Use of UC-MSCs for COVID-19 Patients

Camillo Ricordi24 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Corona Virus Infection ARDS ARDS, Human Acute Respiratory Distress Syndrome COVID-19

Interventions

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Diabetes Research Institute, University of Miami Miller School of Medicine

Miami, Florida, United States

Outcomes

Primary Outcomes

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 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

Time frame: 6 and 24 hours

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).

Time frame: 31 days

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.

Time frame: 90 days

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

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

Time frame: 90 days

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

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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

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.

Time frame: 31 Days

Survival at 60 Days Post First Infusion

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

Time frame: 60 days

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.

Time frame: 31 days

Ventilator-Free Days Throughout 28 Days Post Second Infusion

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

Time frame: 28 days post second infusion

Ventilator-Free Days Throughout 90 Days

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

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

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.

Time frame: day 6

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).

Time frame: day 6

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)

Time frame: day 6

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).

Time frame: Day 6

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

Time frame: 90 days

White Blood Cell Count (WBC)

As assessed via serum blood samples.

Time frame: day 6

Platelets Count

As assessed via serum blood samples.

Time frame: day 6

Hemogoblin

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

Time frame: day 6

Hematocrit

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

Time frame: day 6

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

Time frame: day 6

Lymphocytes

Lymphocyte count as assessed via serum blood samples

Time frame: day 6

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.

Time frame: day 6

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.

Time frame: Day 6

Sodium

Sodium levels as assessed by serum blood samples.

Time frame: day 6

Potassium

Potassium levels as assessed via serum blood samples.

Time frame: day 6

Creatinine

Creatinine levels as assessed via serum blood samples

Time frame: day 6

Glucose

Glucose levels as assessed via serum blood samples

Time frame: day 6

Albumin

Albumin levels as assessed via serum blood samples

Time frame: day 6

Alkaline Phosphatase

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

Time frame: day 6

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

Time frame: day 6

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

Time frame: day 6

Total Bilirubin

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

Time frame: day 6

Blood Urea Nitrogen (BUN)

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

Time frame: day 6

Calcium

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

Time frame: day 6

Chloride

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

Time frame: day 6

Carbon Dioxide (CO2)

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

Time frame: day 6

C-Reactive Protein Levels

As assessed via serum blood samples.

Time frame: day 6

Arachidonic Acid/Eicosapentaenoic Acid (AA/EPA) Ratio

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

Time frame: day 6

D-dimer Levels

As assessed via serum blood samples.

Time frame: day 6

25-Hydroxy Vitamin D Levels

As assessed via serum blood samples.

Time frame: day 6

Tumor Necrosis Factor-alpha (TNFα)

Analysis of TNFα in peripheral blood plasma

Time frame: day 6

Tumor Necrosis Factor-beta (TNFβ)

Analysis of TNFβ in peripheral blood plasma

Time frame: day 6

Soluble Tumor Necrosis Factor Receptor 2 (sTNFR2)

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

Time frame: day 6

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).

Time frame: day 6

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.

Time frame: day 3 post first infusion

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.

Time frame: day 6

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.

Time frame: day 14

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.

Time frame: day 14 post first infusion