Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial)

被引：16

作者：

Gorman, Ellen A. ^{[1
]}

Rynne, Jennifer ^{[2
]}

Gardiner, Hannah J. ^{[1
]}

Rostron, Anthony J. ^{[3
,4
]}

Bannard-Smith, Jonathan ^{[5
]}

Bentley, Andrew M. ^{[6
]}

Brealey, David ^{[7
]}

Campbell, Christina ^{[8
]}

Curley, Gerard ^{[9
]}

Clarke, Mike ^{[8
]}

Dushianthan, Ahilanadan ^{[10
,11
]}

Hopkins, Phillip ^{[12
]}

Jackson, Colette ^{[8
]}

Kefela, Kallirroi ^{[13
]}

Krasnodembskaya, Anna ^{[1
]}

Laffey, John G. ^{[14
]}

McDowell, Cliona ^{[8
]}

McFarland, Margaret ^{[15
]}

McFerran, Jamie ^{[8
]}

McGuigan, Peter ^{[1
,15
]}

Perkins, Gavin D. ^{[16
,17
]}

Silversides, Jonathan ^{[1
]}

Smythe, Jon ^{[18
]}

Thompson, Jacqui ^{[19
]}

Tunnicliffe, William S. ^{[20
]}

Welters, Ingeborg D. M. ^{[21
,22
]}

Amado-Rodriguez, Laura ^{[23
,24
,25
]}

Albaiceta, Guillermo ^{[23
,24
,25
,26
]}

Williams, Barry ^{[27
]}

Shankar-Hari, Manu ^{[2
]}

McAuley, Daniel F. ^{[1
]}

O'Kane, Cecilia M. ^{[1
]}

机构：

[1] Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, Belfast, Antrim, North Ireland

[2] Univ Edinburgh, Ctr Inflammat Res, Edinburgh, Midlothian, Scotland

[3] Sunderland Royal Hosp, South Tyneside & Sunderland Natl Hlth Serv Fdn Tr, Sunderland, England

[4] Newcastle Univ, Clin Res Inst, Newcastle Upon Tyne, Tyne & Wear, England

[5] Manchester Royal Infirm, Dept Crit Care, Manchester, Lancs, England

[6] Wythenshawe Hosp, Acute Intens Care Unit, Manchester, Lancs, England

[7] Univ Coll London Hosp, London, ON, Canada

[8] Northern Ireland Clin Trials Unit, Belfast, Antrim, North Ireland

[9] Royal Coll Surgeons Ireland, Dublin, Ireland

[10] Southampton Univ Hosp, Southampton, Hants, England

[11] Univ Southampton, Natl Inst Hlth & Care Res Southampton Biomed Res, Southampton, Hants, England

[12] Kings Coll Hosp London, Kings Trauma Ctr, London, England

[13] Royal Infirm Edinburgh NHS Trust, Dept Crit Care, Edinburgh, Midlothian, Scotland

[14] Univ Galway, Regenerat Med Inst, C RAM Ctr Res Med Devices, Galway, Ireland

[15] Belfast Hlth & Social Care Trust, Dept Crit Care, Belfast, Antrim, North Ireland

[16] Univ Hosp Birmingham, Crit Care Unit, Birmingham, W Midlands, England

[17] Univ Warwick, Warwick Med Sch, Warwick Clin Trials Unit, Coventry, W Midlands, England

[18] Natl Hlth Serv Blood & Transplant, Birmingham, W Midlands, England

[19] Natl Hlth Serv Blood & Transplant, Birmingham, W Midlands, England

[20] Queen Elizabeth Hosp Birmingham, Birmingham, W Midlands, England

[21] Royal Liverpool Univ Hosp, Intens Care Unit, Liverpool, Merseyside, England

[22] Univ Liverpool, Inst Life Course Med Sci, Liverpool Ctr Cardiovasc Sci, Liverpool, Merseyside, England

[23] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Resp, Madrid, Spain

[24] Inst Invest Sanitaria Principado Asturias, Oviedo, Spain

[25] Hosp Univ Cent Asturias, Unidad Cuidados Intens Cardiol, Oviedo, Spain

[26] Univ Oviedo, Inst Univ Oncol Principado Asturias, Dept Biol Func, Oviedo, Spain

[27] Independent Patient & Publ Representat, Sherborne, England

来源：

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE | 2023年 / 208卷 / 03期

基金：

英国惠康基金;

关键词：

acute respiratory distress syndrome; coronavirus disease; mesenchymal stromal cells; clinical trial; MESENCHYMAL STEM-CELLS; ACUTE LUNG INJURY; BONE-MARROW; ADMINISTRATION REALIST; MITOCHONDRIAL TRANSFER; MACROPHAGES; MANAGEMENT; MODELS; BLIND; ARDS;

D O I：

10.1164/rccm.202302-0297OC

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

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.

引用

页码：256 / 269

页数：14

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