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Trial record 1 of 1 for:    Remestemcel | Covid-19 | Cleveland, Ohio, U.S.
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MSCs in COVID-19 ARDS

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ClinicalTrials.gov Identifier: NCT04371393
Recruitment Status : Recruiting
First Posted : May 1, 2020
Last Update Posted : May 21, 2020
Sponsor:
Collaborator:
Mesoblast, Inc.
Information provided by (Responsible Party):
Annetine Gelijns, Icahn School of Medicine at Mount Sinai

Brief Summary:

The mortality rate in SARS-CoV-2-related severe ARDS is high despite treatment with antivirals, glucocorticoids, immunoglobulins, and ventilation. Preclinical and clinical evidence indicate that MSCs migrate to the lung and respond to the pro-inflammatory lung environment by releasing anti-inflammatory factors reducing the proliferation of pro-inflammatory cytokines while modulating regulatory T cells and macrophages to promote resolution of inflammation. Therefore, MSCs may have the potential to increase survival in management of COVID-19 induced ARDS.

The primary objective of this phase 3 trial is to evaluate the efficacy and safety of the addition of the mesenchymal stromal cell (MSC) remestemcel-L plus standard of care compared to placebo plus standard of care in patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2. The secondary objective is to assess the impact of MSCs on inflammatory biomarkers.


Condition or disease Intervention/treatment Phase
Mesenchymal Stromal Cells Remestemcel-L Biological: Remestemcel-L Drug: Placebo Phase 3

Detailed Description:

This will be a randomized (1:1 ratio), double blind, parallel design, placebo controlled trial. Randomization will be stratified by clinical center and by moderate versus severe ARDS. The study is designed to have three interim analyses for stopping accrual early for efficacy and futility when 30%, 45% and 60% of the 300 patients have reached the primary endpoint using Bayesian predictive probabilities.

Patients will be randomized in a 1:1 allocation to intravenous infusion of MSCs (remestemcel-L) plus standard of care versus placebo plus standard of care for the treatment of COVID-19 related ARDS:

  • Group 1: 2x10^6 MSC/kg of body weight plus standard of care, administered twice during the first week, with the second infusion at 4 days following the first infusion (± 1 day)
  • Group 2: Placebo (Plasma-Lyte) plus standard of care, administered twice during the first week, with the second infusion at 4 days following the first infusion (± 1 day) (control)

MSCs and placebo will initially be administered intravenously in the dose defined above at randomization. The rate of infusion may be tailored to the patient's respiratory status and fluid status, but the duration of infusion should not exceed 60 minutes.

Patients will be followed for 90 days post randomization, with assessment of pulmonary symptoms at 6 and 12 months.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This will be a randomized (1:1 ratio), double blind, parallel design, placebo controlled trial.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: This is a randomized clinical trial, in which the patients and investigators are masked to treatment assignment.
Primary Purpose: Treatment
Official Title: Mesenchymal Stem Cells for the Treatment of Moderate to Severe COVID-19 Acute Respiratory Distress Syndrome
Actual Study Start Date : April 30, 2020
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2022


Arm Intervention/treatment
Experimental: Remestemcel-L Plus Standard of Care
Intravenous infusion of remestemcel-L 2x10^6 MSC/kg of body weight plus standard of care
Biological: Remestemcel-L
administered twice during the first week, with the second infusion at 4 days following the first injection (± 1 day)

Placebo Comparator: Placebo Plus Standard of Care
Placebo (Plasma-Lyte) plus standard of care
Drug: Placebo
administered twice during the first week, with second infusion at 4 days following the first injection (± 1 day)




Primary Outcome Measures :
  1. Number of all-cause mortality [ Time Frame: 30 days ]
    Number of all-cause mortality within 30 days of randomization.


Secondary Outcome Measures :
  1. Number of days alive off mechanical ventilatory support [ Time Frame: 60 days ]
    Number of days alive off mechanical ventilatory support calculated as the number of days, within the 60 days window, that patients were alive and free of mechanical ventilatory support.

  2. Number of adverse events [ Time Frame: 30 days ]
    Safety analyses will be assessed by adverse event rates calculated as the ratio of the total number of events over 30 days divided by total patient-time at risk for the specific event from randomization.

