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Completed

NCT Number: NCT04355728

Use of UC-MSCs for COVID-19 Patients

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).

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Key information

Conditions

Corona Virus Infection ARDS ARDS, Human Acute Respiratory Distress Syndrome COVID-19 Coronaviridae Infections Coronavirus Infections Infections Lung Diseases Nidovirales Infections Pneumonia Pneumonia, Viral RNA Virus Infections Respiration Disorders Respiratory Distress Syndrome Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Diabetes Research Institute, University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • 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
  • 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

Treatment and study plan

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 care

Other

Best supportive care treatment per the treating hospital protocol.

Primary outcomes

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

    Time frame: 6 and 24 hours

    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:

    • 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
    • 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%.
    • In patients receiving high flow oxygen therapy: worsening hypoxemia, as indicated by requirement of intubation and mechanical ventilation.
    • New cardiac arrhythmia requiring cardioversion
    • New ventricular tachycardia, ventricular fibrillation, or asystole
    • A clinical scenario consistent with transfusion incompatibility or transfusion-related infection
    • Cardiac arrest or death within 24h post infusion

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

    Time frame: 31 days

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

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

    Time frame: 90 days

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

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

    Time frame: 90 days

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

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

    Time frame: 90 days

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

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

    Time frame: 90 days

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

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

    Time frame: 90 days

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

  8. Subjects With Adverse Events by Relatedness to Treatment

    Time frame: 90 days

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

Secondary outcomes

  1. Survival at 31 Days Post First Infusion

    Time frame: 31 Days

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

  2. Survival at 60 Days Post First Infusion

    Time frame: 60 days

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

  3. Time to Recovery

    Time frame: 31 days

    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.

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

    Time frame: 28 days post second infusion

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

  5. Ventilator-Free Days Throughout 90 Days

    Time frame: 90 days or hospital discharge, whichever is earlier

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

  6. Respiratory Rate and Oxygenation Index (ROX Index)

    Time frame: day 6

    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.

  7. Oxygenation Index (OI)

    Time frame: day 6

    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).

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

    Time frame: day 6

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

  9. Sequential Organ Failure Assessment (SOFA) Scores

    Time frame: Day 6

    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).

  10. Smell Identification Test (SIT) Scores

    Time frame: 90 days

    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

  11. White Blood Cell Count (WBC)

    Time frame: day 6

    As assessed via serum blood samples.

  12. Platelets Count

    Time frame: day 6

    As assessed via serum blood samples.

  13. Hemogoblin

    Time frame: day 6

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

  14. Hematocrit

    Time frame: day 6

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

  15. Neutrophils

    Time frame: day 6

    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

  16. Lymphocytes

    Time frame: day 6

    Lymphocyte count as assessed via serum blood samples

  17. Glomerular Filtration Rate

    Time frame: day 6

    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.

  18. Total Protein

    Time frame: Day 6

    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.

  19. Sodium

    Time frame: day 6

    Sodium levels as assessed by serum blood samples.

  20. Potassium

    Time frame: day 6

    Potassium levels as assessed via serum blood samples.

  21. Creatinine

    Time frame: day 6

    Creatinine levels as assessed via serum blood samples

  22. Glucose

    Time frame: day 6

    Glucose levels as assessed via serum blood samples

  23. Albumin

    Time frame: day 6

    Albumin levels as assessed via serum blood samples

  24. Alkaline Phosphatase

    Time frame: day 6

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

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

    Time frame: day 6

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

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

    Time frame: day 6

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

  27. Total Bilirubin

    Time frame: day 6

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

  28. Blood Urea Nitrogen (BUN)

    Time frame: day 6

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

  29. Calcium

    Time frame: day 6

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

  30. Chloride

    Time frame: day 6

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

  31. Carbon Dioxide (CO2)

    Time frame: day 6

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

  32. C-Reactive Protein Levels

    Time frame: day 6

    As assessed via serum blood samples.

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

    Time frame: day 6

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

  34. D-dimer Levels

    Time frame: day 6

    As assessed via serum blood samples.

  35. 25-Hydroxy Vitamin D Levels

    Time frame: day 6

    As assessed via serum blood samples.

  36. Tumor Necrosis Factor-alpha (TNFα)

    Time frame: day 6

    Analysis of TNFα in peripheral blood plasma

  37. Tumor Necrosis Factor-beta (TNFβ)

    Time frame: day 6

    Analysis of TNFβ in peripheral blood plasma

  38. Soluble Tumor Necrosis Factor Receptor 2 (sTNFR2)

    Time frame: day 6

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

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

    Time frame: day 6

    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).

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

    Time frame: 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.

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

    Time frame: day 6

    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.

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

    Time frame: day 14

    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.

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

    Time frame: day 14 post first infusion

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

Sponsors and collaborators

Lead sponsor

Camillo Ricordi

Other

Registry information

Official study title

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

Important dates

Study start
2020
Primary completion
2020
Study completion
2020
First posted
Apr 21, 2020
Registry last updated
Dec 6, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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