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

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ClinicalTrials.gov Identifier: NCT03042143
Recruitment Status : Recruiting
First Posted : February 3, 2017
Last Update Posted : November 27, 2018
Sponsor:
Collaborators:
Queen's University, Belfast
Northern Ireland Clinical Trials Unit
NHS Blood and Transplant
Information provided by (Responsible Party):
Professor Danny McAuley, Belfast Health and Social Care Trust

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. 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. This project will also provide new information about mechanisms in the development of ARDS leading, potentially, to other new treatments

Condition or disease Intervention/treatment Phase
Acute Respiratory Distress Syndrome Biological: Human umbilical cord derived CD362 enriched MSCs Biological: Placebo (Plasma-Lyte 148) Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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.

After 7 days of follow-up for all study subjects in the phase 1 study is available the TMG will review the data and propose a cell dose for the phase 2 trial. This recommendation will be submitted to the DMEC for approval prior to initiating the phase 2 trial.

The phase 2 trial is a randomized, double-blind, allocation concealed placebo-controlled study using the maximal tolerable dose as determined by the DMEC in patients with moderate to severe ARDS.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

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 unauthorized 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.

Primary Purpose: Treatment
Official Title: Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration (REALIST): An Open Label Dose Escalation Phase 1 Trial Followed by a Randomized, Double-blind, Placebo-controlled Phase 2 Trial
Estimated Study Start Date : November 22, 2018
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : October 2022


Arm Intervention/treatment
Experimental: Human umbilical cord derived CD362 enriched MSCs
Maximum tolerated dose from the phase 1 trial will be infused over 30 to 90 mins
Biological: Human umbilical cord derived CD362 enriched MSCs
Infusion of Human umbilical cord derived CD362 enriched MSCs

Placebo Comparator: Placebo (Plasma-Lyte 148) infusion
Plasma-Lyte 148 infused over 30 to 90 mins
Biological: Placebo (Plasma-Lyte 148)
Infusion of placebo




Primary Outcome Measures :
  1. Oxygenation index (OI) [ Time Frame: Day 7 ]
    OI is a physiological index of the severity of ARDS and measures both impaired oxygenation and the amount of mechanical ventilation delivered

  2. Incidence of Serious Adverse Events (SAEs) [ Time Frame: 28 days ]
    Incidence of SAEs


Secondary Outcome Measures :
  1. Oxygenation index [ Time Frame: Days 4 and 14 ]
  2. Sequential Organ Failure Assessment (SOFA) score [ Time Frame: Days 4, 7 and 14 ]
    SOFA score is a measure of organ failure

  3. Respiratory compliance (Crs) [ Time Frame: Days 4, 7 and 14 ]
    Crs is a physiological measure of pulmonary function in ARDS

  4. Partial pressure of arterial oxygen to the fraction of inspired oxygen ratio (P/F ratio) [ Time Frame: Days 4, 7 and 14 ]
    P/F ratio is a physiological measure of pulmonary function in ARDS



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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. ARDS as defined by the Berlin definition.

    1. Onset within 1 week of identified insult.
    2. 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
  2. Patient is receiving invasive mechanical ventilation

Exclusion Criteria:

  1. More than 48 hours from the onset of ARDS.
  2. Age < 16 years.
  3. Patient is known to be pregnant
  4. Participation in a clinical trial of an investigational medicinal product within 30 days.
  5. Major trauma in the prior 5 days.
  6. Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last year.
  7. WHO Class III or IV pulmonary hypertension.
  8. Venous thromboembolism currently receiving anti-coagulation or within the past 3 months
  9. Currently receiving extracorporeal life support (ECLS).
  10. Severe chronic liver disease with Child-Pugh score > 12.
  11. DNAR (Do Not Attempt Resuscitation) order in place.
  12. Treatment withdrawal imminent within 24 hours.
  13. Consent declined.
  14. Prisoners.
  15. Non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available.
  16. Previously enrolled in the REALIST trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03042143


Contacts
Contact: Danny F McAuley, MD 02890976385 d.f.mcauley@qub.ac.uk
Contact: Cecilia O'Kane, Ph.D 02890976385 c.okane@qub.ac.uk

Locations
United Kingdom
Belfast Health and Social Care Trust, Royal Hospitals Recruiting
Belfast, Northern Ireland, United Kingdom, BT12 6BA
Contact: Danny F McAuley, MD       d.f.mcauley@qub.ac.uk   
Contact: Cecilia O'Kane, Ph.D       c.okane@qub.ac.uk   
Sponsors and Collaborators
Belfast Health and Social Care Trust
Queen's University, Belfast
Northern Ireland Clinical Trials Unit
NHS Blood and Transplant
Investigators
Principal Investigator: Danny F McAuley, Professor Belfast Health and Social Care Trust

Responsible Party: Professor Danny McAuley, Professor and Consultant of Intensive Care Medicine, Belfast Health and Social Care Trust
ClinicalTrials.gov Identifier: NCT03042143     History of Changes
Other Study ID Numbers: 16154DMcA-AS
First Posted: February 3, 2017    Key Record Dates
Last Update Posted: November 27, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Professor Danny McAuley, Belfast Health and Social Care Trust:
Acute respiratory distress syndrome
Human umbilical cord-derived mesenchymal stem cells

Additional relevant MeSH terms:
Syndrome
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Disease
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury
Plasma-lyte 148
Ophthalmic Solutions
Pharmaceutical Solutions