Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration (REALIST)

NCT03042143 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 16154DMcA-AS
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Respiratory Distress Syndrome

Keywords

Acute respiratory distress syndrome; Human umbilical cord-derived mesenchymal stem cells; COVID-19

Outcome Measures

Primary Outcomes (2)

• Oxygenation index (OI)

  OI is a physiological index of the severity of ARDS and measures both impaired oxygenation and the amount of mechanical ventilation delivered

  Day 7

• Incidence of Serious Adverse Events (SAEs)

  Incidence of SAEs

  90 days

Secondary Outcomes (9)

• Oxygenation index

  Days 4 and 14

• Sequential Organ Failure Assessment (SOFA) score

  Days 4, 7 and 14

• Respiratory compliance (Crs)

  Days 4, 7 and 14

• Partial pressure of arterial oxygen to the fraction of inspired oxygen ratio (P/F ratio)

  Days 4, 7 and 14

• Driving Pressure

  Days 4, 7 and 14

Study Arms (2)

Human umbilical cord derived CD362 enriched MSCs

EXPERIMENTAL

Maximum tolerated dose from the phase 1 trial will be infused over 30 to 90 mins

Biological: Human umbilical cord derived CD362 enriched MSCs

Placebo (Plasma-Lyte 148) infusion

PLACEBO COMPARATOR

Plasma-Lyte 148 infused over 30 to 90 mins

Biological: Placebo (Plasma-Lyte 148)

Interventions

Human umbilical cord derived CD362 enriched MSCs BIOLOGICAL

Infusion of Human umbilical cord derived CD362 enriched MSCs

Human umbilical cord derived CD362 enriched MSCs

Placebo (Plasma-Lyte 148) BIOLOGICAL

Infusion of placebo

Placebo (Plasma-Lyte 148) infusion

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• ARDS as defined by the Berlin definition.
• Onset within 1 week of identified insult.
• Within the same 24-hour time period i. Hypoxic respiratory failure (PaO2/ FiO2 ratio ≤ 27kPa on PEEP ≥ 5 cmH20) ii. Bilateral infiltrates on chest X-ray consistent with pulmonary oedema not explained by another pulmonary pathology iii. Respiratory failure not fully explained by cardiac failure or fluid overload
• Patient is receiving invasive mechanical ventilation
• COVID-19 based on clinical diagnosis or PCR result or other causes of ARDS.

You may not qualify if:

• More than 72 hours from the onset of ARDS.
• Age \< 16 years.
• Patient is known to be pregnant
• Major trauma in the prior 3 days.
• Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last year.
• WHO Class III or IV pulmonary hypertension.
• Venous thromboembolism currently receiving anti-coagulation or within the past 3 months
• Currently receiving extracorporeal life support (ECLS).
• Severe chronic liver disease with Child-Pugh score \> 12.
• DNAR (Do Not Attempt Resuscitation) order (excluding advance directives) in place.
• Treatment withdrawal imminent within 24 hours.
• Consent declined.
• Prisoners.
• Non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available.
• Previously enrolled in the REALIST trial.

Sponsors & Collaborators

• Belfast Health and Social Care Trust: lead
• Queen's University, Belfast: collaborator
• Northern Ireland Clinical Trials Unit: collaborator
• NHS Blood and Transplant: collaborator

Study Sites (1)

Belfast Health and Social Care Trust, Royal Hospitals

Belfast, Northern Ireland, BT12 6BA, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 37154608 DERIVED

• 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.

  PMID: 35562778 DERIVED

• 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.

  PMID: 34746723 DERIVED

• 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.

  PMID: 32493473 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome; COVID-19

Interventions

Plasma-lyte 148

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Study Officials

• Danny F McAuley, Professor

  Belfast Health and Social Care Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The cell therapy facility and clinical trials pharmacist will be unblinded. The unblinded individuals will keep the treatment information confidential and will not discuss or release information on treatment allocation to the patient, the investigator, or other unauthorised personnel. As in prior studies of MSCs, the infusion bag containing either the cell product or placebo will be masked at the time of preparation in the clinical site's cell therapy facility so that the contents of the infusion bag are not visible to the investigators or to the clinicians who are administering the study drug. The contents of the infusion bag will be administered through a masked infusion set.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Consultant of Intensive Care Medicine

Model Details: The phase 1 trial is an open label dose escalation pilot study in which cohorts of subjects with moderate to severe ARDS will receive increasing doses of a single infusion of Realist Orbcel-C in a 3+3 design. Initially 3 cohorts with 3 subjects/cohort. In the completed Phase 1 REALIST trial, infusion of 400 million cells was achieved without any dose limiting toxicity at day 7 and has been approved by the DMEC as the intervention dose for this study. The phase 2 trial is a randomised, double-blind, allocation concealed placebo-controlled study using the maximal tolerable dose as determined by the DMEC in patients with moderate to severe ARDS due to COVID-19 or other causes of ARDS.

Study Record Dates

• First Submitted: February 1, 2017
• First Posted: February 3, 2017
• Study Start: January 7, 2019
• Primary Completion: April 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: September 8, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)