Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration (REALIST)
Summary
Acute Respiratory Distress Syndrome (ARDS) causes the lungs to fail due to the collection of fluid in the lungs (pulmonary oedema). ARDS is common in severely ill patients in Intensive Care Units and is associated with a high mortality and a high morbidity in those who survive. ARDS occurs in approximately 20% case of COVID-19 and respiratory failure is the leading cause of mortality. There is a large economic burden with direct healthcare costs, but also indirectly due to the impact on the carer and patient through the patients inability to return to full time employment. There is little evidence for effective drug (pharmacological) treatment for ARDS. There is increasing information that mesenchymal stem cells (MSCs) might be important in treating ARDS. REALIST will investigate if a single infusion of MSCs will help in the treatment of ARDS. The first step will be to first of all determine what dose of MSCs is safe and then divide patients suffering from ARDS into two groups, one of which will get MSCs and the other a harmless dummy (or placebo) infusion, who will then be followed up to determine if lung function improves. If effective this may lead to further research to determine if MSCs are effective in patients with ARDS.
Timeline
- Start
- 2019-01-07
- Primary completion
- 2026-04
- Completion
- 2026-10
Outcome
Missed primary endpoint
paper 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). PMID 37154608 ↗
paper ORBCEL-C MSCs were safe in subjects with moderate to severe COVID-19-related ARDS but did not improve surrogates of pulmonary organ dysfunction. PMID 37154608 ↗
Publications
- Gorman EA, Rynne J, Gardiner HJ, Rostron AJ, Bannard-Smith J, Bentley AM, Brealey D, Campbell C, Curley G, Clarke M, Dushianthan A, Hopkins P, Jackson C, Kefela K, Krasnodembskaya A, Laffey JG, McDowell C, McFarland M, McFerran J, McGuigan P, Perkins GD, Silversides J, Smythe J, Thompson J, Tunnicliffe WS, Welters IDM, Amado-Rodriguez L, Albaiceta G, Williams B, Shankar-Hari M, McAuley DF, O'Kane CM. Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial): A Multicenter, Randomized, Controlled Clinical Trial. Am J Respir Crit Care Med. 2023 Aug 1;208(3):256-269. doi: 10.1164/rccm.202302-0297OC.
- Gorman E, Shankar-Hari M, Hopkins P, Tunnicliffe WS, Perkins GD, Silversides J, McGuigan P, Jackson C, Boyle R, McFerran J, McDowell C, Campbell C, McFarland M, Smythe J, Thompson J, Williams B, Curley G, Laffey JG, Clarke M, McAuley DF, O'Kane C. 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. Trials. 2022 May 13;23(1):401. doi: 10.1186/s13063-022-06220-0.
- Gorman E, Shankar-Hari M, Hopkins P, Tunnicliffe WS, Perkins GD, Silversides J, McGuigan P, Krasnodembskaya A, Jackson C, Boyle R, McFerran J, McDowell C, Campbell C, McFarland M, Smythe J, Thompson J, Williams B, Curley G, Laffey JG, Clarke M, McAuley DF, O'Kane CM. Repair of acute respiratory distress syndrome by stromal cell administration (REALIST) trial: A phase 1 trial. EClinicalMedicine. 2021 Oct 24;41:101167. doi: 10.1016/j.eclinm.2021.101167. eCollection 2021 Nov.
- Gorman E, Shankar-Hari M, Hopkins P, Tunnicliffe WS, Perkins GD, Silversides J, McGuigan P, Jackson C, Boyle R, McFerran J, McDowell C, Campbell C, McFarland M, Smythe J, Thompson J, Williams B, Curley G, Laffey JG, Clarke M, O'Kane C, McAuley DF. 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. Trials. 2020 Jun 3;21(1):462. doi: 10.1186/s13063-020-04416-w.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | ORBCEL-C | Cell therapy | 1e+08 cells | Intravenous |
| Subject | ORBCEL-C | Cell therapy | 2e+08 cells | Intravenous |
| Subject | ORBCEL-C | Cell therapy | 4e+08 cells | Intravenous |