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

Autor:	Gorman EA; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom., Rynne J; Centre for Inflammation Research, The University of Edinburgh, Edinburgh, United Kingdom., Gardiner HJ; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom., Rostron AJ; Sunderland Royal Hospital, South Tyneside and Sunderland National Health Service Foundation Trust, Sunderland, United Kingdom.; Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Bannard-Smith J; Department of Critical Care, Manchester Royal Infirmary, Manchester, United Kingdom., Bentley AM; Acute Intensive Care Unit, Wythenshawe Hospital, Manchester, United Kingdom., Brealey D; University College Hospital London, London, United Kingdom., Campbell C; Northern Ireland Clinical Trials Unit, Belfast, United Kingdom., Curley G; Royal College of Surgeons in Ireland, Dublin, Ireland., Clarke M; Northern Ireland Clinical Trials Unit, Belfast, United Kingdom., Dushianthan A; University Hospital Southampton, Southampton, United Kingdom.; National Institute for Health and Care Research Southampton Biomedical Research Centre, University of Southampton, Southampton, United Kingdom., Hopkins P; King's Trauma Centre, King's College Hospital, London, United Kingdom., Jackson C; Northern Ireland Clinical Trials Unit, Belfast, United Kingdom., Kefela K; Department of Critical Care, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom., Krasnodembskaya A; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom., Laffey JG; Regenerative Medicine Institute at CÚRAM Centre for Research in Medical Devices, University of Galway, Galway, Ireland., McDowell C; Northern Ireland Clinical Trials Unit, Belfast, United Kingdom., McFarland M; Department of Critical Care, Belfast Health and Social Care Trust, Belfast, United Kingdom., McFerran J; Northern Ireland Clinical Trials Unit, Belfast, United Kingdom., McGuigan P; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom.; Department of Critical Care, Belfast Health and Social Care Trust, Belfast, United Kingdom., Perkins GD; Critical Care Unit, University Hospitals Birmingham, Birmingham, United Kingdom.; Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, United Kingdom., Silversides J; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom.; Department of Critical Care, Belfast Health and Social Care Trust, Belfast, United Kingdom., Smythe J; National Health Service Blood and Transplant, Oxford, United Kingdom., Thompson J; National Health Service Blood and Transplant, Birmingham, United Kingdom., Tunnicliffe WS; Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom., Welters IDM; Intensive Care Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom.; Institute of Life Course Medical Sciences, University of Liverpool, Liverpool Centre for Cardiovascular Science, Liverpool, United Kingdom., Amado-Rodríguez L; Centro de Investigación Biomédica en Red-Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain.; Unidad de Cuidados Intensivos Cardiológicos, Hospital Universitario Central de Asturias, Oviedo, Spain., Albaiceta G; Centro de Investigación Biomédica en Red-Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain.; Unidad de Cuidados Intensivos Cardiológicos, Hospital Universitario Central de Asturias, Oviedo, Spain.; Departamento de Biología Funcional, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain; and., Williams B; Independent Patient and Public Representative, Sherborne, United Kingdom., Shankar-Hari M; Centre for Inflammation Research, The University of Edinburgh, Edinburgh, United Kingdom., McAuley DF; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom.; Department of Critical Care, Belfast Health and Social Care Trust, Belfast, United Kingdom., O'Kane CM; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom.
Jazyk:	angličtina
Zdroj:	American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2023 Aug 01; Vol. 208 (3), pp. 256-269.
DOI:	10.1164/rccm.202302-0297OC
Abstrakt:	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 (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 O 2 :Fi O 2 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 H 2 O/kPa; placebo, 96.6 [67.3] cm H 2 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. 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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu