Repair of acute respiratory distress syndrome by stromal cell administration (REALIST) trial: A phase 1 trial

被引:23
|
作者
Gorman, Ellen [1 ]
Shankar-Hari, Manu [2 ,3 ]
Hopkins, Phil [4 ]
Tunnicliffe, William S. [5 ]
Perkins, Gavin D. [6 ,7 ]
Silversides, Jonathan [1 ,8 ]
McGuigan, Peter [8 ]
Krasnodembskaya, Anna [1 ]
Jackson, Colette [9 ]
Boyle, Roisin [9 ]
McFerran, Jamie [9 ]
McDowell, Cliona [9 ]
Campbell, Christina [9 ]
McFarland, Margaret [8 ]
Smythe, Jon [10 ]
Thompson, Jacqui [11 ]
Williams, Barry
Curley, Gerard [12 ]
Laffey, John G. [13 ]
Clarke, Mike [9 ,14 ]
McAuley, Daniel F. [1 ]
O'Kane, Cecilia M. [1 ]
机构
[1] Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland
[2] Guys & St Thomas NHS Fdn Trust, Westminister Bridge Rd, London SE1 7EH, England
[3] Kings Coll London, Sch Immunol & Microbial Sci, London WC2R 2IS, England
[4] Kings Coll London, Kings Trauma Ctr, London WC2R 2LS, England
[5] Queen Elizabeth Hosp Birmingham, Mindelsohn Way, Birmingham B15 2GW, W Midlands, England
[6] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England
[7] Univ Hosp Birmingham, Mindelsohn Way, Birmingham B15 2GW, W Midlands, England
[8] Belfast Hlth & Social Care Trust, Royal Victoria Hosp, 274 Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland
[9] Northern Ireland Clin Trials Unit, 7 Lennoxvale, Belfast BT9 5BY, Antrim, North Ireland
[10] NHS Blood & Transplant, Headley Way, Oxford 0X3 9BU, England
[11] NHS Blood & Transplant Serv, Vincent Dr, Birmingham B15 2SG, W Midlands, England
[12] Royal Coll Surgeons Ireland, Dublin 9, Ireland
[13] Natl Univ Ireland Galway, Regenerat Med Inst REMEDI, CURAM Ctr Res Med Devices, Univ Rd, Galway H91 TK33, Ireland
[14] Queens Univ Belfast, Northern Ireland Methodol Hub, Sch Med Dent & Biomed Sci, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland
基金
英国惠康基金;
关键词
MESENCHYMAL STEM-CELLS; ACUTE LUNG INJURY; INTENSIVE-CARE UNITS; ESCHERICHIA-COLI; MITOCHONDRIAL TRANSFER; CLINICAL-OUTCOMES; PRECURSOR CELLS; E; COLI; SECRETION; SEVERITY;
D O I
10.1016/j.eclinm.2021.101167
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Mesenchymal stromal cells (MSCs) may be of benefit in acute respiratory distress syndrome (ARDS) due to immunomodulatory, reparative, and antimicrobial actions. ORBCEL-C isa population of CD362 enriched umbilical cord-derived MSCs. The REALIST phase 1 trial investigated the safety and feasibility of ORBCEL-C in patients with moderate to severe ARDS. Methods: REALIST phase 1 was an open label, dose escalation trial in which cohorts of mechanically venti-lated patients with moderate to severe ARDS received increasing doses (100, 200 or 400 x 10(6) cells) of a sin-gle intravenous infusion of ORBCEL-C in a 3 + 3 design. The primary safety outcome was the incidence of serious adverse events. Dose limiting toxicity was defined as a serious adverse reaction within seven days. Trial registration clinicaltrials.gov NCT03042143. Findings: Nine patients were recruited between the 7th January 2019 and 14th January 2020. Study drug admin-istration was well tolerated and no dose limiting toxicity was reported in any of the three cohorts. Eight adverse events were reported for four patients. Pyrexia within 24 h of study drug administration was reported in two patients as pre-specified adverse events. A further two adverse events (non-sustained ventricular tachycardia and deranged liver enzymes), were reported as adverse reactions. Four serious adverse events were reported (colonic perforation, gastric perforation, bradycardia and myocarditis) but none were deemed related to adminis-tration of ORBCEL-C. At day 28 no patients had died in cohort one (100 x 10(6)), three patients had died in cohort two (200 x 10(6)) and one patient had died in cohort three (400 x 10(6)). Overall day 28 mortality was 44% (n = 4/9). Interpretation: A single intravenous infusion of ORBCEL-C was well tolerated in patients with moderate to severe ARDS. No dose limiting toxicity was reported up to 400 x 10(6) cells. (C) 2021 The Author(s). Published by Elsevier Ltd.
引用
收藏
页数:12
相关论文
共 50 条
  • [1] Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cell Administration (REALIST-COVID) Phase 2 Randomised Controlled Trial
    Gorman, E.
    McAuley, D. F.
    Rostron, A. J.
    Shankar-Hari, M.
    Bannard-Smith, J.
    Bentley, A. M.
    Brealey, D.
    Campbell, C.
    Curley, G.
    Clarke, M.
    Dushianthan, A.
    Hopkins, P.
    Jackson, C.
    Kefala, K.
    Krasnodembskaya, A.
    Laffey, J. G.
    McDowell, C.
    McFarland, M.
    McFerran, J.
    McGuigan, P.
    Perkins, G. D.
    Silversides, J.
    Smythe, J.
    Thompson, J.
    Tunnicliffe, W. S.
    Welters, I. D. M.
    Williams, B.
    O'Kane, C. M.
