Acute Respiratory Distress SyndromePhase 2NCT04466098
Multiple Dosing of Mesenchymal Stromal Cells in Patients With ARDS (COVID-19)
A Phase 2 study testing Mesenchymal stromal cells in people with Acute Respiratory Distress Syndrome and ARDS (Moderate or Severe), run by Masonic Cancer Center, University of Minnesota at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Respiratory Distress Syndrome, ARDS (Moderate or Severe), COVID-19 Pneumonia
- What is being tested?
- Mesenchymal stromal cells
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 2 sitesUnited States
- Study dates
- 30 Jul 2020to 31 Dec 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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%
Who cannot join
- 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)
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- 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)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Minnesota
Minneapolis, Minnesota, 55455
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261
About this study
Official title: Multi-center, Randomized, Placebo Controlled, Interventional Phase 2A Clinical Trial Evaluating the Safety and Potential Efficacy of Multiple Dosing of Mesenchymal Stromal Cells in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2)
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.
- Being tested
- Mesenchymal stromal cells, Placebo
- Keywords
- cytokine storm, Mesenchymal Stem Cells, SARS-CoV-2, COVID-19, Mesenchymal Stromal Cells, MSC
- Medical subject headings
- Respiratory Distress Syndrome, Lymphoma, Follicular, Cytokine Release Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymal stromal cellsBiological
Also called MSC
Thawed product containing MSC(300x10^6) in DMSO resuspended 1:1 with Dextran 40 + 5% human serum albumin [total volume 60 mL]
PlaceboOther
Dextran 40 + 5% human serum albumin [total volume 60 mL]
| Study group | Role | What they receive |
|---|---|---|
| Mesenchymal Stromal Cells | Experimental | Three fixed doses of MSC approximately 48 hours apart. Receives: Biological: Mesenchymal stromal cells |
| Placebo | Placebo comparator | Three fixed doses of placebo control approximately 48 hours apart. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Grade 3-5 Infusional Toxicities and Predefined Hemodynamic or Respiratory Adverse Events Related to the Infusion of MSC
Measured: Within 6 hours of the start of the infusion
Secondary outcomes (12)
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.
Measured: Day 7 after first infusion
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.
Measured: On the day of screening and on days 3, 7 and 14 after first infusion
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.
Measured: On the day of screening and on days 3, 7 and 14 after first infusion
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.
Measured: On the day of screening and on days 3, 7 and 14 after first infusion
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.
Measured: On the day of screening (baseline) and on days 3, 7 and 14 after first infusion
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.
Measured: On the day of screening and on days 3, 7 and 14 after first infusion
Incidence of Mortality
Measured: 50 days after first infusion
Number of ICU-free Days
Measured: 28 days after first infusion
Number of Days Alive and Ventilator Free
Measured: 28 days after first infusion
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.
Measured: Baseline and Day 28 after first infusion
Incidence of Serious Adverse Events
Measured: 28 days after first infusion
Number of Days Alive Off Supplemental Oxygen
Measured: 100 days after first infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2020
- Study start30 Jul 2020
- Primary completion25 Feb 2022
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized (2:1 ratio) placebo controlled trial.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Ingbar, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04466098
- Sponsor's protocol ID
- 2020LS075
- Other IDs
- MT2020-12
- Status last verified
- Jan 2025
- First submitted
- 8 Jul 2020
- Last updated
- 29 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-center, Randomized, Placebo Controlled, Interventional Phase 2A Clinical Trial Evaluating the Safety and Potential Efficacy of Multiple Dosing of Mesenchymal Stromal Cells in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2)
- ClinicalTrials.gov ID
- NCT04466098
- Acronym / sponsor ID
- 2020LS075
- Keywords
- cytokine storm, Mesenchymal Stem Cells, SARS-CoV-2, COVID-19, Mesenchymal Stromal Cells, MSC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- 30 Jul 2020 (actual)
- Primary completion
- 25 Feb 2022 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 10 Jul 2020 (actual)
- Results
- Posted 1 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- This is a randomized (2:1 ratio) placebo controlled trial.
| Arm | Type | Receives |
|---|---|---|
| Mesenchymal Stromal Cells | Experimental | Biological: Mesenchymal stromal cellsThree fixed doses of MSC approximately 48 hours apart. |
| Placebo | Placebo comparator | Other: PlaceboThree fixed doses of placebo control approximately 48 hours apart. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (16 listed)
- 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.
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mesenchymal stromal cellsAlso: MSCThawed product containing MSC(300x10^6) in DMSO resuspended 1:1 with Dextran 40 + 5% human serum albumin [total volume 60 mL] | Biological | Mesenchymal Stromal Cells |
| PlaceboDextran 40 + 5% human serum albumin [total volume 60 mL] | Other | Placebo |
Primary outcome
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
12 secondary outcomes
Change in Biomarkers of Inflammation From Day 0 to Day 7
Time frame: Day 7 after first infusion
Trend Changes in PaO2:FiO2 Ratio
Time frame: On the day of screening and on days 3, 7 and 14 after first infusion
Trend Changes in Mean Airway Pressure
Time frame: On the day of screening and on days 3, 7 and 14 after first infusion
Trend Changes in Peak Pressure
Time frame: On the day of screening and on days 3, 7 and 14 after first infusion
Trend Changes in Plateau Pressure
Time frame: On the day of screening (baseline) and on days 3, 7 and 14 after first infusion
Trend Changes in Positive End-expiratory Airway Pressure (PEEP)
Time frame: On the day of screening and on days 3, 7 and 14 after first infusion
Incidence of Mortality
Time frame: 50 days after first infusion
Number of ICU-free Days
Time frame: 28 days after first infusion
Number of Days Alive and Ventilator Free
Time frame: 28 days after first infusion
Change in Acute Lung Injury (ALI) Score 2
Time frame: Baseline and Day 28 after first infusion
Incidence of Serious Adverse Events
Time frame: 28 days after first infusion
Number of Days Alive Off Supplemental Oxygen
Time frame: 100 days after first infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Ingbar, MD principal investigator
Masonic Cancer Center, University of Minnesota
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mesenchymal stromal cells in people with Acute Respiratory Distress Syndrome and ARDS (Moderate or Severe), run by Masonic Cancer Center, University of Minnesota at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2025.