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CompletedNCT04466098Updated Jan 29, 2025Results posted

Multiple Dosing of Mesenchymal Stromal Cells in Patients With ARDS (COVID-19)

A Phase 2 interventional study of Mesenchymal stromal cells and Placebo in Acute Respiratory Distress Syndrome, ARDS (Moderate or Severe) and COVID-19 Pneumonia, sponsored by Masonic Cancer Center, University of Minnesota. Completed at 2 sites in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2025-01-29.

Sponsored by Masonic Cancer Center, University of Minnesota · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
8
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study summary

This is a multi-center, randomized, placebo controlled, interventional phase 2A trial to evaluate the safety profile and potential efficacy of multi-dosing of mesenchymal stromal cells (MSC) for patients with SARS-CoV-2 associated Acute Respiratory Distress Syndrome (ARDS). After informed consent, treatment assignment will be made by computer-generated randomization to administer either MSC or vehicle placebo control with a 2:1 allocation to the MSC: placebo arm.

Read the detailed description

MSCs are adult, non-hematopoietic precursor cells derived from a variety of tissues (e.g., bone marrow, adipose tissue, and placenta) and have been used as therapy in multiple conditions, especially in immune-mediated inflammatory diseases, such as graft versus-host disease (GVHD) and systemic lupus erythematosus (SLE) with evidence of benefit.

In preclinical models, MSC are effective in ameliorating acute lung injury due to their ability to secrete paracrine factors that regulate lung endothelial and epithelial permeability, including growth factors, anti-inflammatory cytokines, and antimicrobial peptides. Based on the promising pre-clinical preliminary data and intriguing results in patients with COVID-19 associated pneumonia and ARDS as well as an established safety profile of MSC generally and in ARDS in particular, the researchers propose multiple dosing of MSCs as a study treatment to ameliorate the severity and duration of SARS-CoV-2 associated pneumonia and ARDS potentially improve survival.

Patients will receive study agent (MSC or placebo) within 48 hours of enrollment. Three doses will be administered unless a severe infusion adverse event occurs that is related to the MSC infusion. Doses will be repeated approximately every 48-72 hours with the aim of completing 3 doses within 7 days of the first dose. All patients will receive standard of care treatments for ARDS.

02

Conditions studied

  • Acute Respiratory Distress Syndrome
  • ARDS (Moderate or Severe)
  • COVID-19 Pneumonia

Keywords

  • cytokine storm
  • Mesenchymal Stem Cells
  • SARS-CoV-2
  • COVID-19
  • Mesenchymal Stromal Cells
  • MSC
03

In context

COVID-19

7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.

This study's enrollment of 8 is below the median of 100 across 4,099 interventional studies indexed under COVID-19.

Browse COVID-19 studies →

Lead sponsor

Masonic Cancer Center, University of Minnesota is the lead sponsor of 284 studies on the registry; 34 are open to participants now.

Of its 39 completed or terminated interventional studies of FDA-regulated products, 28 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Age 18-80 years
  • Meets 'Berlin Criteria' for diagnosis of moderate to severe ARDS for a minimum of 4 hours
  • Less than 48 hours on a ventilator after meeting criteria for diagnosis of ARDS
  • SARS-CoV-2 (proven by RT-PCR assay) with radiographic infiltrates
  • PaO2/FiO2 \< 250
  • Positive end-expiratory airway pressure (PEEP) >5 cm H20
  • Elevated C-reactive protein (above laboratory upper limit of normal)
  • Meets organ function requirements, including left ventricular ejection fraction (LVEF) >35% ( as defined below)
  • Off other investigational agents directed against inflammatory cytokines 48 hours prior to enrollment; agents directed against the replication of SARS-CoV-2 [e.g., Remdesivir] are permitted
  • Voluntary informed consent in person or virtually by the patient or patient surrogate considering the face to face limitations during the COVID-19 pandemic and, given the nature of the study population, which frequently requires mechanical ventilation with sedation, surrogate consent will likely occur in a substantial proportion of the study population (this will remain a valid consent until the patient is fully alert, and aware, and can provide a second consent to continue participation in the study).

