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

Accepted/In Press date: 5 May 2023

Published date: 8 May 2023

Additional Information: Funding Information: Supported by the Wellcome Trust Health Innovation Challenge Fund (reference 106939/Z/15/Z) and the Northern Ireland Health and Social Care Research and Development Fund for needs-led research. The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. Orbsen Therapeutics Ltd. has granted a nonexclusive, trial-specific license to the Cellular and Molecular Therapies Division of the National Health Service Blood and Transplant Service to manufacture ORBCEL-C to Good Manufacturing Practice standards for the REALIST trial. Orbsen Therapeutics Ltd. had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. The authors acknowledge all patients who participated in the REALIST trial and their legal representatives; clinical research teams at each clinical site who participated in patient recruitment, data collection, and patient follow-up; clinical teams at each site who provided clinical care to patients involved in the study; pharmacy and cell therapy facility staff members at each clinical site for oversight and management of the study drugs; staff members at National Health Service Blood and Transplant involved in the manufacture and distribution of ORBCEL-C; staff members at Victoria Pharmaceuticals involved in the manufacture and distribution of placebo; staff members at the Northern Ireland Clinical Trials Unit for support in the conduct of the trial; staff members at Queen’s University Belfast who supported laboratory analysis; members of the data monitoring and ethics committee (Professor John Norrie, Professor Mervyn Singer, and Professor Sam Janes); and members of the trial steering committee (Professor Charles Hinds, Professor John Simpson, Professor Mike Grocott, Mr. Barry Williams, and Professor John Laffey). The authors acknowledge Dr. David Oliver Hamilton for his effort in recruiting patients at Liverpool Royal Infirmary. Funding Information: Supported by the Wellcome Trust Health Innovation Challenge Fund (reference 106939/Z/15/Z) and the Northern Ireland Health and Social Care Research and Development Fund for needs-led research. The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. Orbsen Therapeutics Ltd. has granted a nonexclusive, trial-specific license to the Cellular and Molecular Therapies Division of the National Health Service Blood and Transplant Service to manufacture ORBCEL-C to Good Manufacturing Practice standards for the REALIST trial. Orbsen Therapeutics Ltd. had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. Funding Information: REALIST-COVID (NCT 03042143) was a multicenter randomized, double-blind, allocation-concealed, placebo-controlled trial of ORBCEL-C MSCs in patients with ARDS due to COVID-19 in 12 ICUs across the United Kingdom. Full details of the study design have been published (37) and are available in the online supplement. The trial was sponsored by Belfast Health and Social Care Trust and approved by the North-East York research ethics committee (18/NE/ 0006) and the Medicines and Healthcare Products Regulatory Agency (European Union Drug Regulating Authorities Clinical Trials Database number 2017-000584-33). In brief, after informed consent was obtained, eligible patients who were mechanically ventilated within 72 hours of the onset of moderate to severe ARDS due to COVID-19 were randomized (1:1) to receive a single intravenous infusion of either ORBCEL-C (400 3 106 CD362-enriched umbilical cord–derived MSCs in 200 ml Plasma-Lyte 148; see theonlinesupplement for manufacturing details, including cell viability assessment) or placebo (Baxter Healthcare Ltd.) (200 ml Plasma-Lyte 148). All other aspects of carewereaccording to standard critical care guidelines (4). Publisher Copyright: Copyright © 2023 by the American Thoracic Society.

Keywords: acute respiratory distress syndrome, clinical trial, coronavirus disease, mesenchymal stromal cells

Local EPrints ID: 480363

URI: http://eprints.soton.ac.uk/id/eprint/480363

DOI: doi:10.1164/rccm.202302-0297OC

ISSN: 1073-449X

PURE UUID: 50114102-e281-497f-8dcf-5e10c84d11ac

ORCID for Ahilanadan Dushianthan: orcid.org/0000-0002-0165-3359

Date deposited: 01 Aug 2023 17:52

Last modified: 17 Mar 2024 03:51