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Use of UC-MSCs for COVID-19 Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04355728
Recruitment Status : Completed
First Posted : April 21, 2020
Results First Posted : December 6, 2021
Last Update Posted : December 6, 2021
Sponsor:
Information provided by (Responsible Party):
Camillo Ricordi, University of Miami

Tracking Information
First Submitted Date  ICMJE April 13, 2020
First Posted Date  ICMJE April 21, 2020
Results First Submitted Date  ICMJE October 15, 2021
Results First Posted Date  ICMJE December 6, 2021
Last Update Posted Date December 6, 2021
Actual Study Start Date  ICMJE April 25, 2020
Actual Primary Completion Date October 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 17, 2021)
  • 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:
    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
    2. 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%.
    3. In patients receiving high flow oxygen therapy: worsening hypoxemia, as indicated by requirement of intubation and mechanical ventilation.
    4. New cardiac arrhythmia requiring cardioversion
    5. New ventricular tachycardia, ventricular fibrillation, or asystole
    6. A clinical scenario consistent with transfusion incompatibility or transfusion-related infection
    7. Cardiac arrest or death within 24h post infusion
  • 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).
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: April 17, 2020)
  • Incidence of pre-specified infusion associated adverse events [ Time Frame: Day 5 ]
    Safety will be defined by the incidence of pre-specified infusion associated adverse events as assessed by treating physician
  • Incidence of Severe Adverse Events [ Time Frame: 90 days ]
    Safety will be defined by the incidence of severe adverse events as assessed by treating physician
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2021)
  • 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.
  • Survival at 60 Days Post First Infusion [ Time Frame: 60 days ]
    Number of participants alive at 60 days post first infusion follow up.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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)
  • 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).
  • 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
  • White Blood Cell Count (WBC) [ Time Frame: day 6 ]
    As assessed via serum blood samples.
  • Platelets Count [ Time Frame: day 6 ]
    As assessed via serum blood samples.
  • Hemogoblin [ Time Frame: day 6 ]
    Measures the total amount of the oxygen-carrying protein in the blood as assessed via serum blood samples.
  • Hematocrit [ Time Frame: day 6 ]
    The percentage by volume of red cells in your blood as assessed via serum blood samples.
  • 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
  • Lymphocytes [ Time Frame: day 6 ]
    Lymphocyte count as assessed via serum blood samples
  • 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.
  • 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.
  • Sodium [ Time Frame: day 6 ]
    Sodium levels as assessed by serum blood samples.
  • Potassium [ Time Frame: day 6 ]
    Potassium levels as assessed via serum blood samples.
  • Creatinine [ Time Frame: day 6 ]
    Creatinine levels as assessed via serum blood samples
  • Glucose [ Time Frame: day 6 ]
    Glucose levels as assessed via serum blood samples
  • Albumin [ Time Frame: day 6 ]
    Albumin levels as assessed via serum blood samples
  • Alkaline Phosphatase [ Time Frame: day 6 ]
    Alkaline phosphatase levels as assessed via serum blood samples for the Comprehensive Metabolic Panel.
  • 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
  • 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
  • Total Bilirubin [ Time Frame: day 6 ]
    Bilirubin levels as assessed via serum blood samples for the comprehensive metabolic panel.
  • Blood Urea Nitrogen (BUN) [ Time Frame: day 6 ]
    Blood urea nitrogen (BUN) levels as assessed via serum blood samples for the comprehensive metabolic panel.
  • Calcium [ Time Frame: day 6 ]
    Calcium levels as assessed via serum blood samples for the comprehensive metabolic panel.
  • Chloride [ Time Frame: day 6 ]
    Chloride levels as assessed via serum blood samples for the comprehensive metabolic panel.
  • Carbon Dioxide (CO2) [ Time Frame: day 6 ]
    Carbon Dioxide (CO2) levels as assessed via serum blood samples for the comprehensive metabolic panel.
  • C-Reactive Protein Levels [ Time Frame: day 6 ]
    As assessed via serum blood samples.
  • Arachidonic Acid/Eicosapentaenoic Acid (AA/EPA) Ratio [ Time Frame: day 6 ]
    As assessed via serum blood samples on day 6 (visit 8).
  • D-dimer Levels [ Time Frame: day 6 ]
    As assessed via serum blood samples.
  • 25-Hydroxy Vitamin D Levels [ Time Frame: day 6 ]
    As assessed via serum blood samples.
  • Tumor Necrosis Factor-alpha (TNFα) [ Time Frame: day 6 ]
    Analysis of TNFα in peripheral blood plasma
  • Tumor Necrosis Factor-beta (TNFβ) [ Time Frame: day 6 ]
    Analysis of TNFβ in peripheral blood plasma
  • Soluble Tumor Necrosis Factor Receptor 2 (sTNFR2) [ Time Frame: day 6 ]
    Analysis of soluble tumor necrosis factor receptor 2 (sTNFR2) in peripheral blood plasma
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2020)
  • Survival [ Time Frame: 90 days ]
    Number of participants that are alive at 90 days post first infusion follow up.
  • Ventilator-Free Days [ Time Frame: 28 days or hospital discharge, whichever is earlier ]
    Number of days participants were off ventilators within up to 28 days of hospitalization
  • Change in Oxygenation Index (OI) [ Time Frame: 28 days ]
    Measure the fraction of inspired oxygen (FiO2) and its usage within the body during intensive care, measured using fNIRS (Functional Near Infrared Spectroscopy).
  • Plat-PEEP [ Time Frame: 28 days ]
    Measuring respiratory mechanics in ventilated patients [plateau pressure (Pplat)-positive end-expiratory pressure]
  • Sequential Organ Failure Assessment (SOFA) Scores [ Time Frame: 28 days ]
    The SOFA assessment 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 0 (normal) to 4 (high degree of dysfunction/failure)
  • Small Identification Test (SIT) scores [ Time Frame: At baseline, day 18 and day 28. ]
    The SIT is a self-administered 40-item test involving microencapsulated (scratch-and-sniff) odors with a forced-choice design. The test has a total score ranging from 0-40 Follows scoring key for evaluation. The higher score indicates better outcome.
  • Troponin I levels [ Time Frame: Baseline, 28 days ]
    As assessed via serum blood samples.
  • C-Reactive Protein levels [ Time Frame: Baseline, 28 days ]
    As assessed via serum blood samples.
  • Arachidonic Acid (AA)/Eicosapentaenoic Acid (EPA) Ratio [ Time Frame: Baseline, 28 days ]
    As assessed via serum blood samples.
  • D-dimer levels [ Time Frame: Baseline, 28 days ]
    As assessed via serum blood samples.
  • 25-Hydroxy Vitamin D levels [ Time Frame: Baseline, 28 days ]
    As assessed via serum blood samples.
  • Alloantibodies levels [ Time Frame: Baseline, 28 days ]
    As assessed via serum blood samples.
  • Blood white cell count [ Time Frame: Baseline, 28 days ]
    As assessed via serum blood samples.
  • Platelets count [ Time Frame: Baseline, 28 days ]
    As assessed via serum blood samples.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Use of UC-MSCs for COVID-19 Patients
Official Title  ICMJE Umbilical Cord-derived Mesenchymal Stem Cells for COVID-19 Patients With Acute Respiratory Distress Syndrome (ARDS)
Brief 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator)
Masking Description:
Double-Blinding Trial
Primary Purpose: Treatment
Condition  ICMJE
  • Corona Virus Infection
  • ARDS
  • ARDS, Human
  • Acute Respiratory Distress Syndrome
  • COVID-19
Intervention  ICMJE
  • Biological: Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.
    UC-MSC will be administered at 100x10^6 cells/infusion administered intravenously in addition to the standard of care treatment.
  • Other: Vehicle + Heparin along with best supportive care
    Best supportive care treatment per the treating hospital protocol.
Study Arms  ICMJE
  • Experimental: UC-MSCs Group
    Participants 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.
    Intervention: Biological: Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.
  • Placebo Comparator: Control Group
    Participants 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.
    Intervention: Other: Vehicle + Heparin along with best supportive care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 17, 2020)		 24
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 31, 2020
Actual Primary Completion Date October 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