  • Adequate organ function is defined as:

    • Renal: Calculated estimated glomerular filtration rate >30 mL/min/1.73 m2 (on chemistry panel)
    • Hepatic: Bilirubin \<3x upper limit of normal (ULN) and AST, ALT and alkaline phosphatase \<5x ULN
    • Cardiac: Absence of uncontrolled arrhythmia and LVEF >35%

Exclusion criteria

Exclusion Criteria:

  • Ventilator support of FiO2 >0·8 or PEEP >20 cm H2O and ongoing use of more than two vasopressors for 2 or more hours with any agent at doses shown below in the supine position.

    • Norepinephrine >12 μg/min or 0.2 μg/kg per min
    • Phenylephrine >150 μg/min or 3 μg/kg per min
    • Epinephrine >10 ug/min or 0.2 μg/kg per min
    • Vasopressin >0.04 units/min
  • Concurrent use of other investigational agents specifically for treatment of ARDS or inflammatory cytokines. (Note: Agents established to be efficacious and/or those used outside of formal trials are permitted as supportive data emerge)
  • Known ineligibility for use of a ventilator for a minimum of 7 days, as judged by the institution's Triage Team
  • Known allergy to MSC components: fetal calf serum, human albumin or DMSO
  • Active invasive malignant disease requiring chemotherapy/radiation
  • Other concurrent life-threatening disease (life expectancy \<6 months) or eligible for hospice care
  • Known history of HIV infection on active treatment
  • Females who are pregnant or breastfeeding
  • Current mean arterial pressure (MAP) \<60 mmHg while on 2 or more vasopressors at above doses for more than 2 hours
  • History of any significant cardiac (myocardial infarction within 12 months of screening visit or unstable angina), chronic ongoing hepatic, or renal disease (grade 3 or higher); diagnosis of congestive heart failure with hypoxemia primarily due to decompensated heart failure; diagnosis of severe chronic obstructive pulmonary disease (COPD) or interstitial lung disease requiring supplemental oxygen at home
  • Concurrent diagnosis of diffuse alveolar hemorrhage
  • Requiring continuous dialysis (unable to stop dialysis during study agent infusion)
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
8 participants (actual)

Study arms

  • Experimental
    Mesenchymal Stromal Cells

    Three fixed doses of MSC approximately 48 hours apart.

    Biological: Mesenchymal stromal cells

  • Placebo comparator
    Placebo

    Three fixed doses of placebo control approximately 48 hours apart.

    Other: Placebo

Interventions

  • BiologicalMesenchymal stromal cells

    Thawed product containing MSC(300x10\^6) in DMSO resuspended 1:1 with Dextran 40 + 5% human serum albumin \[total volume 60 mL\]

    Also known as: MSC

  • OtherPlacebo

    Dextran 40 + 5% human serum albumin \[total volume 60 mL\]

06

What researchers measure

Primary outcomes

  1. Incidence of Grade 3-5 Infusional Toxicities and Predefined Hemodynamic or Respiratory Adverse Events Related to the Infusion of MSC

    Time frame: Within 6 hours of the start of the infusion

Secondary outcomes

  1. Change in Biomarkers of Inflammation From Day 0 to Day 7

    Mean (SD) represents the change on day 7 after treatment compared to pretreatment value for each biomarker of inflammation. (IL-1, IL-6, IL-8 and TNFa) Measured in pg/mL.

    Time frame: Day 7 after first infusion

  2. Trend Changes in PaO2:FiO2 Ratio

    Trend change was determined by evaluating PaO2:FiO2 ratios at prespecified time points and determining the slope of the line of best fit across data points for each patient, followed by taking the mean and SD across patients in each treatment group. Negative and positive slopes indicating decreasing or increasing values over time, respectively.

    Time frame: On the day of screening and on days 3, 7 and 14 after first infusion

  3. Trend Changes in Mean Airway Pressure

    Trend change was determined by evaluating mean airway pressure values at prespecified time points and determining the slope of the line of best fit across data points for each patient, followed by taking the mean and SD across patients in each treatment group. Negative and positive slopes indicating decreasing or increasing values over time, respectively.

    Time frame: On the day of screening and on days 3, 7 and 14 after first infusion

  4. Trend Changes in Peak Pressure

    Trend change was determined by evaluating peak pressure values at prespecified time points and determining the slope of the line of best fit across data points for each patient, followed by taking the mean and SD across patients in each treatment group. Negative and positive slopes indicating decreasing or increasing values over time, respectively.

    Time frame: On the day of screening and on days 3, 7 and 14 after first infusion

  5. Trend Changes in Plateau Pressure

    Trend change was determined by evaluating plateau pressure values at prespecified time points and determining the slope of the line of best fit across data points for each patient, followed by taking the mean and SD across patients in each treatment group. Negative and positive slopes indicating decreasing or increasing values over time, respectively.

    Time frame: On the day of screening (baseline) and on days 3, 7 and 14 after first infusion

  6. Trend Changes in Positive End-expiratory Airway Pressure (PEEP)

    Trend change was determined by evaluating Positive end-expiratory airway pressure (PEEP) values at prespecified time points and determining the slope of the line of best fit across data points for each patient, followed by taking the mean and SD across patients in each treatment group. Negative and positive slopes indicating decreasing or increasing values over time, respectively.

    Time frame: On the day of screening and on days 3, 7 and 14 after first infusion

  7. Incidence of Mortality

    Time frame: 50 days after first infusion

  8. Number of ICU-free Days

    Time frame: 28 days after first infusion

  9. Number of Days Alive and Ventilator Free

    Time frame: 28 days after first infusion

  10. Change in Acute Lung Injury (ALI) Score 2

    Acute Lung Injury Score is a composite 4 point scoring system validated by the NHLBI ARDS Network that considers PaO2/FiO2, the level of positive end-expiratory airway pressure, respiratory compliance, and the extent of pulmonary infiltrates on the chest radiograph. Each criterion is scored from 0-4 based on the severity of the condition. The final score is calculated by dividing the total score by the number of criteria used. A score of 0 indicates no lung injury, and a score over 2.5 indicates Acute respiratory distress syndrome (ARDS). The scoring ranges from 0 to a maximum score of 3.

    Time frame: Baseline and Day 28 after first infusion

  11. Incidence of Serious Adverse Events

    Time frame: 28 days after first infusion

  12. Number of Days Alive Off Supplemental Oxygen

    Time frame: 100 days after first infusion

07

Results

Posted Oct 1, 2024

Participant flow

Participant flow — Overall Study
MilestoneMesenchymal Stromal CellsPlacebo
Started62
Completed30
Not completed32

Outcome measures

PrimaryIncidence of Grade 3-5 Infusional Toxicities and Predefined Hemodynamic or Respiratory Adverse Events Related to the Infusion of MSC
Time frame:
Within 6 hours of the start of the infusion
Reported as:
Count of participants · Participants
Incidence of Grade 3-5 Infusional Toxicities and Predefined Hemodynamic or Respiratory Adverse Events Related to the Infusion of MSC
ParticipantsMesenchymal Stromal CellsPlacebo
Incidence of Grade 3-5 Infusional Toxicities and Predefined Hemodynamic or Respiratory Adverse Events Related to the Infusion of MSC00
SecondaryChange in Biomarkers of Inflammation From Day 0 to Day 7

Mean (SD) represents the change on day 7 after treatment compared to pretreatment value for each biomarker of inflammation. (IL-1, IL-6, IL-8 and TNFa) Measured in pg/mL.

Time frame:
Day 7 after first infusion
Reported as:
Mean · pg/mL
Change in Biomarkers of Inflammation From Day 0 to Day 7
pg/mLMesenchymal Stromal CellsPlacebo
Change in IL-10 ± 0.550.4 ± 0.99
Change in IL-6-61 ± 190102 ± 75
Change in TNFa0 ± 122 ± 2
Change in IL-86 ± 53145 ± 33
SecondaryTrend Changes in PaO2:FiO2 Ratio

Trend change was determined by evaluating PaO2:FiO2 ratios at prespecified time points and determining the slope of the line of best fit across data points for each patient, followed by taking the mean and SD across patients in each treatment group. Negative and positive slopes indicating decreasing or increasing values over time, respectively.

