Use of UC-MSCs for COVID-19 Patients

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04355728
• Other study ID #: 20200671
• Secondary ID: 20200370
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 25, 2020
• Est. completion date: October 31, 2020

Study information

• Verified date: December 2021
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 31, 2020
• Est. primary completion date: October 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• ARDS
• ARDS, Human
• Corona Virus Infection
• Coronavirus Infections
• COVID-19
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
United States	Diabetes Research Institute, University of Miami Miller School of Medicine	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Camillo Ricordi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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: 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	6 and 24 hours
Primary	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).	31 days
Primary	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.	90 days
Primary	Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Total number of adverse events and serious adverse events as assessed by treating physician	90 days
Primary	Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) by Severity	Total number of adverse events plus serious adverse events categorized by severity.	90 days
Primary	Subjects With Adverse Events and Serious Adverse Events by Severity	Total number of subjects with adverse events and serious adverse events categorized by severity.	90 days
Primary	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.	90 days
Primary	Subjects With Adverse Events by Relatedness to Treatment	Total number of subjects with adverse events categorized by relatedness to treatment by a medical professional	90 days
Secondary	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.	31 Days
Secondary	Survival at 60 Days Post First Infusion	Number of participants alive at 60 days post first infusion follow up.	60 days
Secondary	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.	31 days
Secondary	Ventilator-Free Days Throughout 28 Days Post Second Infusion	Number of days participants were off ventilators during 28 days post second infusion.	28 days post second infusion
Secondary	Ventilator-Free Days Throughout 90 Days	Number of days participants were off ventilators within up to 90 days of hospitalization.	90 days or hospital discharge, whichever is earlier
Secondary	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.	day 6
Secondary	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).	day 6
Secondary	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)	day 6
Secondary	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).	Day 6
Secondary	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	90 days
Secondary	White Blood Cell Count (WBC)	As assessed via serum blood samples.	day 6
Secondary	Platelets Count	As assessed via serum blood samples.	day 6
Secondary	Hemogoblin	Measures the total amount of the oxygen-carrying protein in the blood as assessed via serum blood samples.	day 6
Secondary	Hematocrit	The percentage by volume of red cells in your blood as assessed via serum blood samples.	day 6
Secondary	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	day 6
Secondary	Lymphocytes	Lymphocyte count as assessed via serum blood samples	day 6
Secondary	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.	day 6
Secondary	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.	Day 6
Secondary	Sodium	Sodium levels as assessed by serum blood samples.	day 6
Secondary	Potassium	Potassium levels as assessed via serum blood samples.	day 6
Secondary	Creatinine	Creatinine levels as assessed via serum blood samples	day 6
Secondary	Glucose	Glucose levels as assessed via serum blood samples	day 6
Secondary	Albumin	Albumin levels as assessed via serum blood samples	day 6
Secondary	Alkaline Phosphatase	Alkaline phosphatase levels as assessed via serum blood samples for the Comprehensive Metabolic Panel.	day 6
Secondary	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	day 6
Secondary	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	day 6
Secondary	Total Bilirubin	Bilirubin levels as assessed via serum blood samples for the comprehensive metabolic panel.	day 6
Secondary	Blood Urea Nitrogen (BUN)	Blood urea nitrogen (BUN) levels as assessed via serum blood samples for the comprehensive metabolic panel.	day 6
Secondary	Calcium	Calcium levels as assessed via serum blood samples for the comprehensive metabolic panel.	day 6
Secondary	Chloride	Chloride levels as assessed via serum blood samples for the comprehensive metabolic panel.	day 6
Secondary	Carbon Dioxide (CO2)	Carbon Dioxide (CO2) levels as assessed via serum blood samples for the comprehensive metabolic panel.	day 6
Secondary	C-Reactive Protein Levels	As assessed via serum blood samples.	day 6
Secondary	Arachidonic Acid/Eicosapentaenoic Acid (AA/EPA) Ratio	As assessed via serum blood samples on day 6 (visit 8).	day 6
Secondary	D-dimer Levels	As assessed via serum blood samples.	day 6
Secondary	25-Hydroxy Vitamin D Levels	As assessed via serum blood samples.	day 6
Secondary	Tumor Necrosis Factor-alpha (TNFa)	Analysis of TNFa in peripheral blood plasma	day 6
Secondary	Tumor Necrosis Factor-beta (TNFß)	Analysis of TNFß in peripheral blood plasma	day 6
Secondary	Soluble Tumor Necrosis Factor Receptor 2 (sTNFR2)	Analysis of soluble tumor necrosis factor receptor 2 (sTNFR2) in peripheral blood plasma	day 6
Secondary	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).	day 6
Secondary	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.	day 3 post first infusion
Secondary	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.	day 6
Secondary	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.	day 14
Secondary	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.	day 14 post first infusion