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2022, 205
  • [2] Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial)
    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-Rodriguez, Laura
    Albaiceta, Guillermo
    Williams, Barry
    Shankar-Hari, Manu
    McAuley, Daniel F.
    O'Kane, Cecilia M.
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2023, 208 (03) : 256 - 269
  • [3] Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration in COVID-19 (REALIST-COVID-19): A structured summary of a study protocol for a randomised, controlled trial
    Gorman, Ellen
    Shankar-Hari, Manu
    Hopkins, Phil
    Tunnicliffe, William S.
    Perkins, Gavin D.
    Silversides, Jonathan
    McGuigan, Peter
    Jackson, Colette
    Boyle, Roisin
    McFerran, Jamie
    McDowell, Cliona
    Campbell, Christina
    McFarland, Margaret
    Smythe, Jon
    Thompson, Jacqui
    Williams, Barry
    Curley, Gerard
    Laffey, John G.
    Clarke, Mike
    O'Kane, Cecilia
    McAuley, Daniel F.
    [J]. TRIALS, 2020, 21 (01)
  • [4] Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration in COVID-19 (REALIST-COVID-19): A structured summary of a study protocol for a randomised, controlled trial
    Ellen Gorman
    Manu Shankar-Hari
    Phil Hopkins
    William S. Tunnicliffe
    Gavin D. Perkins
    Jonathan Silversides
    Peter McGuigan
    Colette Jackson
    Roisin Boyle
    Jamie McFerran
    Cliona McDowell
    Christina Campbell
    Margaret McFarland
    Jon Smythe
    Jacqui Thompson
    Barry Williams
    Gerard Curley
    John G. Laffey
    Mike Clarke
    Cecilia O’Kane
    Daniel F. McAuley
    [J]. Trials, 21
  • [5] Repair of acute respiratory distress syndrome by stromal cell administration (REALIST): a structured study protocol for an open-label dose-escalation phase 1 trial followed by a randomised, triple-blind, allocation concealed, placebo- controlled phase 2 trial
    Gorman, Ellen
    Shankar-Hari, Manu
    Hopkins, Phil
    Tunnicliffe, William S.
    Perkins, Gavin D.
    Silversides, Jonathan
    McGuigan, Peter
    Jackson, Colette
    Boyle, Roisin
    McFerran, Jamie
    McDowell, Cliona
    Campbell, Christina
    McFarland, Margaret
    Smythe, Jon
    Thompson, Jacqui
    Williams, Barry
    Curley, Gerard
    Laffey, John G.
    Clarke, Mike
    McAuley, Daniel F.
    O'Kane, Cecilia
    [J]. TRIALS, 2022, 23 (01)
  • [6] Repair of acute respiratory distress syndrome by stromal cell administration (REALIST): a structured study protocol for an open-label dose-escalation phase 1 trial followed by a randomised, triple-blind, allocation concealed, placebo-controlled phase 2 trial
    Ellen Gorman
    Manu Shankar-Hari
    Phil Hopkins
    William S. Tunnicliffe
    Gavin D. Perkins
    Jonathan Silversides
    Peter McGuigan
    Colette Jackson
    Roisin Boyle
    Jamie McFerran
    Cliona McDowell
    Christina Campbell
    Margaret McFarland
    Jon Smythe
    Jacqui Thompson
    Barry Williams
    Gerard Curley
    John G. Laffey
    Mike Clarke
    Daniel F. McAuley
    Cecilia O’Kane
    [J]. Trials, 23
  • [7] REPAIR OF ACUTE RESPIRATORY DISTRESS SYNDROME IN COVID-19 BY STROMAL CELLS (REALIST-COVID TRIAL): 1 YEAR FOLLOW UP FOR SAFETY AND PULMONARY DYSFUNCTION
    Gardiner, H. J.
    Gorman, E. A.
    Rostron, A. J.
    Shankar-Hari, M.
    Bannard-Smith, J.
    Bentley, A. M.
    Brealey, D.
    Campbell, C.
    Curley, G.
    Clarke, M.
    Dushianthan, A.
    Hopkins, P.
    Jackson, C.
    Kefela, K.
    Laffey, J. G.
    McDowell, C.
    McFarland, M.
    McFerran, J.
    McGuigan, P.
    Perkins, G. D.
    Silversides, J.
    Smythe, J.
    Thompson, J.
    Tunnicliffe, W. S.
    Welters, I. D. M.
    Williams, B.
    McAuley, D. F.
    O'Kane, C. M.
    [J]. THORAX, 2022, 77 : A30 - A30
  • [8] The Relationship of Fluid Administration to Outcome in the Pediatric Calfactant in Acute Respiratory Distress Syndrome Trial
    Willson, Douglas F.
    Thomas, Neal J.
    Tamburro, Robert
    Truemper, Edward
    Truwit, Jonathon
    Conaway, Mark
    Traul, Christine
    Egan, Edmund E.
    [J]. PEDIATRIC CRITICAL CARE MEDICINE, 2013, 14 (07) : 666 - 672
  • [9] The Adult Calfactant in Acute Respiratory Distress Syndrome Trial
    Willson, Douglas F.
    Truwit, Jonathon D.
    Conaway, Mark R.
    Traul, Christine S.
    Egan, Edmund E.
    [J]. CHEST, 2015, 148 (02) : 356 - 364
  • [10] Phase I trial of the recombinant soluble complement receptor 1 in acute lung injury and acute respiratory distress syndrome
    Zimmerman, JL
    Dellinger, RP
    Straube, RC
    Levin, JL
    [J]. CRITICAL CARE MEDICINE, 2000, 28 (09) : 3149 - 3154