Official Title
Mesenchymal Stromal Cells for the Treatment of Moderate to Severe COVID-19 Acute Respiratory Distress Syndrome
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.

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


- 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)


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.

Active, not recruiting
Mesenchymal Stromal Cells
Acute Respiratory Distress Syndrome

Biological: Remestemcel-L
administered twice during the first week, with the second infusion at 4 days following the first injection (± 1 day)
Remestemcel-L Plus Standard of Care

Drug: Placebo
administered twice during the first week, with second infusion at 4 days following the first injection (± 1 day)
Placebo Plus Standard of Care

Eligibility Criteria

Inclusion Criteria - 18 years or older - Patient has SARS-CoV-2 (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 computerized 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) or CRP serum level >4.0 mg/dL - Acute Physiologic and Chronic Health Evaluation (APACHE IV) score >5 - Creatinine clearance of ≥ 30 mL/minute OR a creatinine clearance of 20-29 mL/minute with urine output of ≥0.3 mLs/kg/hour over the last 8 hours or ≥500 mLs over the last 24 hours - 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 BMI >55 - Patients with untreated HIV infection - Patients with malignancy who are within 12 months of active treatment with any chemotherapy, radiation or immunotherapy. - Patients who have been intubated for more than 72 hours in total at the time of randomization - Creatinine clearance less than 20 mL/minute or receiving renal replacement therapy - LFTs (isolated ALT or AST) > 8x upper limit of normal or > 5x upper limit of normal in the setting of other liver function abnormalities (i.e., total bilirubin ≥ 2x upper limit of 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

Eligibility Gender
Eligibility Age
Minimum: 18 Years
United States

Dignity Health
Gilbert, Arizona, 85297

University of Southern California
Los Angeles, California, 90033

Stanford University
Stanford, California, 94305

Emory University
Atlanta, Georgia, 30308

Lutheran Hospital
Fort Wayne, Indiana, 46825

Ochsner Clinic
New Orleans, Louisiana, 70121

Maine Medical Center
Portland, Maine, 04102

University of Maryland
Baltimore, Maryland, 21201

Brigham and Women's Hospital
Boston, Massachusetts, 02115

University of Michigan
Ann Arbor, Michigan, 48109

Lebanon, New Hampshire, 03766

New York University Langone Health
New York, New York, 10016

Mount Sinai Health
New York, New York, 10029

Northwell Health
New York, New York, 10075

Duke University Medical Center
Durham, North Carolina, 27710

Raleigh, North Carolina, 27610

Cleveland Clinic Foundation
Cleveland, Ohio, 44195

University of Pennsylvania Health System
Philadelphia, Pennsylvania, 19104

Houston Methodist Hospital
Houston, Texas, 77030

Baylor, Smith & White
Plano, Texas, 75093

University of Virginia
Charlottesville, Virginia, 22908

Annetine C Gelijns, PhD
Principal Investigator
Icahn School of Medicine at Mount Sinai


Michael Mack, MD
Study Director
Baylor Research Institute


Peter Smith, MD
Study Director
Duke University

Icahn School of Medicine at Mount Sinai
Mesoblast, Inc.
National Heart, Lung, and Blood Institute (NHLBI)
NCT Number
mesenchymal stem cells
Cytokine storm
MeSH Terms
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury