarke, Mike et al (show 22 more authors)
(2023)
Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial): A Multicentre, Randomised, Controlled Trial.
American journal of respiratory and critical care medicine, 208 (3).
pp. 256-269.
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Abstract
<h4>Rationale</h4>Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in COVID-19-related Acute Respiratory Distress Syndrome (ARDS).<h4>Objectives</h4>We investigated safety and efficacy of ORBCEL-C (CD362-enriched, umbilical cord-derived MSCs) in COVID-related ARDS.<h4>Methods</h4>This multicentre, randomised, double-blind, allocation concealed, placebo-controlled trial (NCT03042143) randomised patients with moderate-to-severe COVID-related ARDS to receive ORBCEL-C (400million cells) or placebo (Plasma-Lyte148).<h4>Measurements</h4>The primary safety and efficacy outcomes were incidence of serious adverse events and oxygenation index at day 7 respectively. Secondary outcomes included respiratory compliance, driving pressure, PaO2/FiO2 ratio and SOFA score. Clinical outcomes relating to duration of ventilation, length of intensive care unit and hospital stays, and mortality were collected. Long-term follow up included diagnosis of interstitial lung disease at 1 year, and significant medical events and mortality at 2 years. Transcriptomic analysis was performed on whole blood at day 0, 4 and 7.<h4>Main results</h4>60 participants were recruited (final analysis n=30 ORBCEL-C, n=29 placebo: 1 in placebo group withdrew consent). 6 serious adverse events occurred in the ORBCEL-C and 3 in the placebo group, RR 2.9(0.6-13.2)p=0.25. Day 7 mean[SD] oxygenation index did not differ (ORBCEL-C 98.357.2], placebo 96.667.3). There were no differences in secondary surrogate outcomes, nor mortality at day 28, day 90, 1 or 2 years. There was no difference in prevalence of interstitial lung disease at 1year nor significant medical events up to 2 years. ORBCEL-C modulated the peripheral blood transcriptome.<h4>Conclusion</h4>ORBCEL-C MSCs were safe in moderate-to-severe COVID-related ARDS, but did not improve surrogates of pulmonary organ dysfunction. Clinical trial registration available at www.<h4>Clinicaltrials</h4>gov, ID: NCT03042143. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | acute respiratory distress syndrome, coronavirus disease, mesenchymal stromal cells, clinical trial |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 29 Jun 2023 09:54 |
| Last Modified: | 16 Sep 2023 08:53 |
| DOI: | 10.1164/rccm.202302-0297oc |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3171363 |
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