  3. Number of participants alive at day 7 [ Time Frame: 7 days ]
  4. Number of participants alive at day 14 [ Time Frame: 14 days ]
  5. Number of participants alive at day 60 [ Time Frame: 60 days ]
  6. Number of participants alive at day 90 [ Time Frame: 90 days ]
  7. Number of participants with resolution and/or improvement of ARDS [ Time Frame: 7 days ]
    The number and percent of patients with resolution and/or improvement of ARDS at day 7

  8. Number of participants with resolution and/or improvement of ARDS [ Time Frame: 14 days ]
    The number and percent of patients with resolution and/or improvement of ARDS at day 14

  9. Number of participants with resolution and/or improvement of ARDS [ Time Frame: 21 days ]
    The number and percent of patients with resolution and/or improvement of ARDS at day 21

  10. Number of participants with resolution and/or improvement of ARDS [ Time Frame: 30 days ]
    The number and percent of patients with resolution and/or improvement of ARDS at day 30

  11. Change from baseline of the severity of ARDS [ Time Frame: baseline and 7 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 7 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

  12. Change from baseline of the severity of ARDS [ Time Frame: baseline and 14 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 14 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

  13. Change from baseline of the severity of ARDS [ Time Frame: baseline and 21 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 21 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

  14. Change from baseline of the severity of ARDS [ Time Frame: baseline and 30 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 30 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

  15. Length of stay [ Time Frame: 12 months ]
    Hospital length of stay

  16. Clinical Improvement Scale [ Time Frame: 7 days ]
    Change from baseline in Clinical Improvement Scale at day 7. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

  17. Clinical Improvement Scale [ Time Frame: 14 days ]
    Change from baseline in Clinical Improvement Scale at day 14. Full scale from 1 to 7, with higher score indicating more clinical improvement.

  18. Clinical Improvement Scale [ Time Frame: 21 days ]
    Change from baseline in Clinical Improvement Scale at day 21. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

  19. Clinical Improvement Scale [ Time Frame: 30 days ]
    Change from baseline in Clinical Improvement Scale at day 30. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

  20. Change in serum hs-CRP concentration [ Time Frame: baseline and 7 days ]
    Changes from baseline in serum hs-CRP concentration at days 7

  21. Change in serum hs-CRP concentration [ Time Frame: baseline and 14 days ]
    Changes from baseline in serum hs-CRP concentration at days 14

  22. Change in serum hs-CRP concentration [ Time Frame: baseline and 21 days ]
    Changes from baseline in serum hs-CRP concentration at days 21

  23. Change in serum hs-CRP concentration [ Time Frame: baseline and 30 days ]
    Changes from baseline in serum hs-CRP concentration at days 30

  24. Change in IL-6 inflammatory marker level [ Time Frame: baseline and 7 days ]
    Changes from baseline in IL-6 inflammatory marker level at 7 days

  25. Change in IL-6 inflammatory marker level [ Time Frame: baseline and 14 days ]
    Changes from baseline in IL-6 inflammatory marker level at 14 days

  26. Change in IL-6 inflammatory marker level [ Time Frame: baseline and 21 days ]
    Changes from baseline in IL-6 inflammatory marker level at 21 days

  27. Change in IL-6 inflammatory marker level [ Time Frame: baseline and 30 days ]
    Changes from baseline in IL-6 inflammatory marker level at 30 days

  28. Change in IL-8 inflammatory marker level [ Time Frame: baseline and 7 days ]
    Changes from baseline in IL-6 inflammatory marker level at 7 days

  29. Change in IL-8 inflammatory marker level [ Time Frame: baseline and 14 days ]
    Changes from baseline in IL-6 inflammatory marker level at 14 days

  30. Change in IL-8 inflammatory marker level [ Time Frame: baseline and 21 days ]
    Changes from baseline in IL-6 inflammatory marker level at 21 days

  31. Change in IL-8 inflammatory marker level [ Time Frame: baseline and 30 days ]
    Changes from baseline in IL-6 inflammatory marker level at 30 days

  32. Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 7 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 7 days

  33. Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 14 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 14 days

  34. Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 21 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 21 days

  35. Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 30 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 30 days



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • 18 years or older
  • Patient has coronavirus disease COVID-19 confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR) assay or other diagnostic test
  • Patient requiring mechanical ventilatory support with moderate to severe ARDS as determined by the following criteria (adapted from the Berlin criteria)

    • Bilateral opacities must be present on a chest radiograph or computed tomographic (CT) scan. These opacities are not fully explained by pleural effusions, lobar collapse, lung collapse, or pulmonary nodules.
    • Respiratory failure not fully explained by cardiac failure or fluid overload.
    • Moderate to severe impairment of oxygenation must be present, as defined by the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2). The severity of the hypoxemia defines the severity of the ARDS:
  • Moderate ARDS: PaO2/FiO2 >100 mmHg and ≤200 mmHg, on ventilator settings that include PEEP ≥5 cm H2O OR
  • Severe ARDS: PaO2/FiO2 ≤100 mmHg on ventilator settings that include PEEP ≥5 cm H2O
  • High sensitivity C-Reactive Protein (hs-CRP) serum level >4.0 mg/dL
  • Acute Physiologic and Chronic Health Evaluation (APACHE IV) score >5
  • The patient or his/her legally authorized representative (LAR) is able to provide informed consent