  1. Patient currently hospitalized
  2. Aged ≥ 18 years
  3. Willing and able to provide written informed consent, or with a legal representative who can provide informed consent
  4. Peripheral capillary oxygen saturation (SpO2) ≤ 94% at room air, or requiring supplemental oxygen at screening
  5. PaO2/FiO2 ratio < 300 mmHg
  6. Bilateral infiltrates on frontal chest radiograph or bilateral ground glass opacities on a chest CT scan
  7. 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:

  1. PaO2/FiO2 ≥ 300 at the time of enrollment
  2. A previous MSC infusion not related to this trial
  3. History of Pulmonary Hypertension (WHO Class III/IV)
  4. History of left atrial hypertension or decompensated left heart failure.
  5. Pregnant or lactating patient
  6. Unstable arrhythmia
  7. Patients with previous lung transplant
  8. Patients currently receiving chronic dialysis
  9. Patients currently receiving Extracorporeal Membrane Oxygenation (ECMO)
  10. Presence of any active malignancy (except non-melanoma skin cancer)
  11. Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
  12. Moderate to severe liver disease (AST and ALT >5 X ULN)
  13. Severe chronic respiratory disease with a PaCO2 > 50 mm Hg or the use of home oxygen
  14. Baseline QT prolongation
  15. Moribund patient not expected to survive > 24 hours
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04355728
Other Study ID Numbers  ICMJE 20200671
20200370 ( Other Identifier: Secondary Protocol ID )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Camillo Ricordi, University of Miami
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Camillo Ricordi
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Camillo Ricordi, MD University of Miami
PRS Account University of Miami
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP