Browse by author
Lookup NU author(s): Dr Anthony RostronORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
Copyright © 2023 by the American Thoracic Society. Rationale: Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in coronavirus disease (COVID-19)–related acute respiratory distress syndrome (ARDS). Objectives: We investigated the safety and efficacy of ORBCEL-C (CD362 [cluster of differentiation 362]–enriched, umbilical cord–derived MSCs) in COVID-19–related ARDS. Methods: In this multicenter, randomized, double-blind, allocation-concealed, placebo-controlled trial (NCT 03042143), patients with moderate to severe COVID-19–related ARDS were randomized to receive ORBCEL-C (400 million cells) or placebo (Plasma-Lyte 148). The primary safety and efficacy outcomes were the incidence of serious adverse events and oxygenation index at Day 7, respectively. Secondary outcomes included respiratory compliance, driving pressure, PaO2:FIO2 ratio, and Sequential Organ Failure Assessment score. Clinical outcomes relating to duration of ventilation, lengths of ICU 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 Days 0, 4, and 7. Measurements and Main Results: Sixty participants were recruited (final analysis: n = 30 received ORBCEL-C, n = 29 received placebo; 1 participant in the placebo group withdrew consent). Six serious adverse events occurred in the ORBCEL-C group and three in the placebo group (risk ratio, 2.9 [95% confidence interval, 0.6–13.2]; P = 0.25). Day 7 mean (SD) oxygenation index did not differ (ORBCEL-C, 98.3 [57.2] cm H2O/kPa; placebo, 96.6 [67.3] cm H2O/kPa). There were no differences in secondary surrogate outcomes or in mortality at Day 28, Day 90, 1 year, or 2 years. There was no difference in the prevalence of interstitial lung disease at 1 year or significant medical events up to 2 years. ORBCEL-C modulated the peripheral blood transcriptome. Conclusion: ORBCEL-C MSCs were safe in subjects with moderate to severe COVID-19–related ARDS but did not improve surrogates of pulmonary organ dysfunction.
Author(s): Gorman EA, Rynne J, Gardiner HJ, Rostron AJ, Bannard-Smith J, Bentley AM, Brealey D, Campbell C, Curley G, Clarke M, Dushianthan A, Hopkins P, Jackson C, Kefela K, Krasnodembskaya A, Laffey JG, McDowell C, McFarland M, McFerran J, McGuigan P, Perkins GD, Silversides J, Smythe J, Thompson J, Tunnicliffe WS, Welters IDM, Amado-Rodriguez L, Albaiceta G, Williams B, Shankar-Hari M, McAuley DF, O'Kane CM
Publication type: Article
Publication status: Published
Journal: American Journal of Respiratory and Critical Care Medicine
Year: 2023
Volume: 208
Issue: 3
Pages: 256-269
Print publication date: 01/08/2023
Online publication date: 08/05/2023
Acceptance date: 05/03/2023
Date deposited: 29/08/2024
ISSN (print): 1073-449X
ISSN (electronic): 1535-4970
Publisher: American Thoracic Society
URL: https://doi.org/10.1164/rccm.202302-0297OC
DOI: 10.1164/rccm.202302-0297OC
Data Access Statement: Data will be available to researchers on request subject to sponsor approval.
PubMed id: 37154608
Altmetrics provided by Altmetric