Exclusion Criteria

  • Currently receiving extracorporeal membrane oxygenation (ECMO) or high frequency oscillatory ventilation (HFOV)
  • Females who are pregnant or lactating
  • Patients with established positive bacterial blood cultures prior to enrollment or suspicion of superimposed bacterial pneumonia
  • Patients with untreated HIV infection
  • Patients who have been intubated for more than 72 hours
  • Creatinine clearance less than 30 mL/minute
  • LFTs (ALT or AST) > 5x normal
  • Known hypersensitivity to DMSO or to porcine or bovine proteins
  • History of prior respiratory disease with requirement for supplemental oxygen
  • Any end-stage organ disease which in the opinion of the investigator may possibly affect the safety of remestemcel-L treatment
  • Receiving an investigational cellular therapy agent

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): NCT04371393


Contacts
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Contact: Mary Beth Marks (212) 659-9699 mary.marks@mountsinai.org

Locations
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United States, California
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Contact: Edward Lozano       edwardlo@med.usc.edu   
Principal Investigator: Michael Bowdish, MD         
United States, Georgia
Emory University Not yet recruiting
Atlanta, Georgia, United States, 30308
Contact: Chari Ponder       chari.ponder@emory.edu   
Principal Investigator: Bradley Leshnower, MD         
United States, Indiana
Lutheran Hospital Recruiting
Fort Wayne, Indiana, United States, 46825
Contact: Sharon Eichman       SEichman@Lutheran-Hosp.com   
Principal Investigator: Eustace Fernandes, MD         
United States, Louisiana
Ochsner Clinic Recruiting
New Orleans, Louisiana, United States, 70121
Contact: Sylvia Laudun       slaudun@ochsner.org   
Principal Investigator: P. Eugene Parrino, MD         
United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Contact: Manal Al-Suqi       MaAl-Suqi@som.umaryland.edu   
Principal Investigator: Sunjay Kaushal, MD         
United States, Massachusetts
Brigham and Women's Hospital Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Guruprasad Jambaulikar       GJAMBAULIKAR@BWH.HARVARD.EDU   
Principal Investigator: Peter Hou, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Lydia McGowan       lydiamcg@umich.edu   
Principal Investigator: Jonathan Golob, MD         
United States, New Hampshire
Dartmouth-Hitchcock Recruiting
Lebanon, New Hampshire, United States, 03766
Contact: Hank Stokes       henry.c.stokes@hitchcock.org   
Principal Investigator: Alex Iribarne, MD         
United States, New York
Mount Sinai Health Recruiting
New York, New York, United States, 10029
Contact: Alexis Mark       alexis.mark@mssm.edu   
Principal Investigator: Keren Osman, MD         
Northwell Health Recruiting
New York, New York, United States, 10075
Contact: Effe Mihelis       EMihelis@northwell.edu   
Principal Investigator: Nirav Patel         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Kathleen Lane       kathleen.rohrback@duke.edu   
Principal Investigator: Peter Smith, MD         
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Denise Kosty-Sweeney       sweened2@ccf.org   
Principal Investigator: Abhijit Duggal         
United States, Pennsylvania
University of Pennsylvania Health System Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Mary Lou Mayer       MaryLou.Mayer@uphs.upenn.edu   
Principal Investigator: Nimesh Desai, MD         
United States, Texas
Baylor, Smith & White Recruiting
Plano, Texas, United States, 75093
Contact: Rehma Shabbir         
Principal Investigator: Robert Gottliebb, MD         
United States, Virginia
University of Virginia Not yet recruiting
Charlottesville, Virginia, United States, 22908
Contact: China Green       cgreen@virginia.edu   
Principal Investigator: Jeffrey Sturek, MD         
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
Mesoblast, Inc.
Investigators
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Principal Investigator: Annetine C Gelijns, PhD Icahn School of Medicine at Mount Sinai
Study Director: Michael Mack, MD Baylor Research Institute
Study Director: Peter Smith, MD Duke University
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Responsible Party: Annetine Gelijns, Chair, Department of Population Health Science & Policy, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT04371393    
Other Study ID Numbers: GCO 08-1078-0014
First Posted: May 1, 2020    Key Record Dates
Last Update Posted: May 21, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All of the individual participant data collected during the trial, after deidentification.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: De-identified study data sets must be submitted to the designated NHLBI Program Official no later than 3 years after the end of the clinical activity (final patient follow-up, etc.) or 2 years after the main paper of the trial has been published, whichever comes first. Data are prepared by the study coordinating center and sent to the designated PO for review prior to release.
Access Criteria: Anyone who wishes to access the data.

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