Repair of acute respiratory distress syndrome in COVID-19 by stromal cells (REALIST-COVID Trial): A multicentre, randomised, controlled trial

Ellen A Gorman, Jennifer Rynne, Hannah J Gardiner, Anthony J Rostron, Jonathan Bannard-Smith, Andrew M Bentley, David Brealey, Christina Campbell, Gerard Curley, Mike Clarke, Ahilanadan Dushianthan, Phillip Hopkins, Colette Jackson, Kallirroi Kefela, Anna Krasnodembskaya, John G. Laffey, Cliona McDowell, Margaret McFarland, Jamie McFerran, Peter McGuiganGavin D Perkins, Jonathan Silversides, Jon Smythe, Jacqui Thompson, William S Tunnicliffe, Ingeborg DM Welters, Laura Amado-Rodríguez, Guillermo Albaiceta, Barry Williams, Manu Shankar-Hari, Daniel F. McAuley, Cecilia M. O'Kane

Research output: Contribution to journalArticlepeer-review


RATIONALE: Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in COVID-19-related Acute Respiratory Distress Syndrome (ARDS).

OBJECTIVES: We investigated safety and efficacy of ORBCEL-C (CD362-enriched, umbilical cord-derived MSCs) in COVID-related ARDS.

METHODS: 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).

MEASUREMENTS: 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.

MAIN RESULTS: 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 98.357.2], placebo 96.667.3). 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.

CONCLUSION: 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.

Original languageEnglish
Pages (from-to)256-269
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number3
Early online date08 May 2023
Publication statusPublished - 01 Aug 2023


  • Critical Care and Intensive Care Medicine
  • Pulmonary and Respiratory Medicine


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