Time frame:
On the day of screening and on days 3, 7 and 14 after first infusion
Reported as:
Mean · ratio/day
Trend Changes in PaO2:FiO2 Ratio
ratio/dayMesenchymal Stromal CellsPlacebo
Trend Changes in PaO2:FiO2 Ratio-7 ± 88 ± 7
SecondaryTrend Changes in Mean Airway Pressure

Trend change was determined by evaluating mean airway pressure values at prespecified time points and determining the slope of the line of best fit across data points for each patient, followed by taking the mean and SD across patients in each treatment group. Negative and positive slopes indicating decreasing or increasing values over time, respectively.

Time frame:
On the day of screening and on days 3, 7 and 14 after first infusion
Reported as:
Mean · ratio/day
Trend Changes in Mean Airway Pressure
ratio/dayMesenchymal Stromal CellsPlacebo
Trend Changes in Mean Airway Pressure-2.7 ± 60.3 ± 0.4
SecondaryTrend Changes in Peak Pressure

Trend change was determined by evaluating peak pressure values at prespecified time points and determining the slope of the line of best fit across data points for each patient, followed by taking the mean and SD across patients in each treatment group. Negative and positive slopes indicating decreasing or increasing values over time, respectively.

Time frame:
On the day of screening and on days 3, 7 and 14 after first infusion
Reported as:
Mean · ratio/day
Trend Changes in Peak Pressure
ratio/dayMesenchymal Stromal CellsPlacebo
Trend Changes in Peak Pressure-0.28 ± 1.510.19 ± 0.45
SecondaryTrend Changes in Plateau Pressure

Trend change was determined by evaluating plateau pressure values at prespecified time points and determining the slope of the line of best fit across data points for each patient, followed by taking the mean and SD across patients in each treatment group. Negative and positive slopes indicating decreasing or increasing values over time, respectively.

Time frame:
On the day of screening (baseline) and on days 3, 7 and 14 after first infusion
Reported as:
Mean · ratio/day
Trend Changes in Plateau Pressure
ratio/dayMesenchymal Stromal CellsPlacebo
Trend Changes in Plateau Pressure0.08 ± 2.910.38 ± 0.71
SecondaryTrend Changes in Positive End-expiratory Airway Pressure (PEEP)

Trend change was determined by evaluating Positive end-expiratory airway pressure (PEEP) values at prespecified time points and determining the slope of the line of best fit across data points for each patient, followed by taking the mean and SD across patients in each treatment group. Negative and positive slopes indicating decreasing or increasing values over time, respectively.

Time frame:
On the day of screening and on days 3, 7 and 14 after first infusion
Reported as:
Mean · ratio/day
Trend Changes in Positive End-expiratory Airway Pressure (PEEP)
ratio/dayMesenchymal Stromal CellsPlacebo
Trend Changes in Positive End-expiratory Airway Pressure (PEEP)-0.68 ± 0.900.14 ± 0.28
SecondaryIncidence of Mortality
Time frame:
50 days after first infusion
Reported as:
Count of participants · Participants
Incidence of Mortality
ParticipantsMesenchymal Stromal CellsPlacebo
Incidence of Mortality21
SecondaryNumber of ICU-free Days
Time frame:
28 days after first infusion
Reported as:
Count of participants · Participants
Number of ICU-free Days
ParticipantsMesenchymal Stromal CellsPlacebo
0 days32
7 days10
18 days10
22 days10
SecondaryNumber of Days Alive and Ventilator Free
Time frame:
28 days after first infusion
Reported as:
Count of participants · Participants
Number of Days Alive and Ventilator Free
ParticipantsMesenchymal Stromal CellsPlacebo
0 days31
1 day01
4 days10
23 days10
24 days10
SecondaryChange in Acute Lung Injury (ALI) Score 2

Acute Lung Injury Score is a composite 4 point scoring system validated by the NHLBI ARDS Network that considers PaO2/FiO2, the level of positive end-expiratory airway pressure, respiratory compliance, and the extent of pulmonary infiltrates on the chest radiograph. Each criterion is scored from 0-4 based on the severity of the condition. The final score is calculated by dividing the total score by the number of criteria used. A score of 0 indicates no lung injury, and a score over 2.5 indicates Acute respiratory distress syndrome (ARDS). The scoring ranges from 0 to a maximum score of 3.

