Details

Autor(en) / Beteiligte

• 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
• Dushianthan, Ahilanadan
• Hopkins, Phillip
• Jackson, Colette
• Kefela, Kallirroi
• Krasnodembskaya, Anna
• Laffey, John G
• McDowell, Cliona
• McFarland, Margaret
• McFerran, Jamie
• McGuigan, Peter
• Perkins, Gavin D
• Silversides, Jonathan
• Smythe, Jon
• Thompson, Jacqui
• Tunnicliffe, William S
• Welters, Ingeborg D M
• Amado-Rodríguez, Laura
• Albaiceta, Guillermo
• Williams, Barry
• Shankar-Hari, Manu
• McAuley, Daniel F
• O'Kane, Cecilia M

Titel

Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial): A Multicenter, Randomized, Controlled Clinical Trial

Ist Teil von

• American journal of respiratory and critical care medicine, 2023-08, Vol.208 (3), p.256-269

Ort / Verlag

United States: American Thoracic Society

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in coronavirus disease (COVID-19)-related acute respiratory distress syndrome (ARDS). We investigated the safety and efficacy of ORBCEL-C (CD362 [cluster of differentiation 362]-enriched, umbilical cord-derived MSCs) in COVID-19-related ARDS. In this multicenter, randomized, double-blind, allocation-concealed, placebo-controlled trial (NCT03042143), 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, Pa :Fi 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. Sixty participants were recruited (final analysis:  = 30 received ORBCEL-C,  = 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];  = 0.25). Day 7 mean (SD) oxygenation index did not differ (ORBCEL-C, 98.3 [57.2] cm H O/kPa; placebo, 96.6 [67.3] cm H O/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. ORBCEL-C MSCs were safe in subjects with moderate to severe COVID-19-related ARDS but did not improve surrogates of pulmonary organ dysfunction.