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Corona Virus InfectionPhase 1/2NCT04355728

Use of UC-MSCs for COVID-19 Patients

A Phase 1/2 study of Corona Virus Infection and ARDS, run by Camillo Ricordi at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this research study is to learn about the safety and efficacy of human umbilical cord derived Mesenchymal Stem Cells (UC-MSC) for treatment of COVID-19 Patients with Severe Complications of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Corona Virus Infection, ARDS, ARDS, Human
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
24 participants
Where
1 siteUnited States
Study dates
25 Apr 2020to 31 Oct 2020
Phase
Phase 1/2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients >/= 18 years old diagnosed with COVID-19 (as evaluated by PCR test confirming infection with SARS-CoV-2) will be eligible for inclusion if they meet all of the below criteria. Inclusion criteria must all be present within a 24-hour time period at the time of enrollment:
  • Patient currently hospitalized
  • Aged ≥ 18 years
  • Willing and able to provide written informed consent, or with a legal representative who can provide informed consent
  • Peripheral capillary oxygen saturation (SpO2) ≤ 94% at room air, or requiring supplemental oxygen at screening
  • PaO2/FiO2 ratio < 300 mmHg
  • Bilateral infiltrates on frontal chest radiograph or bilateral ground glass opacities on a chest CT scan
  • Hypoxemia requiring an increase in the fraction of inspired oxygen (FiO2) of ≥ 20% AND an increase in positive end-expiratory airway pressure (PEEP) level of 5 cm H2O or more to maintain transcutaneous oxygen saturations in the target range of 88-95%, or requirement for escalation from oxygen therapy to invasive mechanical ventilation

Who cannot join

  • PaO2/FiO2 ≥ 300 at the time of enrollment
  • A previous MSC infusion not related to this trial
  • History of Pulmonary Hypertension (WHO Class III/IV)
  • History of left atrial hypertension or decompensated left heart failure.
  • Pregnant or lactating patient
  • Unstable arrhythmia
Show all 15Show fewer
  • Patients with previous lung transplant
  • Patients currently receiving chronic dialysis
  • Patients currently receiving Extracorporeal Membrane Oxygenation (ECMO)
  • Presence of any active malignancy (except non-melanoma skin cancer)
  • Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
  • Moderate to severe liver disease (AST and ALT >5 X ULN)
  • Severe chronic respiratory disease with a PaCO2 > 50 mm Hg or the use of home oxygen
  • Baseline QT prolongation
  • Moribund patient not expected to survive > 24 hours

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Diabetes Research Institute, University of Miami Miller School of Medicine

    Miami, Florida, 33136

Other trials in United States

About this study

Official title: Umbilical Cord-derived Mesenchymal Stem Cells for COVID-19 Patients With Acute Respiratory Distress Syndrome (ARDS)

The purpose of this research study is to learn about the safety and efficacy of human umbilical cord derived Mesenchymal Stem Cells (UC-MSC) for treatment of COVID-19 Patients with Severe Complications of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS).

Being tested
Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care., Vehicle + Heparin along with best supportive care
Keywords
COVID-19
Medical subject headings
Coronavirus Infections, Respiratory Distress Syndrome, COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.Biological

    UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.

  • Vehicle + Heparin along with best supportive careOther

    Best supportive care treatment per the treating hospital protocol.

Study groups in NCT04355728
Study groupRoleWhat they receive
UC-MSCs GroupExperimentalParticipants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment.
Receives: Biological: Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.
Control GroupPlacebo comparatorParticipants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment.
Receives: Other: Vehicle + Heparin along with best supportive care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Pre-Specified Infusion Associated Adverse Events

    Safety as defined by the number of pre-specified infusion associated adverse events as assessed by treating physician. Any of the following occurring within 6 h post each infusion:

    1. An increase in vasopressor dose greater than or equal to the following:
    • Norepinephrine: 10 μg/min
    • Phenylephrine: 100 μg/min
    • Dopamine: 10 μg/kg/min
    • Epinephrine: 10 μg/min
    1. In patients receiving mechanical ventilation: worsening hypoxemia, as assessed by a requirement for an increase of PEEP by 5 cm H2O over baseline, or requirement to increase FiO2 of >20%.
    2. In patients receiving high flow oxygen therapy: worsening hypoxemia, as indicated by requirement of intubation and mechanical ventilation.
    3. New cardiac arrhythmia requiring cardioversion
    4. New ventricular tachycardia, ventricular fibrillation, or asystole
    5. A clinical scenario consistent with transfusion incompatibility or transfusion-related infection
    6. Cardiac arrest or death within 24h post infusion

    Measured: 6 and 24 hours

  2. Number of Subjects With Serious Adverse Events by 31 Days After First Infusion

    The number of subjects experiencing serious adverse events by 31 days after the first infusion (corresponding to 28 days after the last infusion).

    Measured: 31 days

  3. Percentage of Participants Experiencing Serious Adverse Events (SAEs) Through Study Day 90

    Safety will be reported as the percentage of participants experiencing serious adverse events through Day 90 as assessed by treating physician.