Time frame:
Baseline and Day 28 after first infusion
Reported as:
Mean · Scores on a scale
Change in Acute Lung Injury (ALI) Score 2
Scores on a scaleMesenchymal Stromal CellsPlacebo
Change in Acute Lung Injury (ALI) Score 2-0.25 ± 0.43-1.5 ± 0
SecondaryIncidence of Serious Adverse Events
Time frame:
28 days after first infusion
Reported as:
Number · Participants
Incidence of Serious Adverse Events
ParticipantsMesenchymal Stromal CellsPlacebo
Incidence of Serious Adverse Events21
SecondaryNumber of Days Alive Off Supplemental Oxygen
Time frame:
100 days after first infusion
Reported as:
Count of participants · Participants
Number of Days Alive Off Supplemental Oxygen
ParticipantsMesenchymal Stromal CellsPlacebo
0 days21
10 days10
53 days01
61 days10
87 days10
88 days10

Adverse events

Collected over 6 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Mesenchymal Stromal Cells2/6 (33.3%)2/6 (33.3%)6/6 (100%)
Placebo1/2 (50%)1/2 (50%)2/2 (100%)
Most frequent serious events
Most frequent serious events
EventMesenchymal Stromal CellsPlacebo
Adult respiratory distress syndromeRespiratory, thoracic and mediastinal disorders1/61/2
Lung infectionInfections and infestations1/60/2
Most frequent other events
Showing 10 of 37
Most frequent other events
EventMesenchymal Stromal CellsPlacebo
AnemiaBlood and lymphatic system disorders4/62/2
AcidosisMetabolism and nutrition disorders0/62/2
HyperkalemiaMetabolism and nutrition disorders1/61/2
HypernatremiaMetabolism and nutrition disorders1/61/2
HypocalcemiaMetabolism and nutrition disorders1/61/2
HypoalbuminemiaMetabolism and nutrition disorders0/61/2
BacteremiaInfections and infestations2/61/2
Bronchial infectionInfections and infestations1/61/2
Investigations - Other, specifyInvestigations3/60/2
Aspartate aminotransferase increasedInvestigations2/61/2

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Mesenchymal Stromal CellsPlaceboTotal
<=18 years000
Between 18 and 65 years314
>=65 years314
Sex: Female, Male
Sex: Female, Male(Participants)Mesenchymal Stromal CellsPlaceboTotal
Female112
Male516
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Mesenchymal Stromal CellsPlaceboTotal
Hispanic or Latino000
Not Hispanic or Latino628
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Mesenchymal Stromal CellsPlaceboTotal
American Indian or Alaska Native000
Asian011
Native Hawaiian or Other Pacific Islander000
Black or African American101
White516
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Mesenchymal Stromal CellsPlaceboTotal
United States628
08

Study locations

2 sites
  • University of Minnesota
    Minneapolis, Minnesota 55455, United States
  • University of Pittsburgh
    Pittsburgh, Pennsylvania 15261, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Oct 21, 2020
  • Informed consent form · Jul 9, 2020

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 29, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04466098
Lead sponsor
Masonic Cancer Center, University of Minnesota
Responsible party
Sponsor
First posted
Jul 10, 2020
Start date
Jul 30, 2020
Primary completion
Feb 25, 2022
Completion
Dec 31, 2024
Results posted
Oct 1, 2024
Last update
Jan 29, 2025

Study contacts

David Ingbar, MD
principal investigator · Masonic Cancer Center, University of Minnesota

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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