    Measured: 90 days

  4. Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Total number of adverse events and serious adverse events as assessed by treating physician

    Measured: 90 days

  5. Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) by Severity

    Total number of adverse events plus serious adverse events categorized by severity.

    Measured: 90 days

  6. Subjects With Adverse Events and Serious Adverse Events by Severity

    Total number of subjects with adverse events and serious adverse events categorized by severity.

    Measured: 90 days

  7. Number of Adverse Events and Serious Adverse Events by Relatedness to Treatment

    Total number of adverse events and serious adverse events categorized by relatedness to treatment defined by a medical professional.

    Measured: 90 days

  8. Subjects With Adverse Events by Relatedness to Treatment

    Total number of subjects with adverse events categorized by relatedness to treatment by a medical professional

    Measured: 90 days

Secondary outcomes (43)
  1. Survival at 31 Days Post First Infusion

    Number of participants that are alive at 31 days post first infusion follow up corresponding to 28 day post second infusion.

    Measured: 31 Days

  2. Survival at 60 Days Post First Infusion

    Number of participants alive at 60 days post first infusion follow up.

    Measured: 60 days

  3. Time to Recovery

    Time to discharge or, if the subject was hospitalized, no longer requiring supplemental oxygen and no longer requiring COVID-19-related medical care by 31 days. The numbers represent days at which 25%, 50%, 75% subjects within the treatment group had recovered.

    Measured: 31 days

  4. Ventilator-Free Days Throughout 28 Days Post Second Infusion

    Number of days participants were off ventilators during 28 days post second infusion.

    Measured: 28 days post second infusion

  5. Ventilator-Free Days Throughout 90 Days

    Number of days participants were off ventilators within up to 90 days of hospitalization.

    Measured: 90 days or hospital discharge, whichever is earlier

  6. Respiratory Rate and Oxygenation Index (ROX Index)

    Respiratory Rate-Oxygenation (ROX) index is defined as the ratio of oxygen saturation as measured by pulse oximetry (SpO2)/ Fraction of inspired oxygen (FiO2) to respiratory rate. This index can be used in the assessment of disease progression and the risk of intubation in COVID-19 patients with pneumonia.

    Measured: day 6

  7. Oxygenation Index (OI)

    Measure of the fraction of inspired oxygen (FiO2) and its usage within the body during intensive care, measured using fNIRS (Functional Near Infrared Spectroscopy). The calculation for Oxygenation index is ((FIO2 * Mean airway pressure)/partial pressure of oxygen).

    Measured: day 6

  8. Positive End-Expiratory Pressure (PEEP) and Plateau Pressure (Pplat)

    Measuring the respiratory mechanics; positive end-expiratory pressure (PEEP) and plateau pressure (Pplat) in ventilated patients visit 8 (day 6)

    Measured: day 6

  9. Sequential Organ Failure Assessment (SOFA) Scores

    Sequential Organ Failure Assessment (SOFA) Scores is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from a minimum of 0 (normal) to a maximum of 4 (high degree of dysfunction/failure). The total score corresponds to the sum of the six different scores of the organ systems. In total, the minimum SOFA score is 0 (normal) and the maximum SOFA score is 24 (highest degree dysfunction/failure).

    Measured: Day 6

  10. Smell Identification Test (SIT) Scores

    SIT measures the participant's sense of smell. SIT has a total score ranging from 0 to 40 with the higher the score indicating a more normal sense of smell

    Measured: 90 days

  11. White Blood Cell Count (WBC)

    As assessed via serum blood samples.

    Measured: day 6

  12. Platelets Count

    As assessed via serum blood samples.

    Measured: day 6

  13. Hemogoblin

    Measures the total amount of the oxygen-carrying protein in the blood as assessed via serum blood samples.

    Measured: day 6

  14. Hematocrit

    The percentage by volume of red cells in your blood as assessed via serum blood samples.

    Measured: day 6

  15. Neutrophils

    the amount of immune cells (that is one of the first cell types to travel to the site of an infection) as assessed via serum blood samples

    Measured: day 6

  16. Lymphocytes

    Lymphocyte count as assessed via serum blood samples

    Measured: day 6

  17. Glomerular Filtration Rate

    Glomerular filtration rate (GFR) as assessed via serum blood samples to check how well the kidneys are working. It estimates how much blood passes through the glomeruli each minute.

    Measured: day 6

  18. Total Protein

    Total protein as assessed via serum blood samples as a part of the comprehensive metabolic panel (CMP). It is a measurement of the sum of albumin and globulins.

    Measured: Day 6

  19. Sodium

    Sodium levels as assessed by serum blood samples.

    Measured: day 6

  20. Potassium

    Potassium levels as assessed via serum blood samples.

    Measured: day 6

  21. Creatinine

    Creatinine levels as assessed via serum blood samples

    Measured: day 6

  22. Glucose

    Glucose levels as assessed via serum blood samples

    Measured: day 6

  23. Albumin

    Albumin levels as assessed via serum blood samples

    Measured: day 6

  24. Alkaline Phosphatase

    Alkaline phosphatase levels as assessed via serum blood samples for the Comprehensive Metabolic Panel.

    Measured: day 6

  25. Alanine Aminotransferase or Serum Glutamate-pyruvate Transaminase (ALT or SGPT)

    The alanine aminotransferase or serum glutamate-pyruvate transaminase (ALT or SGPT) test as assessed via serum blood samples

    Measured: day 6

  26. Aspartate Aminotransferase or Serum Glutamic Oxaloacetic Transaminase (AST or SGOT)

    The aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST or SGOT) test as assessed via serum blood samples

    Measured: day 6

  27. Total Bilirubin

    Bilirubin levels as assessed via serum blood samples for the comprehensive metabolic panel.

    Measured: day 6

  28. Blood Urea Nitrogen (BUN)

    Blood urea nitrogen (BUN) levels as assessed via serum blood samples for the comprehensive metabolic panel.

    Measured: day 6

  29. Calcium

    Calcium levels as assessed via serum blood samples for the comprehensive metabolic panel.

    Measured: day 6

  30. Chloride

    Chloride levels as assessed via serum blood samples for the comprehensive metabolic panel.

    Measured: day 6

  31. Carbon Dioxide (CO2)

    Carbon Dioxide (CO2) levels as assessed via serum blood samples for the comprehensive metabolic panel.

    Measured: day 6

  32. C-Reactive Protein Levels

    As assessed via serum blood samples.

    Measured: day 6

  33. Arachidonic Acid/Eicosapentaenoic Acid (AA/EPA) Ratio

    As assessed via serum blood samples on day 6 (visit 8).

    Measured: day 6

  34. D-dimer Levels

    As assessed via serum blood samples.

    Measured: day 6

  35. 25-Hydroxy Vitamin D Levels

    As assessed via serum blood samples.

    Measured: day 6

  36. Tumor Necrosis Factor-alpha (TNFα)

    Analysis of TNFα in peripheral blood plasma

    Measured: day 6

  37. Tumor Necrosis Factor-beta (TNFβ)

    Analysis of TNFβ in peripheral blood plasma

    Measured: day 6

  38. Soluble Tumor Necrosis Factor Receptor 2 (sTNFR2)

    Analysis of soluble tumor necrosis factor receptor 2 (sTNFR2) in peripheral blood plasma

    Measured: day 6

  39. Viral Load by SARS-CoV-2 RT-PCR

    Viral load as assessed in blood plasma for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) via Reverse Transcriptase Polymerase Chain Reaction (RT-PCR).

    Measured: day 6

  40. Number of Participants Reporting Panel Reactive Antibody (PRA) Positivity at Day 3 Post First Infusion

    Number of participants reporting panel reactive antibody (PRA) positivity at Day 3 post first infusion for class I and class II as assessed via serum blood samples. These antibodies can develop following a transplant. Recipients can become sensitized to certain molecules (Human Leukocyte Antigen Class I or Class II), which can affect immune responses to and rejection of potential future transplants.

    Measured: day 3 post first infusion

  41. Number of Participants Reporting Panel Reactive Antibody (PRA) Positivity at Day 6 Post First Infusion

    Number of participants reporting panel reactive antibody (PRA) positivity at Day 6 post first infusion for class I and class II as assessed via serum blood samples. These antibodies can develop following a transplant. Recipients can become sensitized to certain molecules (Human Leukocyte Antigen Class I or Class II), which can affect immune responses to and rejection of potential future transplants.

    Measured: day 6

  42. Number of Participants Reporting Panel Reactive Antibody (PRA) Positivity at Day 14 Post First Infusion

    Number of participants reporting panel reactive antibody (PRA) positivity at Day 14 post first infusion for class I and class II as assessed via serum blood samples. These antibodies can develop following a transplant. Recipients can become sensitized to certain molecules (Human Leukocyte Antigen Class I or Class II), which can affect immune responses to and rejection of potential future transplants.

    Measured: day 14

  43. Number of Participants With Positive, Negative, or Borderline Serology Testing for SARS-CoV-2 IgM/IgG

    Number of participants with positive, negative, or borderline SARS-CoV-2 Immunoglobulin M (IgM)/Immunoglobulin G (IgG) serology from serum blood samples.

    Measured: day 14 post first infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Apr 2020
  2. Study start25 Apr 2020
  3. Primary completion31 Oct 2020
  4. Study completion31 Oct 2020

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
The trial has two groups, each with 12 subjects (n=24). All eligible subjects will be randomized to either the treatment group or standard of care, and randomization will be stratified by ARDS severity.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04355728
Sponsor's protocol ID
20200671
Other IDs
20200370
Status last verified
Dec 2021
First submitted
13 Apr 2020
Last updated
6 Dec 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study of Corona Virus Infection and ARDS, run by Camillo Ricordi at 1 site 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 8 inclusion and 15 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 6 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 6 Dec 2021). 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?

Number of Participants With Pre-Specified Infusion Associated Adverse Events (time frame: 6 and 24 hours). The study lists 8 primary outcomes in all. 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 6 Dec 2021.

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